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Chemical Structure| 61477-39-2 Chemical Structure| 61477-39-2

Structure of 61477-39-2

Chemical Structure| 61477-39-2

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Product Details of [ 61477-39-2 ]

CAS No. :61477-39-2
Formula : C4H11NO
M.W : 89.14
SMILES Code : C[C@H](N)CCO
MDL No. :MFCD08275763
InChI Key :AGMZSYQMSHMXLT-BYPYZUCNSA-N
Pubchem ID :9942121

Safety of [ 61477-39-2 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H314
Precautionary Statements:P280-P301+P330+P331-P302+P352-P304+P340-P305+P351+P338-P310
Class:8
UN#:2735
Packing Group:

Computational Chemistry of [ 61477-39-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 6
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 2.0
Molar Refractivity 25.21
TPSA ?

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

46.25 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.21
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

-0.61
Log Po/w (WLOGP)?

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

-0.28
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.

-0.18
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

-0.43
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.06

Water Solubility

Log S (ESOL):?

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

0.12
Solubility 118.0 mg/ml ; 1.33 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.

0.11
Solubility 115.0 mg/ml ; 1.29 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

-0.09
Solubility 72.1 mg/ml ; 0.809 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

No
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.

-7.28 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

2.0
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)

1.0

Application In Synthesis of [ 61477-39-2 ]

* 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 [ 61477-39-2 ]

[ 61477-39-2 ] Synthesis Path-Downstream   1~25

  • 1
  • [ 61477-38-1 ]
  • [ 61477-39-2 ]
  • 2
  • [ 5303-65-1 ]
  • [ 61477-39-2 ]
  • [ 61477-40-5 ]
  • 3
  • (S)-3-(diphenylmethylamino)butanol [ No CAS ]
  • [ 101-81-5 ]
  • [ 61477-39-2 ]
  • 4
  • [ 61477-39-2 ]
  • [ 118715-67-6 ]
  • C56H72N6O12 [ No CAS ]
  • 5
  • [ 6078-06-4 ]
  • [ 61477-39-2 ]
  • 6
  • [ 50-00-0 ]
  • [ 61477-39-2 ]
  • [ 1088884-57-4 ]
  • 8
  • [ 168827-91-6 ]
  • [ 61477-39-2 ]
YieldReaction ConditionsOperation in experiment
92% With palladium on activated charcoal; hydrogen; In methanol; at 25℃; for 12h; Into a 1000-mL round-bottom flask was placed a solution of benzyl N-[(25)-4-hydroxybutan-2- yljcarbamate (30 g, 134.4 mmol, 1.00 equiv) in methanol (500 mL) and palladium carbon (3 g, 0.10 equiv). The resulting solution was stirred at 25°C for 12 h under an atmosphere of hydrogen. The solids were filtered out and the filtrate was concentrated under vacuum to afford 11.7 g (92percent) of (3S)-3-aminobutan-l-ol as an oil. 1H NMR (300MHz, OMSO, ppm): delta 4.48 (3H, s), 3.47 (2H, s), 2.96 (1H, s), 1.47-1.41 (2H, q), 1.02-0.99 (3H, d); LCMS (ESI), m/z, 90 [M+H] +; measured [a]D2a2 +11.65° (C=1.22g/100mL in EtOH), lit. [a]D2° +16.3° (c=4.5 in EtOH) (J. Org. Chem. 1996, 61, 2293-2304.).
92% With palladium on activated charcoal; hydrogen; In methanol; at 25℃; for 12h; Into a 1000-mL round-bottom flask was placed a solution of benzyl N-[(2S)-4-hydroxybutan-2- yllcarbamate (30 g, 134.4 mmol, 1.00 equiv) in methanol (500 mL) and palladium carbon (3 g, 0.10 equiv). The resulting solution was stirred at 25°C for 12 h under an atmosphere of hydrogen. The solids were filtered out and the filtrate was concentrated under vacuum to afford 11.7 g(92percent) of (3S)-3-aminobutan-1-ol as an oil. ?H NMR (300MHz, DMSO, ppm): oe 4.48 (3H, s), 3.47 (2H, s), 2.96 (1H, s), 1.47-1.41 (2H, q), 1.02-0.99 (3H, d); LCMS (ESI), mlz, 90 [M+Hj measured [cL1D202 +11.650 (C=1.22gIlOOmL in EtOH), lit. [ctlD2° +16.3° (c=4.5 in EtOH) (J. Org. Chem. 1996, 61, 2293?2304.).Using the above procedure, 12.0 g 12 g (94percent) of (3R)-3-aminobutan-1-ol was isolated as an oil. ?H NMR (300MHz, DMSO, ppm): oe 4.48 (3H, s), 3.47 (2H, s), 2.96 (1H, s), 1.47-1.41 (2H, q), 1.02-0.99 (3H, d); LCMS (ESI), mz, 90 [M+Hj measured [ct1D202 -11.1° (C = 0.32g/lOOmL in EtOH), lit. [ct1D25 -25° (c=1.25 in EtOH) (Tetrahedron: Asymmetry 1999, 10, 2213?2224.).
92% With palladium on activated charcoal; hydrogen; In methanol; at 25℃; for 12h; Into a 1000-mL round-bottom flask was placed a solution of benzyl N-[(2S)-4-hydroxybutan-2-yl]carbamate (30 g, 134.4 mmol, 1.00 equiv) in methanol (500 mL) and palladium carbon (3 g, 0.10 equiv). The resulting solution was stirred at 25° C. for 12 h under an atmosphere of hydrogen. The solids were filtered out and the filtrate was concentrated under vacuum to afford 11.7 g (92percent) of (3S)-3-aminobutan-1-ol as an oil. 1H NMR (300 MHz, DMSO, ppm): delta 4.48 (3H, s), 3.47 (2H, s), 2.96 (1H, s), 1.47-1.41 (2H, q), 1.02-0.99 (3H, d); LCMS (ESI), m/z, 90 [M+H]+; measured [alpha]D20.2+11.65° (C=1.22 g/100 mL in EtOH), lit. [alpha]D20+16.3° (c=4.5 in EtOH) (J. Org. Chem. 1996, 61, 2293-2304.).
92% With palladium on activated charcoal; hydrogen; In methanol; at 25℃; for 12h; Into a 1000-mL round-bottom flask was placed a solution of benzyl N-[(2S)-4-hydroxybutan-2-yl]carbamate (30 g, 134.4 mmol, 1.00 equiv) in methanol (500 mL) and palladium carbon (3 g, 0.10 equiv). The resulting solution was stirred at 25° C. for 12 h under an atmosphere of hydrogen. The solids were filtered out and the filtrate was concentrated under vacuum to afford 11.7 g (92percent) of (3S)-3-aminobutan-1-ol as an oil. 1H NMR (300 MHz, DMSO, ppm): delta 4.48 (3H, s), 3.47 (2H, s), 2.96 (1H, s), 1.47-1.41 (2H, q), 1.02-0.99 (3H, d); LCMS (ESI), m/z, 90 [M+H]+; measured [alpha]D20.2+11.65° (C=1.22 g/100 mL in EtOH), lit. [alpha]D20+16.3° (c=4.5 in EtOH) (J. Org. Chem. 1996, 61, 2293 2304.).
92% With palladium on activated charcoal; hydrogen; In methanol; at 25℃; for 12h; Step 3: (3R)-3-Aminobutan-l-ol and (3y)-3-Aminobutan-l-ol Into a 1000-mL round-bottom flask was placed a solution of benzyl N-[(2S)-4- hydroxybutan-2-yl]carbamate (30 g, 134.4 mmol, 1.00 equiv) in methanol (500 mL) and palladium carbon (3 g, 0.10 equiv). The resulting solution was stirred at 25°C for 12 h under an atmosphere of hydrogen. The solids were filtered out and the filtrate was concentrated under vacuum to afford 11.7 g (92percent) of (35)-3-aminobutan-l-ol as an oil. *H NMR (300MHz, DMSO, ppm): delta 4.48 (3H, s), 3.47 (2H, s), 2.96 (1H, s), 1.47-1.41 (2H, q), 1.02-0.99 (3H, d); LCMS (ESI), m/z, 90 [M+H] +; measured [a]D20 2 +11.65° (C=1.22g/100mL in EtOH), lit. [a]D20 +16.3° (c=4.5 in EtOH) (J. Org. Chem. 1996, 61 , 2293- 2304.). Using the above procedure, 12.0 g 12 g (94percent) of (3R)-3-aminobutan-l-ol was isolated as an oil. lU NMR (300MHz, DMSO, ppm): delta 4.48 (3H, s), 3.47 (2H, s), 2.96 (1H, s), 1.47-1.41 (2H, q), 1.02-0.99 (3H, d); LCMS (ESI), m/z, 90 [M+H] +; measured [a]D20 2 -11.1° (C = 0.32g/100mL in EtOH), lit. [a]D25 -25° (c= 1.25 in EtOH) (Tetrahedron: Asymmetry 1999, 10, 2213-2224).
92% With palladium on activated charcoal; hydrogen; In methanol; at 25℃; for 12h; Into a 1000-mL round-bottom flask was placed a solution of benzyl N-[(2S)-4-hydroxybutan-2-yllcarbamate (30 g, 134.4 mmol, 1.00 equiv) in methanol (500 mL) andpalladium carbon (3 g, 0.10 equiv). The resulting solution was stirred at 25°C for 12 h under an atmosphere of hydrogen. The solids were filtered out and the filtrate was concentrated under vacuum to afford 11.7 g (92percent) of (3S)-3-aminobutan-1-ol as an oil. ?H NMR (300MHz, DMSO, ppm): oe 4.48 (3H, s), 3.47 (2H, s), 2.96 (1H, s), 1.47-1.41 (2H, q), 1.02-0.99 (3H, d); LCMS(ESI), mlz, 90 [M+Hj measured [cL1D202 +11.65° (C=1.22gIlOOmL in EtOH), lit. [ctlD2° +16.3° (c=4.5 in EtOH) (J. Org. Chem. 1996, 61, 2293?2304.).
92% With palladium on activated charcoal; hydrogen; In methanol; at 25℃; for 12h; Into a 1000-mL round-bottom flask was placed a solution of benzyl A^-[(25')-4-hydroxybutan-2- yl]carbamate (30 g, 134.4 mmol, 1.00 equiv) in methanol (500 mL) and palladium carbon (3 g, 0.10 equiv). The resulting solution was stirred at 25°C for 12 h under an atmosphere of hydrogen. The solids were filtered out and the filtrate was concentrated under vacuum to afford 11.7 g (92percent) of (3S)-3- aminobutan-l-ol as an oil. NMR (300MHz, DMSO, ppm): delta 4.48 (3H, s), 3.47 (2H, s), 2.96 (1H, s), 1.47-1.41 (2H, q), 1.02-0.99 (3H, d); LCMS (ESI), m/z, 90 [M+H] +; measured [a]D20 2 +11.65° (C=1.22g/100mL in EtOH), lit. [a]D20 +16.3° (c=4.5 in EtOH) (J. Org. Chem. 1996, 61 , 2293-2304.).
92% With palladium 10% on activated carbon; hydrogen; In methanol; at 25℃; for 12h; Into a 1000-mL round-bottom flask was placed a solution of benzyl N-[(2S)-4-hydroxybutan-2-yl]carbamate (30 g, 134.4 mmol, 1.00 equiv) in methanol (500 mL) and palladium carbon (3 g, 0.10 equiv). The resulting solution was stirred at 25°C for 12 h under an atmosphere of hydrogen. The solids were filtered out and the filtrate was concentrated under vacuum to afford 11.7 g (92percent) of (3S)-3-aminobutan-1-ol as an oil. 1H NMR (300MHz, DMSO, ppm): delta 4.48 (3H, s), 3.47 (2H, s), 2.96 (1H, s), 1.47-1.41 (2H, q), 1.02-0.99 (3H, d); LCMS (ESI), mlz, 90 [M+H] measured [alpha]D20.2° +11.65° (C=1.22g/l00mL in EtOH), lit. [alpha]D20° +16.3° (c=4.5 in EtOH) (J. Org. Chem. 1996, 6], 2293?2304.).

YieldReaction ConditionsOperation in experiment
With hydrogenchloride; In methanol; at 25℃; General procedure: To a solution of (R)-tert-butyl(4-hydroxybutan-2-yl) carbamate (1.3 g, 6.87 mmol) in methanol (30 mL) was added HC1 (30 mL, 4M in MeOH), stirred at 25°C overnight, concentrated to afford the title compound (0.5 g).
  • 10
  • [ 61477-39-2 ]
  • [ 1939-99-7 ]
  • (3S,6R)-3-methyl-6-phenyl-1,2-thiazinane 1,1-dioxide [ No CAS ]
  • C11H15NO2S [ No CAS ]
  • 11
  • [ 61477-39-2 ]
  • [ 4352-30-1 ]
  • C18H35NO5S2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In tetrahydrofuran; at 0 - 20℃; for 16h; To a solution of <strong>[61477-39-2](3S)-3-aminobutan-1-ol</strong> (200 mg, 2.24 mmol) and triethylamine (0.79 mL, 5.61 mmol) in tetrahydrofuran (7 mL) at 0 °C was slowly added cyclohexylmethanesulfonyl chloride (1.0 g, 5.16 mmol) and the reaction was stirred at room temperature for 16 hours. Methyl tert-butyl ether (20 mL) was then added to precipitate triethylamine hydrochloride and the salt was removed by filtration. The filtrate was then concentrated to give crude bis-sulfonylated intermediate.
  • 12
  • [ 61477-39-2 ]
  • [ 124-63-0 ]
  • C6H15NO5S2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In tetrahydrofuran; at 0 - 20℃; for 16h; To a solution of (3S)-3-aminobutan-l-ol (3.0 g, 34 mmol) and triethylamine (12 mL, 84 mmol) in tetrahydrofuran (100 mL) at 0 °C was slowly added methanesulfonyl chloride (6.6 mL, 84 mmol). The reaction was then allowed to worm to room temperature and was stirred at that temperature for 16 hours. Methyl tert-butyl ether (100 mL) was then added to precipitate triethylamine hydrochloride and the salt was removed by filtration. The filtrate was then concentrated to give crude bis-sulfonylated intermediate.
  • 13
  • [ 61477-39-2 ]
  • [ 1939-99-7 ]
  • [ 1537863-65-2 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In tetrahydrofuran; at 0 - 20℃; for 16h; Prep -N-(4-Chlorobutan-2-yl)- 1 -phenylmethanesulfonamide Step 1 : (R)-3-(Phenylmethylsulfonamido)butyl phenylmethanesulfonate To a solution of (3R)-3-aminobutan-l-ol (1.0 g, 11.2 mmol) and triethylamine (3.3 mL, 23.6 mmol) in tetrahydrofuran (37 mL) at 0 °C was slowly added phenylmethanesulfonyl chloride (4.49 g, 23.6 mmol) and the reaction was stirred at room temperature for 16 hours. MTBE (100 mL) was then added and the Et3N- HC1 salt was removed by filtration. The filtrate was then concentrated to give crude (R)-3-(phenylmethylsulfonamido)butyl phenylmethanesulfonate which was used without purification. LCMS (ESI), m/z, 398 [M+H] +.
  • 14
  • [ 61477-39-2 ]
  • C15H17NO7 [ No CAS ]
  • C17H20N2O6 [ No CAS ]
YieldReaction ConditionsOperation in experiment
To compound 52 (460 mg, 1.42 mmol) in acetonitrile (20 mL) were added acetic acid (1.0 mL, 17.47 mmol), potassium carbonate (0.8 g, 5.7 mmol) <strong>[61477-39-2](S)-3-aminobutan-1-ol</strong> (0.39 mL, 4.27 mmol). After stirring at 70° C. for 24 h, it was concentrated and the residue was used for the next reaction. The solution of the above residue in THF (20 mL), MeOH (2 mL), and 1 N NaOH (5 mL) was stirred at room temperature for 1 h. The resulting mixture was acidified with 3 N HCl and concentrated to dryness. The residue was purified by column chromatography on silica gel using dichloromethane-20percent methanol in dichloromethane as eluents to get compound 78. LCMS-ESI+ (m/z): [M+H]+ calculated for C17H21N2O6: 349.14. found: 349.15.
  • 15
  • [ 61477-39-2 ]
  • [ 4352-30-1 ]
  • C18H35NO5S2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In tetrahydrofuran; at 20℃; for 16h; To a solution of <strong>[61477-39-2](3S)-3-aminobutan-1-ol</strong> (200 mg, 2.24 mmol) and triethylamine (0.79 mL, 5.61 mmol) in tetrahydrofuran (7 mL) at 0° C. was slowly added cyclohexylmethanesulfonyl chloride (1.0 g, 5.16 mmol) and the reaction was stirred at room temperature for 16 hours. Methyl tert-butyl ether (20 mL) was then added to precipitate triethylamine hydrochloride and the salt was removed by filtration. The filtrate was then concentrated to give crude bis-sulfonylated intermediate
  • 16
  • [ 61477-39-2 ]
  • [ 124-63-0 ]
  • N-[(1S)-3-chloro-1-methyl-propyl]methanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In tetrahydrofuran; at 0 - 20℃; for 16h; To a solution of <strong>[61477-39-2](3S)-3-aminobutan-1-ol</strong> (3.0 g, 34 mmol) and triethylamine (12 mL, 84 mmol) in tetrahydrofuran (100 mL) at 0° C. was slowly added methanesulfonyl chloride (6.6 mL, 84 mmol). The reaction was then allowed to worm to room temperature and was stirred at that temperature for 16 hours. Methyl tert-butyl ether (100 mL) was then added to precipitate triethylamine hydrochloride and the salt was removed by filtration. The filtrate was then concentrated to give crude bis-sulfonylated intermediate.
  • 17
  • 3(S)-benzamido-1-butanol [ No CAS ]
  • [ 61477-39-2 ]
YieldReaction ConditionsOperation in experiment
85% With hydrogenchloride; for 5h; Example operating procedures and the same post-processing method implemented by 60g 3 (S) - benzamido-1-butanol, 600mL of concentrated hydrochloric benzoyl hydrolytic reaction to give 3(S)-amino-1-butanol(IV) as colorless viscous liquid, 23.5 g, yield 85percent, ee value 99.3percent, content 99.2percent (GC method), Example 11 Preparation of 3(R)-amino-1-butanol (IV) Take 60g 3 (R) - benzamido-1-butanol, dissolved in 600mL of concentrated hydrochloric acid, into the thick-walled pressure-resistant glass reactor, at 110 deg.] C (external temperature) sealed reactor 5 hours, allowed to stand overnight at room temperature, the precipitated white solid was removed by filtration benzoic acid (37.2g dry weight, recovery rate 99percent, mp.121-122 , 99.5percent can be used benzamide starting material). The aqueous layer was evaporated under reduced pressure, the residue was washed three times with methylene chloride (150mL x 3) with, (washings were combined recoverable by distillation apply). Then, the mixture was carefully added with 55 mL of 50percent sodium hydrogencarbonate aqueous solution under cooling in an ice-water bath, evaporated to dryness under reduced pressure, and 150 mL of absolute ethanol was added thereto. The mixture was stirred well, then filtered and washed with 50 mL of absolute ethanol.The combined filtrate and washings, the first pressure steam to ethanol (ethanol can be applied the next batch) and then vacuum distillation collecting 59-60 / 10mmHg distillate, 3(R)-amino-1-butanol (IV), colorless viscous liquid, 23g, yield 83percent, ee value 99.4percent, content 99.2percent (GC method),
  • 18
  • [ 139243-55-3 ]
  • [ 61477-39-2 ]
YieldReaction ConditionsOperation in experiment
78% (S) -amino-butyric acid methyl ester hydrochloride, 300 mL of methanol and 42 g of potassium borohydride were subjected to a reduction reaction in the same manner as in Example 11 to give 3 (S) -amino-1- Butanol (IV) as a colorless viscous liquid, 27.1 g,Rate of 78percent, ee value of 99.2percent, content of 99.1percent (GC method) 60 g of ethyl 3 (R) -aminobutyrate hydrochloride 63 mL of a 50percent aqueous solution of sodium hydrogencarbonate was carefully added with cooling with ice-water bath. After stirring for 15 minutes, the mixture was extracted three times with dichloromethane (100 mL x 3) , Dried over anhydrous sodium sulfate, filtered and concentrated to dryness (recovered methylene chloride can be applied in the same procedure as described in the next reaction). After adding 300 mL of ethanol to the residue,40 g of potassium borohydride was added in portions at room temperature with stirring, and the reaction was continued at room temperature with stirring,TLC follow the test, about 12 hours of complete reaction, vacuum distillation of ethanol recovery (the next batch reaction in this step the same procedure applied), to the residue by adding 200mL of water, stirring at room temperature with 2N hydrochloric acid carefully adjust PH value to 3- 4, washed three times with dichloromethane (100mL x 3), (combined washing liquid, by distillation of dichloromethane recovery, in the next batch of this step in the same application)The aqueous phase was then adjusted to pH 9 with 2N aqueous sodium carbonate solution, evaporated to dryness under reduced pressure,150 mL of absolute ethanol was added,After thorough stirring, filtration,And then washed with 50mL absolute ethanol filter cake,The organic phases were combined,The ethanol was recovered by distillation at atmospheric pressure (the ethanol fraction was recovered by combining the pre-distillate from the vacuum distillation product,In the next batch of reaction to the same procedure used in this step),Then vacuum distillation,The 59-60 ° C / 10 mm Hg fraction was collected,To give 3 (R) -amino-1-butanol (IV),Colorless viscous liquid, 24.5 g, yield 77percent, ee value 99.2percent, content 99.1percent (GC method)
  • 19
  • [ 3775-72-2 ]
  • [ 61477-39-2 ]
YieldReaction ConditionsOperation in experiment
47% With sodium tetrahydroborate; zinc(II) chloride; In tetrahydrofuran; at 20 - 60℃; for 3.5h; Add 2 mL of anhydrous tetrahydrofuran and 43 g of anhydrous zinc chloride to the 2L autoclave (with little heat dissipation). Carefully add 24 g of sodium borohydride (note the exotherm and gas production). Stirred at room temperature for 30 minutes and then warmed to 50-60 ° C for 3 hours. After cooling to room temperature, 49 g of the above white solid was added portionwise and the temperature was controlled at 10 to 40 ° C. After the addition was complete, the temperature was slowly raised to reflux for 24 hours. The system became a gray suspension system, cooled to 10-15 ° C, slowly added 25 ml of methanol and 8 g of a 40percent aqueous solution of sodium hydroxide, and the temperature was controlled at 10 to 40 ° C. After adding, stir at room temperature for 3-5 hours. Filtered, washed with THF and filtered to give a colorless liquid. After concentration and distillation under reduced pressure (10 to 65 ° C), 17 g of a clear viscous liquid R-3-aminobutanol was obtained in 47percent yield. Purity 99.1percent, ee99.2percent.
  • 20
  • [ 61477-39-2 ]
  • [ 501-53-1 ]
  • [ 168827-91-6 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; In water; The purity was measured directly by gas chromatography. Ee assay: 3-aminobutanol was first reacted with benzyloxycarbonyl chloride in aqueous sodium hydroxide to form N-Cbc-3-aminobutanol and then detected by liquid phase. Column AD-H; Flowable n-hexane: isopropanol (9: 1); flow rate, 1 ml / min. Detection wavelength, 210 nm. Retention time, S-isomer, 11.1 min, R-isomer 12.2 min.
  • 21
  • [ 24424-99-5 ]
  • [ 61477-39-2 ]
  • [ 106539-36-0 ]
YieldReaction ConditionsOperation in experiment
55% With triethylamine; In dichloromethane; at 20℃; for 2h; [00614] To a solution of Example 127a (10 g, 0.11 mol) and TEA (17 g, 0.17 mol) in DCM (100 mL) was added Boc20 (29.4 g, 0.13 mol), which was stirred for 2 h at room temperature. The reaction mixture was concentrated under reduced pressure and which was purified by silica gel chromatography (Petroleum ether/EtOAc =1/1) to give the desired product Example 127b (11.5 g, yield 55percent) as a white solid.
In methanol; at 18 - 25℃; Di-tert-butyl dicarbonate (2.60 mL, 11.22 mmol) was added to a solution of (S)-3- aminobutan-l-ol (1.00 g, 11.2 mmol) in MeOH (10 mL) at room temperature. The mixture was stirred at room temperature and allowed to stand. The mixture was partitioned between water and DCM. The aqueous phase was extracted with DCM. The combined organic phases were dried (MgS04) and concentrated in vacuo. The residue was dissolved in DCM (10 mL), dried (MgS04) and concentrated in vacuo to afford the title compound.H NMR (400 MHz, CD3CN) 5 ppm 1.11 (d, J= 6.69 Hz, 3 H), 1.41 (s, 9 H), 1.44 - 1.51 (m, 1 H), 1.55 - 1.69 (m, 1 H), 2.85 - 3.05 (m, 1 H), 3.43 - 3.58 (m, 2 H), 3.61 - 3.80 (m, 1 H), 5.13 - 5.34 (m, 1 H)
With triethylamine; In dichloromethane; at 20℃; for 16h; To a solution of (S)-3-Aminobutan-1-ol (2.00 g, 22.4 mmol) in DCM (10.0 mL) was added TEA (4.74 mL, 33.7 mmol) and di-tert-butyl dicarbonate (5.67 mL, 24.7 mmol). The resulting mixture was stirred at RT for 16 hours. Upon completion, ice water was added, then the aqueous layer was extrated twice with DCM. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to give the title compound (4.12 g, crude).
  • 22
  • (S)-3-amino-1-butanol L-malate [ No CAS ]
  • [ 61477-39-2 ]
YieldReaction ConditionsOperation in experiment
90.3% With potassium ethoxide; In methanol; at 20℃; 27.7g of potassium ethoxide (0.33mol) was added in batches to 200ml of anhydrous methanol, and the temperature was controlled at 10-20°C.After 10 minutes, the system was dissolved, and 36 g of (S)-amino-1-butanol D-malate (0.16 mol) was added and stirred at room temperature for 0.5 to 1 minute.At the time, it is concentrated under reduced pressure (0.1MPa, 30-35°C) to remove most of the methanol, and 40ml of isopropyl acetate is added to continue the concentration and bring out.Residual methanol in the system. Add 200 ml of isopropyl acetate, stir at room temperature for 1 hour, remove the salt with suction, and reduce the amount of isopropyl acetate.Concentrate by pressure (0.1MPa, 40-50°C) to obtain a pale yellow liquid, warm up to 60°C to 90°C to 100°C and distill off at a temperature of 60°C.°C, 12.98 g of a colorless liquid is obtained, namely (S)-3-amino-1-butanol, purity >99percent, chiral purity >99.92percent, yield90.3percent.
  • 23
  • [ 61477-39-2 ]
  • C18H17NO5 [ No CAS ]
  • C21H22N2O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With acetic acid; at 80℃; for 3h; (0351) To a solution of Int-2j (1.00 g, 3.06 mmol) in tetrahydrofuran (40 mL) was added acetic acid (0.4 mL) and <strong>[61477-39-2](S)-3-aminobutan-1-ol</strong> (2.72 g, 30.6 mmol). The mixture was stirred at 80° C. for 3 h, cooled to room temperature and purified directly by preparative RP-HPLC to provide Int-10a. 1H NMR (400 MHz, CDCl3) delta 7.57-7.68 (m, 2H), 7.27-7.36 (m, 3H), 6.38-6.47 (m, 1H), 5.30 (d, J=2.8 Hz, 1H), 5.07 (d, J=2.8 Hz, 1H), 4.81-4.98 (m, 1H), 4.27-4.41 (m, 1H), 3.77-4.18 (m, 3H), 2.90-3.11 (m, 2H), 2.35-2.62 (m, 1H), 2.13-2.30 (m, 1H), 1.93-2.10 (m, 2H), 1.19-1.25 (m, 3H); Mass Calc'd for C21H22N2O4: 366.2, found 367.2 (M+H)+.
  • 24
  • [ 21240-34-6 ]
  • [ 61477-39-2 ]
  • 3-[(1S)-3-hydroxy-1-methylpropyl]-4,5-diphenyloxazol-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
59% A mixture of (S)-3-Aminobutan-1-ol (4.25 mL, 42.0 mmol) and 4,5-diphenyl-1,3- dioxol-2-one (10.0 g, 42.0 mmol) in DMF (125 mL) was allowed to stir at RT overnight. The reaction was diluted with H2O and extracted with EtOAc (X5), and the combined organic layers washed (H2O X5, brine), dried (Na2SO4) and concentrated in vacuo. The residue was treated with TFA (39.0 mL, 504 mmol) and the solution was allowed to stir for 2 hours. The solution was concentrated and the residue taken up in MeOH and treated with K2CO3(11.9 mL, 210 mmol) and the mixture was allowed to stir for 1 hour. The mixture was concentrated and the residue was diluted with H2O and extracted with EtOAc (X3), and the combined organic layers washed (H2O X2, brine), dried (Na2SO4) and concentrated in vacuo. The residue was purified by column chromatography (0 to 100percent EtOAc in hexanes) to give a colorless solid (7.60 g, 59percent).
  • 25
  • [ 61477-39-2 ]
  • 4-chloro-1-methyl-6-nitroquinolin-2(1H)-one [ No CAS ]
  • 4-[[(1S)-3-hydroxy-1-methylpropyl]amino]-1-methyl-6-nitroquinolin-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
56% With N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; at 160℃; for 20h;Sealed tube; Inert atmosphere; An oven-dried microwave vial (10-20 ml_ volume) was charged with 4-chloro-1- methyl-6-nitroquinolin-2(1 /-/)-one (Intermediate F1 ; 800 mg, 3.4 mmol) and (S)-3- aminobutan-1-ol (446 mg, 5.0 mmol). The reaction vial was flushed with Ar, sealed with a cap and then further flushed with Ar. Anhydrous NMP (10 ml_) was added followed by DIPEA (1.2 ml_, 6.9 mmol). The reaction mixture was heated at 160C in a heating block for 20 h. The reaction mixture was allowed to cool to rt. The reaction mixture was diluted with water (100 ml_), and the aqueous mixture was extracted with EtOAc (100 ml_). The organic extract was washed with water (2 x 25 ml_). The aqueous washings were combined and further extracted with EtOAc (3 x 50 ml_). The organic extracts were combined, dried (Na2S04) and concentrated in vacuo. The crude reaction mixture was dry-loaded onto silica and purified by flash chromatography (50 g KP-sil; 0% to 10% MeOH in CH2CI2) affording (S)-4-((4- hydroxybutan-2-yl)amino)-1-methyl-6-nitroquinolin-2(1 /-/)-one (547 mg, 56%) as a yellow solid. 1 H NMR (500 MHz, DMSO-cfe) 6 9.1 1 (d, J = 2.5 Hz, 1 H), 8.37 (dd, J = 9.4, 2.5 Hz, 1 H), 7.60 (d, J = 9.4 Hz, 1 H), 7.1 1 (d, J = 7.9 Hz, 1 H), 5.59 (s, 1 H), 4.57 (t, J = 5.0 Hz, 1 H), 3.80-3.71 (m, 1 H), 3.55 (s, 3 H), 3.53-3.48 (m, 2 H), 1.94-1.87 (m, 1 H), 1.67-1.60 (m, 1 H), 1.23 (d, J = 6.4 Hz, 3 H).
 

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