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Chemical Structure| 6976-17-6 Chemical Structure| 6976-17-6

Structure of 6976-17-6

Chemical Structure| 6976-17-6

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Product Details of [ 6976-17-6 ]

CAS No. :6976-17-6
Formula : C5H12ClNO2
M.W : 153.61
SMILES Code : O=C(O)CCCNC.Cl
MDL No. :MFCD00012612
InChI Key :JMLHQRQZCMCQNJ-UHFFFAOYSA-N
Pubchem ID :12626654

Safety of [ 6976-17-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 6976-17-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 0
Fraction Csp3 0.8
Num. rotatable bonds 4
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 37.69
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

49.33 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

0.0
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

-1.83
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

0.87
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

0.39
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-0.13
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.14

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

0.62
Solubility 647.0 mg/ml ; 4.21 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Highly soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

1.31
Solubility 3150.0 mg/ml ; 20.5 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Highly soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-0.85
Solubility 21.5 mg/ml ; 0.14 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

Yes
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-8.54 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.05

Application In Synthesis of [ 6976-17-6 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 6976-17-6 ]

[ 6976-17-6 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 872-50-4 ]
  • [ 6976-17-6 ]
YieldReaction ConditionsOperation in experiment
90% With hydrogenchloride; In water; at 165℃; for 13.5h; N-methyl-2-pyrrolidone, concentrated hydrochloric acid, was added to the reaction vessel.The mixture was stirred and refluxed at 165 ° C for 9 hours in an external bath, and concentrated hydrochloric acid was added thereto, followed by stirring under reflux for 4.5 hours.Hydrochloric acid was evaporated under reduced pressure, and the remaining solid was added to cold acetone, stirred and cooled.The solid was crystallized (white solid), frozen to allow complete precipitation, filtered and washed twice with cold acetone.Drain and dry. MP 119-120, after the mother liquor is concentrated and recovered, some products can be obtained. The yield was 90percent.
  • 2
  • [ 50-00-0 ]
  • [ 6976-17-6 ]
  • [ 69954-66-1 ]
  • 3
  • [ 6976-17-6 ]
  • [ 104-12-1 ]
  • 1-(3-carboxypropyl)-3-(4-chlorophenyl)-1-methylurea [ No CAS ]
  • 5
  • [ 75-15-0 ]
  • [ 6976-17-6 ]
  • disodium 4-[carbodithioato(methyl)amino]butanoate [ No CAS ]
  • 6
  • [ 6976-17-6 ]
  • 7-ethyl-2-isopropyl-2-methyl-5H-imidazo[1',2':1,2]pyrrolo[3,4-b]pyridine-3(2H),5-dione [ No CAS ]
  • [ 178612-01-6 ]
  • 7
  • [ 31027-31-3 ]
  • [ 6976-17-6 ]
  • [ 511552-14-0 ]
  • 8
  • [ 89007-45-4 ]
  • [ 6976-17-6 ]
  • 1-(3-carboxypropyl)-3-(4-isopropylphenyl)-1-methylthiourea [ No CAS ]
  • 9
  • [ 6976-17-6 ]
  • [ 103-72-0 ]
  • [ 32265-73-9 ]
  • 10
  • [ 6976-17-6 ]
  • [ 93777-26-5 ]
  • [ 329347-22-0 ]
  • 11
  • [ 67-56-1 ]
  • [ 6976-17-6 ]
  • [ 88061-65-8 ]
YieldReaction ConditionsOperation in experiment
thionyl chloride; at 0℃; for 0.5h; 4- (methylamino) butyric acid Cl was dissolved in methanol and thionyl chlo- ride in catalytic amount was added drop by drop. The reaction mixture was stirred at 0 °C for 30 min. Thereafter, the solvent was reduced in vacu, yielding a white solid.
With hydrogenchloride; at 20℃; Step 1; 4-Methylamino-butyric acid methyl ester; A solution of 2.3 g (15 mmol) 4-Methylamino-butyric acid hydrochloride and 25 mL (31 <n="218"/>mmol) HCl (1.25 M in MeOH) in 150 mL MeOH is stirred overnight at RT. The solvent is removed in vacuo and the residue is used without further purification. MS (method D): 132 [M+H]
  • 12
  • [ 6976-17-6 ]
  • [ 79-22-1 ]
  • [ 756874-13-2 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In 1,4-dioxane; water; at 20℃; for 16.0167h; 4- (Methylamino) butyric acid hydrochloride (5 g, 32.5 mmol), and potassium carbonate (18 g, 130 mmol) were suspended in water (50 ml) and dioxane (25 ml) then cooled to 0 oC. Methyl chloroformate (13 ml, 168 mmol) was added over 1 minute, then the mixture was stirred and allowed to warm slowly to room temperature for 16 hours. Conc. HC1 (20 ML) was added then the mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, evaporated and dried in vacuo to give 4- [ (methoxycarbonyl) (methyl) amino] butyric acid as a thick clear oil (9.7 g).
  • 13
  • 3-Methoxy-2,4-bis(3ethyl-2-benzothiazolinylidenemethyl)-cyclobutenediylium-1-olate methosulphate [ No CAS ]
  • [ 2052-49-5 ]
  • [ 6976-17-6 ]
  • 3-(N-methyl-N-(3-carboxypropyl))amino-2,4-bis(3-ethyl-2-benzothiazolinylidenemethyl)-cyclobutenediylium-1-olate chloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
In methanol; 3-(N-methyl-N-(3-carboxypropyl))amino-2,4-bis(3-ethyl-2-benzothiazolinylidenemethyl)-cyclobutenediylium-1-olate chloride (9d) 4-(Methylamino)butanoic acid.HCl (0.31 g, 2.0 mmol) was dissolved in methanol (10 ml). To this solution was added a solution of tetra-n-butylammonium hydroxide in methanol (1M, 4 ml, 4.0 mmol), followed by dye (9b) (0.58 g, 1.0 mmol). The deep blue solution that resulted was stirred for 40 mins; t.l.c. (silica; 15percent methanol/dichloromethane. (9b), Rf =0.3-->(9d), Rf <0.1). The solvent was removed under reduced pressure and the residue triturated with water. The metallic bronze solid was collected by filtration, washed with water and acetone, then dried under vacuum to give the acid dye (9d), 0.435 g (82percent).
  • 14
  • [ 58053-83-1 ]
  • [ 6976-17-6 ]
  • 4-[(11-acetoxy-6,17-dihydroxy-1-methoxymethyl-10,13-dimethyl-3,7-dioxo-1,7,10,11,12,13,14,15,16,17-decahydro-2-oxa-cyclopenta[a]phenanthren-4-ylidenemethyl)-methyl-amino]-butyric acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In dichloromethane; at 20℃; for 12h; Example 37: Preparation of 4-[(l l-Acetoxy-6,17-dihydroxy- 1 -methoxymethyl- 10, 13- dimethyl-3 ,7-dioxo- 1 ,7, 10, 11 , 12, 13 , 14, 15, 16, 17-decahydro-2-oxa-cyclopenta[a]phenanthren- 4-ylidenemethyl)-methyl-amino] -butyric acid; To a solution of 100 mg (0.23 mmol) 17-hydroxywortmannin and triethylamine (65 muL, 0.46 mmol) in 2 mL CH2Cl2 is added <strong>[6976-17-6]4-(methylamino)butyric acid hydrochloride</strong> (71 mg, 0.46 mmol). The reaction mixture is stirred at room temperature for 12 hours and then concentrated in vacuo. The residue is dissolved in EtOAc and precipitated with hexane. The precipitate is washed two times with hexane to give the product as a yellow solid. MS (ESI) m/z 549 (M+H).
  • 15
  • [ 6976-17-6 ]
  • [ 75-36-5 ]
  • 4-(N-methylacetamido)butanoic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; In sodium hydroxide; 4-(N-Methylacetamido)butanoic acid may be prepared in the following manner: acetyl chloride (11.8 g) is added in the course of 1 hour to a solution, maintained at a temperature in the region of 5° C., of <strong>[6976-17-6]4-(N-methylamino)butanoic acid hydrochloride</strong> (15.4 g) in 2.5N aqueous sodium hydroxide solution (200 cc). The mixture is stirred again for 30 minutes at approximately 5° C. and then acidified to a pH in the region of 1 using 12N aqueous hydrochloric acid solution.
  • 16
  • [ 6976-17-6 ]
  • [ 2004-06-0 ]
  • [ 81893-73-4 ]
YieldReaction ConditionsOperation in experiment
With tributyl-amine; In propan-1-ol; ethanol; EXAMPLE 3 Preparation of N6 -methyl-N6 -(3-carboxypropyl)adenosine A mixture of 10.0 g (34.9 mmole) of 6-chloropurine riboside, 11.0 g (71.6 mmole) of <strong>[6976-17-6]4-(methylamino)butanoic acid hydrochloride</strong>, and 20.0 g (108 mmole) of tributylamine in 300 ml of propanol was heated at reflux for two days. The solution was allowed to cool and concentrated in vacuo to a thick oil. The oil was treated with several portions of diethyl ether to remove soluble organic material. Two crops of crude product were crystallized from ethanol and redissolved in 100 ml of 50percent aqueous ethanol. The resulting solution was decolorized with charcoal, filtered, and the volume was reduced to about 30 ml by boiling. Upon cooling, 4.3 g (11.7) mmole) of N6 -methyl-N6 -(3-carboxypropyl)adenosine was obtained as a fluffy white solid. Anal. Calcd. for C15 H21 N5 O6: C, 49.04; H, 5.76; N, 19.06. Found: C, 48.91; H, 5.83; N, 18.67.
  • 17
  • [ 108-20-3 ]
  • [ 6976-17-6 ]
  • [ 93777-26-5 ]
  • [ 329347-22-0 ]
YieldReaction ConditionsOperation in experiment
86% With hydrogenchloride; sodium carbonate; In hexane; water; dimethyl sulfoxide; Example 1 Synthesis of 4-(4-bromo-2-formyl-N-methylanilino)-butyric acid To a suspension of 5-bromo-2-fluorobenzaldehyde (20.3 g) and <strong>[6976-17-6]4-methylaminobutyric acid hydrochloride</strong> (18.4 g) in DMSO/water(100 ml/100 ml) was slowly add sodium carbonate (25.4 g), followed by stirring at 105°C to 110°C for 3.5 hours. The mixture was cooled to 50°C to 60°C, atwhich temperature 6N hydrochloric acid was added dropwise to adjust the pH to 3. The mixture was extracted with ethyl acetate (200 ml + 100 ml), and the organic layer was washed with a saturated aqueous sodium chloride solution (40 ml * 2) and water (40ml). The organic layer was concentrated, and the concentrate was then dissolved in IPE (50 ml), to which n-hexane (50 ml) was added dropwise. The precipitates were filtered out and washed with IPE/n-hexane (16 ml/4 ml). The filter cake was dried under reduced pressure at room temperature for 4 hours to give 4-(4-bromo-2-formyl-N-methylanilino)butyric acid (25.9 g, 86percent yield) as yellow crystals. 1H-NMR (CDCl3, delta, 300 MHz): 1.95 (2H, tt, J = 6.5, 7.4 Hz), 2.38 (2H, t, J = 6.5 Hz), 2.88 (3H, s), 3.17 (2H, t, J = 7.4 Hz), 7.01 (1H, d, J = 8.7 Hz), 7.55 (1H, dd, J = 8.7, 2.5 Hz), 7.87 (1H, d, J = 2.5 Hz), 10.16 (1H, s).
  • 18
  • [ 24424-99-5 ]
  • [ 6976-17-6 ]
  • [ 94994-39-5 ]
YieldReaction ConditionsOperation in experiment
100% With triethylamine; In dichloromethane; at 20℃; for 72h; Example 12; Preparation of 4-(ter*-Butoxycarbonylmethylamino)butyric Acid To a stirred mixture of <strong>[6976-17-6]4-(methylamino)butyric acid hydrochloride</strong> (1.00 g, 6.51 mmol) and triethylamine (2.72 mL, 19.5 mmol) in DCM (60 mL) at room temperature was added di-tert-butyldicarbonate (1.56 g, 7.16 mmol). The resulting mixture was stirred for about 72 h. LC-MS showed product was present (Rt 4.11 min; m/z 216.2 [M + H]+). DCM and water were added and the pH of the aqueous layer was adjusted to pH 4.5 to 6 with aqueous hydrochloric acid (1 M). The layers were separated and the organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to give the title compound (1.5 g, 100 percent yield) as light yellow thick oil.1H NMR (CDCl3) delta 3.28 (br s); 2.85 (s); 2.35 (t); 1.84 (t); 1.46 (s).
96% With triethylamine; In methanol; at 20℃; for 1.16667h; Di-t-butyl dicarbonate (7 g, 32.1 mmol) was added dropwise over 10 minutes to a mixture of <strong>[6976-17-6]4-(methylamino)butyric acid hydrochloride</strong> (5 g, 32.5 mmole) in MeOH (50 mL) and 3 eq. Et3N (5 mL). The reaction mixture was stirred at room temperature for 1 hour and then concentrated under reduced pressure. The residue was dissolved in EtOAc (150 mL), and washed with an ice-cold 0.1 N aqueous HCl solution (2.x.70 mL). The organic layer was then washed with water (2.x.100 mL) to neutral pH, and then washed with sat. NaCl (1.x.100 mL). The EtOAc layer was dried over Na2SO4 and concentrated to give the Boc-protected product (6.8 g, 96percent yield).
70% [0335] To a stirred solution of <strong>[6976-17-6]4-(methylamino)-butyric acid hydrochloride</strong> (303 mg, 1.97 mmol) and dioxane (2 mL) in saturated aqueous NaHCO3 (2 mL) was added added di-tert-butyl di-carbonate (523 mg, 2.40 mmol) and the mixture was stirred at 0° C. for 20 minutes followed by stirring at room temperature for 22 hours. The reaction was concentrated under reduced pressure and the residue was diluted with water (20 mL). The aqueous phase was extracted with ethyl acetate (2.x.15 mL). The aqueous phase was treated with 5percent w/v aqueous citric acid until a pH of 4 was obtained. The aqueous phase was then again extracted with ethyl acetate (4.x.15 mL). The combined organic phase was dried (MgSO4), filtered and concentrated under reduced pressure to give a colourless oil (300 mg, 70percent). [0336] To a stirred solution of the N-protected acid from above (143 mg, 0.659 mmol) in THF (5 mL) was added BH3.THF (1.0M in THF, 2.5 mmol) and the mixture was stirred at 50° C. for 64 hours. Dry CH3OH (5 mL) was added, and the mixture stirred at 70° C. for 1 hour. The reaction was concentrated under reduced pressure. The crude yellow oil (148 mg) was purified by column chromatography (2 cm OD, 20 g silica, 1:1 EtOAc: hexanes) to afford the N-protected alcohol (71 mg, 53percent). [0337] To a suspension of the N-protected alcohol from above (71 mg, 0.35 mmol), NMO (65 mg, 0.56 mmol) and 3 molecular sieves (186 mg) in CH2Cl2 (2.55 mL) was added TPAP (13 mg, 0.04 mmol) and the mixture was stirred at room temperature for 1 hour. The mixture was filtered through a silica gel plug with ethyl acetate. The filtrate was concentrated under reduced pressure to give a yellow oil (46 mg, 65percent). [0338] Using the General Procedure B: To a stirred solution of the N-protected aldehyde from above (46 mg, 0.229 mmol) and [1-(tert-butyloxycarbonyl)-(1H-benzimidazol-2-ylmethyl)]-(5,6,7,8-tetrahydroquinolin-8-yl)-amine (89 mg, 0.229 mmol) in CH2Cl2 (2.55 mL) was added NaBH(OAc)3 (100 mg, 0.47 mmol) and the mixture was stirred for 19 hours. Purification of the crude yellow oil (126 mg) by flash chromatography (12 g silica, 50:1:1 CH2Cl2: CH3OH: NH4OH) afforded the N-protected tertiary amine (80 mg, 62percent). [0339] Using the General Procedure D: The N-protected tertiary amine from above (76 mg, 0.135 mmol) was converted to COMPOUND 34 as a white solid (71 mg, 75percent). 1H NMR (D2O) delta 1.54 (br s, 4H), 1.74-1.90 (m, 1H), 1.95-2.09 (m, 1H), 2.13-2.23 (m, 1H), 2.32-2.42 (m, 1H), 2.50-2.64 (m, 4H) containing 2.61 (s, 3H), 2.77-2.94 (m, 3H), 2.97-3.04 (m, 2H), 4.39 (d, 1H, J=17.1 Hz), 4.47-4.60 (m, 2H) containing 4.53 (d, 1H, J=17.2 Hz), 7.60 (dd, 2H, J=6.1, 3.0 Hz), 7.80 (dd, 2H, J=6.1, 3.0 Hz), 7.86 (dd, 1H, J=7.9, 6.2 Hz), 8.34 (d, 1H, J=7.9 Hz), 8.62 (d, 1H, J=5.0 Hz). 13C NMR (D2O) delta 20.42 (2 carbons), 23.69, 25.40, 27.64, 33.05, 48.23, 49.00, 51.68, 60.66, 114.25 (2 carbons), 125.93, 126.93 (2 carbons), 130.97, 139.31, 140.61, 148.10, 151.25, 151.77. ES-MS m/z 364 (M+H). Anal Calc. for C21H25N5O.3.2HBr.1.9H2O: C, 38.41; H, 4.91; N, 10.67; Br, 38.94. Found: C, 38.53; H, 5.02; N, 10.42; Br, 38.79.
a) 4-(N-tert-Butoxycarbonyl-N-methylamino)butyric acid Using <strong>[6976-17-6]4-(N-methylamino)butyric acid hydrochloride</strong> (23 g, 150 mmol) and di-tert-butyl dicarbonate (32.7 g, 150 mmol), the title compound was obtained as an oil according to the method of Example 1(a) (31 g, yield: 95percent).
With triethylamine; In tetrahydrofuran; at 25℃; A solution of <strong>[6976-17-6]4-(methylamino)butyric acid hydrochloride</strong> (2.0 g, 13.0 mmol) in 25 mL of THF at 25° C. was treated with Boc2O (4.3 g, 19.5 mmol) and Et3N (7.3 mL, 52.0 mmol), and the mixture was stirred overnight before being quenched with the addition of 40 mL of aqueous 1N NaOH. The mixture was washed with CH2Cl2 (2.x.100 mL), cooled to 0° C., acidified (pH 5-6) with the addition of aqueous 3.5 N HCl, and extracted with CH2Cl2 (2.x.75 mL). The combined organic extracts were dried (MgSO4) and concentrated under reduced pressure to give 4-[[(1,1-dimethylethyl)oxy]carbonyl}(methyl)amino]butanoic acid as a white solid.
With potassium carbonate; In 1,4-dioxane; water; for 6h; 3 g of <strong>[6976-17-6]4-(methylamino)butyric acid hydrochloride</strong>, 7 g of potassium carbonate in 40 mL of 1,4-dioxane and 20 mL of water are placed in a round-bottomed flask. Next, 4.86 g of di-tert-butyl dicarbonate are added. After stirring for 6 hours, the dioxane is evaporated off and 30 mL of water are then added. Aqueous 1 M potassium bisulfate solution is added until pH 2 is obtained. The resulting mixture is extracted twice with 10 mL of ethyl acetate, dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure. 4.37 g of 4-(tert-butoxycarbonylmethylamino)butyric acid are obtained.

  • 19
  • [ 6976-17-6 ]
  • [ 94994-39-5 ]
YieldReaction ConditionsOperation in experiment
a) 4-(N-tert-Butyloxycarbonyl-N-methylamino)butyric acid Using <strong>[6976-17-6]4-methylaminobutyric acid hydrochloride</strong> (30 g, 200 mmol), a reaction was performed in the same manner as described in Example 1 (a) to obtain the title compound as an oil (44.08 g, quantitative). 1H-NMR (CDCl3): 3.28 (t, 2H), 2.85 (s, 3H) 2.36 (t, 2H), 1.85 (m, 2H), 1.45 (s, 9H)
  • 20
  • [ 64-17-5 ]
  • [ 6976-17-6 ]
  • ethyl 4-(methylamino)-butanoate hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
100% hydrogenchloride; In diethyl ether; at 70℃; for 20h; Part C. Preparation of Ethyl-4-(methylamino)butyrate hydrochloride HI; 4-(Methylamino)butyric acid hydrochloride (7.5 g, 49 mmol, Aldrich) was dissolved in 75 mL of absolute ethanol and 4 mL of 2.0 M HCl in ether (Aldrich) was added. The solution, which became clear upon heating to 70 °C, was refluxed for 20 hours. The solvent was removed in vacuo resulting in a white, solid, hydrochloride salt in quantitative yield. 1HNMR (300 MHz, CDCl3) delta 1.20 (t, J=7.2 Hz, 3H), 2.13 (m, 2H), 2.47 (t , J=7.2 Hz, 2H)5 2.67 (t, J=5.7 Hz, 3H), 3.00 (broad m, 2H), 4.07 (q, J=7.2 Hz, 2H), 9.50 (broad s, 2H).
sulfuric acid; at 90℃; for 1h; [Example 72] 4-[[((2S)-1'-{2-[(2R)-4-[3,5-bis(Trifluoromethyl)benzoyl]-2-(3,4-dichlorophenyl)morpholin-2-yl]ethyl}-2,3-dihydrospiro[indene-1,4'-piperidin]-2-yl)oxy]acetyl}(methyl)amino]butanoic acid hydrochloride (Exemplary compound No. 2-495 hydrochloride) [Example 72a] Ethyl 4-(methylamino)butanoate hydrochloride 2.00 g (13.0 mmol) of <strong>[6976-17-6]4-(methylamino)butanoic acid hydrochloride</strong> was dissolved in 40 mL of ethanol and 69 muL (1.30 mmol) of concentrated sulfuric acid was added thereto, followed by stirring of the mixture at 90°C for 1 hour. The solvent was distilled off under reduced pressure, followed by azeotropy with toluene. 3.02 g of the obtained residue was used for the subsequent reaction as such. 1H-NMR spectrum (400 MHz, CD3OD) delta ppm: 4.14 (2H, q, J=7.2Hz), 3.03 (2H, t, J=7.6Hz), 2.69 (3H, s), 2.47 (2H, t, J=7.0Hz), 1.99-1.90 (2H, m), 1.25 (3H, t, J=7.2Hz).
  • 21
  • BH3.THF [ No CAS ]
  • [ 405058-36-8 ]
  • [ 51300-90-4 ]
  • [ 6976-17-6 ]
  • [ 757938-98-0 ]
YieldReaction ConditionsOperation in experiment
With N-methyl-2-indolinone; tetrapropylammonium perruthennate; NaBH(OAc)3;molecular sieves; In tetrahydrofuran; 1,4-dioxane; methanol; dichloromethane; sodium hydrogencarbonate; Example 34 Compound 34: (1H-Benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydroquinolin-8-yl)-(N-methyl-4-amino-but-1-yl)-amine To a stirred solution of <strong>[6976-17-6]4-(methylamino)-butyric acid hydrochloride</strong> (303 mg, 1.97 mmol) and dioxane (2 mL) in saturated aqueous NaHCO3 (2 mL) was added added di-tert-butyl di-carbonate (523 mg, 2.40 mmol) and the mixture was stirred at 0° C. for 20 minutes followed by stirring at room temperature for 22 hours. The reaction was concentrated under reduced pressure and the residue was diluted with water (20 mL). The aqueous phase was extracted with ethyl acetate (2*15 mL). The aqueous phase was treated with 5percent w/v aqueous citric acid until a pH of 4 was obtained. The aqueous phase was then again extracted with ethyl acetate (4*15 mL). The combined organic phase was dried (MgSO4), filtered and concentrated under reduced pressure to give a colourless oil (300 mg, 70percent). To a stirred solution of the N-protected acid from above (143 mg, 0.659 mmol) in THF (5 mL) was added BH3.THF (1.0M in THF, 2.5 mmol) and the mixture was stirred at 50° C. for 64 hours. Dry CH3OH (5 mL) was added, and the mixture stirred at 70° C. for 1 hour. The reaction was concentrated under reduced pressure. The crude yellow oil (148 mg) was purified by column chromatography (2 cm OD, 20 g silica, 1:1 EtOAc: hexanes) to afford the N-protected alcohol (71 mg, 53percent). To a suspension of the N-protected alcohol from above (71 mg, 0.35 mmol), NMO (65 mg, 0.56 mmol) and 3A molecular sieves (186 mg) in CH2Cl2 (2.55 mL) was added TPAP (13 mg, 0.04 mmol) and the mixture was stirred at room temperature for 1 hour. The mixture was filtered through a silica gel plug with ethyl acetate. The filtrate was concentrated under reduced pressure to give a yellow oil (46 mg, 65percent). Using the General Procedure B: To a stirred solution of the N-protected aldehyde from above (46 mg, 0.229 mmol) and [1-(tert-butyloxycarbonyl)-(1H-benzimidazol-2-ylmethyl)]-(5,6,7,8-tetrahydroquinolin-8-yl)-amine (89 mg, 0.229 mmol) in CH2Cl2 (2.55 mL) was added NaBH(OAc)3 (100 mg, 0.47 mmol) and the mixture was stirred for 19 hours. Purification of the crude yellow oil (126 mg) by flash chromatography (12 g silica, 50:1:1 CH2Cl2: CH3OH: NH4OH) afforded the N-protected tertiary amine (80 mg, 62percent). Using the General Procedure D: The N-protected tertiary amine from above (76 mg, 0.135 mmol) was converted to COMPOUND 34 as a white solid (71 mg, 75percent).
  • 22
  • [ 82911-69-1 ]
  • [ 6976-17-6 ]
  • N-(Fmoc),N-methyl-γ-aminobutyric acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
<Synthesis of Ia, Ig and Ic>7.68 g (50 mmol) of N-methylamino butyric acid hydrochloride was dissolved in 50 mL of water, 4.20 g (50 mmol) of NaHCO3 was added, and all of these were agitated for 10 min. This solution was agitated for two days at room temperature, with 13.49 g (40 mmol) of 9-fluorenylmethyl succinimidyl carbonate, 100 mL of acetonitrile and 0.14 g (0.4 mmol) of tetrabutylammonium hydrogen sulfide added. After being concentrated under reduced pressure, the solution was diluted with methylene chloride and washed with water. After being concentrated under reduced pressure and subjected twice to azeotropy with dehydrated acetonitrile, the methylene chloride solution was subjected to azeotropy with dehydrated methylene chloride. A residue was dissolved in 200 mL of dehydrated methylene chloride, 4.13 g (20 mmol) of N,N'-dicyclohexylcarbodiimide was added at 0° C., and all of these were agitated for 2 hr at room temperature. After unnecessary materials were filtered out, this solution was concentrated under reduced pressure, and a residue A was obtained.A deoxynucleoside (dA, dG or dC, 20 mmol) was suspended in dehydrated pyridine, and these were concentrated under reduced pressure three times. A residue was suspended in 100 mL of dehydrated pyridine, 8.45 mL (66 mmol) of trimethylchlorosilane was added at 0° C., all of these were agitated for 1 hr at room temperature and then cooled to 0° C. again, and this solution was introduced into the residue A. A reaction mixture was agitated for 2 hr at room temperature. With 20 mL of water added under ice-cold conditions, the reaction mixture was then agitated overnight at room temperature. This solution was diluted with methylene chloride and washed with water. The methylene chloride solution was concentrated under reduced pressure, and a residue was purified by medium-pressure chromatography (dichloromethane-ethanol 19:1 --> 4:1) to yield desired products: 6.91 g (60percent) of Ia, 9.43 g (80percent) of Ig and 8.80 g (80percent) of Ic.
  • 23
  • [ 24424-99-5 ]
  • [ 6976-17-6 ]
  • [ 18107-18-1 ]
  • [ 133171-74-1 ]
YieldReaction ConditionsOperation in experiment
78% 4-(Methylamino)butyric acid hydrochloride (1.0 g, 6.51 mmol) and di-tert-butyl dicarbonate (1.797 mL, 7.81 mmol) were stirred in dioxane (50 mL) and water (10 mL) containing triethylamine (1.361 mL, 9.77 mmol) at 23° C. for 3 h. The solvent was evaporated. The residue was dissolved in EtOAc and washed with 5percent KHSO4, brine and dried over anhydrous Na2SO4. The solvent was evaporated. The residue was then dissolved in methanol (50.0 mL) at 0° C. and (trimethylsilyl)diazomethane (9.77 mL, 19.53 mmol) was added dropwise to the stirring solution until a light yellow color persisted. The solution was then stirred at 23° C. for 15 min. The solvent was evaporated. The residue was dissolved in EtOAc and washed with 5percent KHSO4, aqueous saturated NaHCO3, brine and dried over anhydrous Na2SO4. The product was purified by flash chromatography using a gradient: 20percent to 50percent EtOAc/heptane. Yield: 1.17 g (78percent); 1H NMR (400 MHz, CHLOROFORM-D) delta 1.45 (s, 9H), 1.84 (ddd, J=14.26, 7.42, 7.23 Hz, 2H), 2.32 (t, J=7.42 Hz, 2H), 2.84 (s, 3H), 3.25 (t, J=6.84 Hz, 2H), 3.68 (s, 3H); MS (ESI) (M+H)+=232.23.
  • 24
  • [ 1493-13-6 ]
  • [ 6976-17-6 ]
  • [ 100-66-3 ]
  • [ 1155866-89-9 ]
  • 25
  • [ 777-44-6 ]
  • [ 6976-17-6 ]
  • [ 85845-50-7 ]
YieldReaction ConditionsOperation in experiment
71% With potassium hydroxide; In tetrahydrofuran; water; at 0 - 20℃;Cooling with ice; Synthesis of the Acid Unit AC-13: 4-[Methyl-[[3-(trifluoromethyl)phenyl]sulfonyl]-amino]-butyric acid (AC-13) 4-(Methylamino)butanoic acid hydrochloride (10, 15.1 g, 98.1 mmol) was added to a solution of KOH (16.5 g, 294 mmol) in H2O (75 ml) and the reaction mixture was cooled in an ice bath. A solution of 3-(trifluoromethyl)benzenesulfonyl chloride (9, 12.0 g, 49.1 mmol) in THF (75 ml) was added dropwise to the reaction mixture and the mixture was stirred at room temperature overnight. Aqueous 6 M HCl (75 ml) was added, while cooling with an ice bath, and the addition of CH2Cl2 then followed. The organic phase was separated, washed with sat. NaCl solution, dried over Na2SO4 and concentrated and the residue was co-evaporated with a minimal amount of diethyl ether. Recrystallization of the residue from ethyl acetate/heptane gave AC-13 (11.32 g, 71percent).
71% Synthesis of Acid Building Block S-13; 4-[Methyl-[[3-(trifluoromethyl)phenyl]sulfonyl]-amino]-butyric acid (S-13) To a solution of KOH (16.5 g, 294 mmol) in H2O (75 ml) was added <strong>[6976-17-6]4-(methylamino)butyric acid hydrochloride</strong> (10, 15.1 g, 98.1 mmol) and the reaction mixture was cooled with an icebath. A solution of 3-(trifluoromethyl)benzene-sulfonyl chloride (9, 12.0 g, 49.1 mmol) in THF (75 ml) was dropwise added to the reaction mixture and stirring was continued at room temperature overnight. Aqueous 6 M HCl (75 ml) was added to the reaction mixture while cooling with an icebath, after which CH2Cl2 was added. The organic layer was separated, washed with brine, dried (Na2SO4), concentrated and co-evaporated with a minimal amount of Et2O. Crystallization of the residue out of EtOAc/heptane resulted in S-13 (11.32 g, 71percent).
71% To a solution of KOH (16.5 g, 294 mmol) in H2O (75 mL) was added 4- (methylamino)butyric acid hydrochloride (10, 15.1 g, 98.1 mmol) and the reaction mixture was cooled with an icebath. A solution of 3-(trifluoromethyl)benzenesulphonyl chloride (9, 12.0 g, 49.1 mmol) in THF (75 mL) was dropwise added to the reaction mixture and stirring was continued at room temperature overnight. Aqueous 6 M HCI (75 mL) was added to the reaction mixture while cooling with an icebath, after which CH2CI2 was added. The organic layer was separated, washed with brine, dried (Na2SO4), concentrated and co-evaporated with a minimal amount of Et2O. Crystallization of the residue out of EtOAc/heptane resulted in 11 (11.32 g, 71 percent)
  • 26
  • [ 6976-17-6 ]
  • [ 80745-07-9 ]
  • [ 85845-50-7 ]
YieldReaction ConditionsOperation in experiment
71% With potassium hydroxide; In tetrahydrofuran; water; at 20℃;Cooling with ice; Synthesis of acid building block AC-08: 4-[Methyl-[[3- (trifluoromethyl)phenyl]sulfonyl]-amino]-butyric acid (AC-08)° 9 To a solution of KOH (16.5 g, 294 mmol) in H2O (75 ml) was added 4- (methylamino)butyric acid hydrochloride (10, 15.1 g, 98.1 mmol) and the reaction mixture was cooled with an icebath. A solution of 3-(trifluoromethyl)benzenesulphonyl chloride (9, 12.0 g, 49.1 mmol) in THF (75 ml) was dropwise added to the reaction mixture and stirring was continued at room temperature overnight. Aqueous 6 M HCI (75 ml) was added to the reaction mixture while cooling with an icebath, after which CH2CI2 was added. The organic layer was separated, washed with brine, dried (Na2SO4), concentrated and co-evaporated with a minimal amount of Et2O. Crystallization of the residue out of EtOAc/heptane resulted in AC-08 (11.32 g, 71percent).
  • 27
  • [ 6976-17-6 ]
  • [ 124-40-3 ]
  • tris(2,4,6-trimethoxyphenyl)methyl carbenium tetrafluoroborate [ No CAS ]
  • BF4(1-)*C34H46N3O8(1+) [ No CAS ]
YieldReaction ConditionsOperation in experiment
74% 4a (BF4-) : 4- (METHYLAMINO) butyric acid hydrochloride (1.36 G ; 8.8 MMOL), 1 (5.0 G ; 8.3 MMOL), and diisopropylethylamine (5 mL) is dissolved in acetonitrile (120 mL). The reaction mixture is stirred at 30-35 °C in a dye nitrogen atmosphere for 22 h. Aque- ous DIMETHYLAMINE (40 mL of a 40percent solution) is added and the reaction mixture is stirred for four more days. Solvent and excess dimethyl amine is removed in vacuo and the reminiscent material dissolved in chloroform. The chloroform solution was washed twice with brine and dried over MGS04 before evaporation of the solvent and reprecipitation from CH2CI2/ETHER. Yield : 4.4 G (74percent) dark powder. MS (FAB+): M/Z 624 (M+) 'H-NMR (400 MHz, d6-DMSO): 8 8.34 (1H, s), 6.03 (2H, s), 5.83 (4H, s), 3.49 (2H, m), 3.46 (6H, s), 3.44 (12H, s), 3.12 (3H, s), 3.08 (12H, s), 1.94 (2H, t), 1.70 (2H, m).
70% 4a (BF4-) : 4- (methylamino) butyric acid hydrochloride (1. 36 g; 8.8 mmol), 1 (5. 0 g ; 8.3 mmol), and diisopropylethylamine (5 mL) was dissolved in acetonitrile (120 mL). The reaction mixture was stirred at 30-35 °C in a dry nitrogen atmosphere for 22 h. Aqueous dimethylamine (40 mL of a 40percent solution) was added and the reaction mixture was stirred for four more days. Solvent and excess dimethylamine were removed in vacuo and the remaining material dissolved in chloroform. The chloroform solution was washed twice with brine and dried over MgSO4 before evaporation of the solvent and reprecipitation of the product from CH2Cl2/ether. Yield: 4.4 g (70percent) of a dark blue powder. MS (FAB+): m/z 624 (M+) H-NMR (400 MHz, DMSO-d6) 8. 34. (1H, bs), 6.03 (2H, s), 5. 83 (4H, s), 3,49 (2H, m), 3. 46 (6H, s), 3.44 (12H, s), 3.12 (3H, s (masked)), 3.08 (12H, s), 1. 94 (2H, t), 1.70 (2H, m).
  • 28
  • [ 107-68-6 ]
  • [ 6976-17-6 ]
  • C36H48N3O14S2(1-)*Na(1+) [ No CAS ]
YieldReaction ConditionsOperation in experiment
18% 4c (Na') (method A) : A solution of 4- (methylamino) butyric acid hydrochloride (0. 275 g ; 1.8 mmol), 1 (1.0 g; 1.7 mmol), and diisopropylethylamine (1 mL) in DMSO (25 mL) was stirred for 20 h. at room temperature before sodium N-methyltaurine (2.0 g, 12 mmol), diisopropylethylamine (1 mL) and DMSO (20 mL) was added. The reaction mixture was then stirred for two days at about 70 °C and two days at room temperature. The reaction mixture was filtered through silica followed by thoroughly washing with methanol. The blue filtrate was concentrated and the crude product precipitated, as a sticky blue wax, by addition of ethyl acetate. Column chromatography (silica, MeCN/MeOH 5: 2) gave a blue solid (first blue fraction/band), which was further purified by dissolution in hot ethanol followed by filtration (hot). After cooling the ethanol solution was filtered again and the precipitate was washed with ethanol (leaving a white material). The blue ethanol solution was evaporated yielding 0. 3 g of 4c (18percent). MS (FAB+, Glycerol): m/z 812 (MH2+), 834 (MNaH+), 856 (MNa2+) H-NMR (CD30D, int. solvent ref 3.35 ppm): 8 5.98 (6H, s), 3.95 (4H, t), 3.62 (2H, t), 3.57 (6H, s), 3.56 (12H, s), 3.21 (3H, s), 3. 20 (6H, s), 3.15 (4H, t), 2.41 (2H, t), 1.99 (2H, m).
  • 29
  • [ 910800-57-6 ]
  • [ 6976-17-6 ]
  • [ 765-30-0 ]
  • 5-methyl-2-(tetrahydro-2H-pyran-4-yl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-carboxylic acid [4-(cyclopropylamino)-4-oxobutyl](methyl)amide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Example 1 N- [4-(Cyclopropylamino)-4-oxobutyl] -iV^-dimethyl^-^etrahydro-lH-pyran-^ yl)-2,3,4,5-tetrahydro-lH-pyrido[4,3-L]indole-8-carboxamideStep A: ?ir-[4-(Cyclopropylamino)-4-oxobutyl]-iV,5-dimethyl-2-(tetrahydro-2J3r- pyran-4-yI)-2,3,4,5-tetrahydro-lH-pyrido[4,3-6]indoIe-8-carboxamideHATU(146 mg, 0.38 mmol) was added portionwise into a mixture of 5-methyl-2- (tetrahydro-2H-pyran-4-yl)-2,3,4,5-tetrahydro-lH-pyrido[4,3-?]indole-8-carboxylic acid (100 mg, 0.32 mmol) (see following steps B, C, D, E, F, G, and ? for its preparation), 4-(methylamino) butyric acid hydrochloride (50 mg, 0.32 mmol) and NN-diisopropylethylamine (0.3 uL, 1.3 mmol) in dry DMF (5 mL) at 0 C. The reaction was stirred at room temperature for 2 hours, followed by addition of cyclopropylamine (37 mg, 0.64 mmol) and ?ATU (146 mg, 0.38 mmol). After stirred overnight, the reaction mixture was concentrated, extracted with EtOAc, washed with water then brine. The crude product was purified by LCMS using high p? column 40-65percent acetonitrile gradient to give the title compound as a white solid (TFA salt, 20 mg, 37percent). 1H ?MR (400 MHz, METHA?OL-D4) ? 0.09 - 0.19 (m, 2 H) 0.35 - 0.41 (m, 2 H) 1.73 - 1.93 (m, 6 H) 2.05 - 2.13 (m, 1 H) 2.89 - 3.02 (m, 3 H) 3.12 - 3.19 (m, 3 H) 3.35 - 3.53 (m, 6 H) 3.64 (s, 6 H) 4.03 (dd, J=I 1.72, 4.30 Hz, 4 H) 7.37 (s, 2 H) 7.40 (s, 1 H); MS (APPI) (M+H)+=453.3
  • 30
  • [ 6976-17-6 ]
  • [ 501-53-1 ]
  • [ 98008-66-3 ]
  • 31
  • [ 67-56-1 ]
  • [ 6976-17-6 ]
  • methyl 4-(methylamino)butanoate hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
95% The freshly distilled thionyl chloride was added dropwise to 1500 ml of absolute ethanol while stirring at an external temperature of -18°C.Maintaining the internal temperature does not exceed -3 °C, about 3.5 hours after the completion of the addition, after adding 4-methylamino butyrate, the internal temperature of 25 °C,The reaction was stirred for 18 hours under a dry system. The methanol was distilled off under reduced pressure and absolute ethanol was added to dissolve the residue.Anhydrous ethyl ether was then added, and the crystals were freeze-crystallized in a freezer overnight, filtered, washed three times with a crystallization solution, and dried to give a white solid, MP 73-75°C, yield 95percent.
88% With thionyl chloride; at 20℃; for 24h;Cooling with ice; 4-(Methylamino)butanoic acid hydrochloride (22.1 g, 144 mmol) was dissolved in methanol (560 mL), thionyl chloride (42 mL) was added under ice cooling, and then the mixture was stirred at room temperature for 24 hours. After the reaction was completed, the solvent was evaporated under reduced pressure, and the resulting white solid was washed with a mixed solvent of dichloromethane (30 mL) and hexane (300 mL) to give the title compound (21.2 g; yield, 88percent) as a white solid. 1H NMR (CDCl3, 400 MHz): delta 2.13-2.29 (2H, m), 2.53 (2H, t, J=7.04 Hz), 2.65-2.79 (3H, m), 3.00-3.12 (2H, m), 3.69 (3H, s), 9.32-9.83 (2H, m). MS (EI) m/z: 131 (M)+ (free form). IR (KBr) numax 2962, 1735, 1456, 1427, 1286, 1211, 1017, 895, 884, 752 cm-1.
  • 32
  • [ 6976-17-6 ]
  • [ 107-18-6 ]
  • [ 1404106-33-7 ]
YieldReaction ConditionsOperation in experiment
100% With chloro-trimethyl-silane; at 20℃;Inert atmosphere; N-Methyl-g-aminobutyric acid hydrochloride salt, (143 mg, 0.931 mmol), chlorotrimethylsilane, (155 mg, 1.43 mmol) and allyl alcohol, (815 mg, 14.0 mmol) was stirred at room temperature overnight and then concentrated under reduced pressure to give 180 mg (quant.) of II as white solid. Compound II was used without purification. 1H-NMR (CDCl3) delta (ppm) 9.23 (bs, 2H),5.77-5.64 (m, 1H), 5.16-5.08 (m, 1H), 5.07-5.01 (m, 1H), 4.43-4.33 (m, 2H),2.97-2.81 (m, 2H), 2.53 (t, J = 5.4 Hz, 3H), 2.36 (t, J = 7.2 Hz,2H), 2.06-1.93 (m, 2H); 13C-NMR (CDCl3) delta (ppm) 171.5,131.7, 118.2, 65.1, 48.2, 32.7, 30.7, 20.8; IR l (cm-1)2764, 1734, 1188
  • 33
  • C20H22N2O3 [ No CAS ]
  • [ 82911-69-1 ]
  • [ 6976-17-6 ]
  • [ 1036758-20-9 ]
YieldReaction ConditionsOperation in experiment
60% 7.68 g (50 mmol) of N-methylaminobutyrate hydrochloride was dissolved in 50 mL of water and 4.20 g (50 mmol) of NaHCO3 was added thereto and agitated for 10 minutes. Then, 13.49 g (40 mmol) of 9-fluorenylmethyl succinimidyl carbonate, 100 mL of acetonitrile and 0.14 g (0.4 mmol) tetrabutylammonium hydrogen sulfate were added to the solution and agitated at room temperature for 2 days. After concentrating the solution under reduced pressure, it was diluted by methylene chloride and washed with water. The methylene chloride solution was then concentrated under reduced pressure and subjected to azeotropy by means of dehydrated acetonitrile and then by means of dehydrated methylene chloride. The residue was dissolved in 200 mL of dehydrated methylene chloride and 4.13 g (20 mmol) of N,N?-dicyclohexylcarbodiimide was added and agitated at room temperature for 2 hours. After filtering the undissolved substance, the solution was concentrated under reduced pressure to obtain residue A. Dioxynucleoside (dA, dG or dC, 20 mmol) was suspended in dehydrated pyridine and an operation of concentrating it under reduced pressure was repeated three times. The residue was suspended in 100 mL of dehydrated pyridine and 8.45 mL (66 mmol) of trimethylchlorosilane was added thereto at 0° C. Then, the mixture solution was agitated at room temperature for 1 hour and subsequently cooled to 0° C. again before it was introduced to the residue A. The reaction mixture was agitated at room temperature for 2 hours. Then, 20 mL of water was added to the reaction mixture while the latter was being cooled with ice and the solution was agitated at room temperature overnight. The solution was diluted by methylene chloride and washed with water. The methylene chloride solution was concentrated under reduce pressure and the residue was purified by medium pressure chromatography (dichloromethane-ethanol 19:1?4:1) to obtain target products Ia, Ig and Ic in amounts of 6.91 g (60percent), 9.43 g (80percent) and 8.80 g (80percent), respectively.
  • 34
  • [ 24324-17-2 ]
  • [ 6976-17-6 ]
  • [ 104-15-4 ]
  • [ 1443827-27-7 ]
  • 35
  • [ 506-68-3 ]
  • [ 6976-17-6 ]
  • [ 1443827-24-4 ]
 

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