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Chemical Structure| 1445-39-2 Chemical Structure| 1445-39-2

Structure of 1445-39-2

Chemical Structure| 1445-39-2

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Product Details of [ 1445-39-2 ]

CAS No. :1445-39-2
Formula : C4H4IN3
M.W : 221.00
SMILES Code : IC1=CN=C(N)N=C1
MDL No. :MFCD01075666
InChI Key :HAFKCGZQRIIADX-UHFFFAOYSA-N
Pubchem ID :241102

Safety of [ 1445-39-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 1445-39-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 39.15
TPSA ?

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

51.8 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.24
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

0.51
Log Po/w (WLOGP)?

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

0.67
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.

0.33
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

1.31
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.81

Water Solubility

Log S (ESOL):?

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

-2.09
Solubility 1.81 mg/ml ; 0.00819 mol/l
Class?

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

Soluble
Log S (Ali)?

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

-1.17
Solubility 15.0 mg/ml ; 0.0679 mol/l
Class?

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

Very 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

-2.25
Solubility 1.24 mg/ml ; 0.00561 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.

-7.29 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

1.0 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)

1.91

Application In Synthesis of [ 1445-39-2 ]

* 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 [ 1445-39-2 ]

[ 1445-39-2 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 109-12-6 ]
  • [ 1445-39-2 ]
YieldReaction ConditionsOperation in experiment
22.2% With sulfuric acid; iodine; acetic acid; periodic acid; In water; at 80℃; for 24h;Inert atmosphere; Mixture of 2-aminopyrimidine (2.4 g, 25 mmol, 1.0 eq.) and elemental iodine (2.7 g, 10.7 mmol, 0.43eq.) was added to 60 ml of glacial acetic acid, and then added periodic acid (0.86 g, 3.76 mmol, 0.15 eq.) and 0.5 ml concentrated sulfuric acid dissolved in sulfuric acid solution 3 ml of water. Place reactions in a nitrogen atmosphere , the reaction was heated to 80 C for 24 hours. The reaction was then poured into a saturated aqueous solution of sodium thiosulfate in until a clear solution, (200 ml × 3) and extracted with dichloromethane, the combined organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure, after column chromatography silica gel to give a white solid 2-amino-5-iodopyrimidine (1.4 g, yield 22.2%).
0.4 g With iodine; In dimethyl sulfoxide; at 120℃; for 1h; To a solution of pyrimidin-2-amine (1.0 g, 0.010 mol) in DMSO (10 mL) was added iodine (3.2 g, 0.012 mol). The reaction mixture was stirred at 120C for 1 h. The reaction mass was quenched in water and excess of iodine was neutralised with sodium metabisulphate. The reaction mass was extracted with ethyl acetate and concentrated to afford 0.400 g of the desired product.
  • 2
  • [ 1445-39-2 ]
  • [ 98-09-9 ]
  • [ 90841-92-2 ]
  • 3
  • [ 1445-39-2 ]
  • [ 153400-52-3 ]
  • exo-2-(2-aminopyrimidin-5-yl)-7-carbomethoxy-7-azabicyclo<2.2.1>heptane [ No CAS ]
  • 4
  • [ 109-12-6 ]
  • [ 1600-27-7 ]
  • [ 7732-18-5 ]
  • [ 1445-39-2 ]
  • 5
  • [ 1445-39-2 ]
  • copper (II)-thiophenolate [ No CAS ]
  • 5-phenylsulfanyl-pyrimidin-2-ylamine [ No CAS ]
  • 6
  • [ 1445-39-2 ]
  • potassium-<4-nitro-thiophenolate> [ No CAS ]
  • [ 874494-43-6 ]
  • 7
  • [ 1445-39-2 ]
  • [ 130277-32-6 ]
  • [ 307303-59-9 ]
  • 8
  • [ 1445-39-2 ]
  • 2-fluoro-5-iodopyrimidine [ No CAS ]
  • 9
  • [ 1445-39-2 ]
  • [ 103-63-9 ]
  • 5-phenethyl-pyrimidin-2-ylamine [ No CAS ]
  • 10
  • [ 142-08-5 ]
  • [ 1445-39-2 ]
  • 1-(2-amino-pyrimidin-5-yl)-1<i>H</i>-pyridin-2-one [ No CAS ]
  • 11
  • [ 1445-39-2 ]
  • [ 1066-54-2 ]
  • [ 857265-74-8 ]
YieldReaction ConditionsOperation in experiment
Example 3Synthesis of 5-ethynylpyrimidin-2-amine A flask was charged with <strong>[1445-39-2]5-iodopyrimidin-2-amine</strong> (25.0 g, 110 mmol), acetonitrile (900 ml, 110 mmol), trimethylsilylacetylene (35 ml, 241 mmol), triethylami?e (93 ml, 658 mmol), Pd(PPh3)4CI2 (3.9 g, 5.5 mmol) and finally copper(l) iodide (1.1 g, 5.5 mmol). The flask was put under vacuum then filled with argon and stirred at RT overnight using a mechanical stirrer. The solvent was removed under vacuum, the residue taken up in methanol (600ml) and potassium carbonate (152 g, 1097 mmol) was added. The mixture was stirred at RT using mechanical stirring for 2 hrs. Activated carbon (~50ml_) was added to the reaction and stirring continued for 15min. The reaction mixture was then filtered through a plug of celite and the filtrate was concentrated to a volume of ~400mL and the precipitate was filtered. The filtrate was concentrated down to a thick paste which was slurried in ~150mL of 10%MeOH/H2O for 20 min at RT. The solids were then filtered off to afford 5-ethynylpyrimidin-2-amine.
  • 12
  • [ 1445-39-2 ]
  • [ 108-24-7 ]
  • [ 849236-67-5 ]
YieldReaction ConditionsOperation in experiment
23% With pyridine; at 110℃; for 48h; Step 1: N- (5-LODOPYRIMIDIN-2-YL) acetamide (248) [0400] 5-lodo-pyrimidin-2-ylamine (17,1. 1 g, 4.98 MMOL) and acetic anhydride (14.94 MMOL, 1.41 mL) were dissolved in pyridine (20 mL) and stirred at 110C for 48 hours. The reaction mixture was cooled and quenched with water (50 mL). Ethyl acetate (100 mL) was added and the resulting white precipitate was collected by filtration to afford title compound 248 as a white solid (300 mg, 23% yield NMR: (DMSO) 8 10.67 (s, 1H), 8.85 (s, 2H), 2.18 (s, 3H).
  • 13
  • [ 1445-39-2 ]
  • [ 1066-54-2 ]
  • [ 857265-75-9 ]
YieldReaction ConditionsOperation in experiment
100% With N-ethyl-N,N-diisopropylamine;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; copper(l) iodide; In ethyl acetate; at -20 - 20℃; for 6h; Intermediate 5; o 5-[(Trimethylsilyl)ethynyl]pyrimidin-2-aminePdCl2dppf (146 mg) was added to a solution of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> (221 mg), trimethylsilylacetylene (491 mg), CuI (57 mg) and DIPEA (259 mg) in EtOAc (5 mL) at -20C under an inert atmosphere. The reaction was allowed to warm to ambient s temperature and stirred for 6 hours. The reaction mixture was diluted with water (10 mL). The organic layer was separated, dried (MgSO4), filtered and concentrated. The crude product was used directly without further purification (191 mg, 100%); 1H NMR (CDCl3) 0.26 (s, 9H), 5.19 (bs, 2H)3 8.39 (s, 2H); MS m/e M^+MeCN 233. o
100% With N-ethyl-N,N-diisopropylamine;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; copper(l) iodide; In ethyl acetate; at -20 - 20℃; for 6h; 5-[(Trimethylsilyl)ethynyl]pyrimidin-2-amine PdCl2dppf (146 mg) was added to a solution of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> (221 mg), trimethylsilylacetylene (491 mg), CuI (57 mg) and DIPEA (259 mg) in EtOAc (5 mL) at -20 C. under an inert atmosphere. The reaction was allowed to warm to ambient temperature and stirred for 6 hours. The reaction mixture was diluted with water (10 mL). The organic layer was separated, dried (MgSO4), filtered and concentrated. The crude product was used directly without further purification (191 mg, 100%); 1H NMR (CDCl3) 0.26 (s, 9H), 5.19 (bs, 2H), 8.39 (s, 2H);
100% With N-ethyl-N,N-diisopropylamine;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; copper(l) iodide; In ethyl acetate; at -20 - 20℃; for 6h; PdCl2dppf (146 mg) was added to a solution of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> (221 mg), trimethylsilylacetylene (491 mg), Cul (57 mg) and DIPEA (259 mg) in EtOAc (5 mL) at - 20C under an inert atmosphere. The reaction was allowed to warm to ambient temperature and stirred for 6 hours. The reaction mixture was diluted with water (10 mL). The organic layer was separated, dried (MgS04), filtered and concentrated. The crude product was used directly without further purification (191 mg, 100%) ; 'H NMR (CDCl3) ; 0.26 (s, 9H), 5.19 (bs, 2H), 8.39 (s, 2H); MS m/e MH++MeCN 233.
With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In acetonitrile; at 20℃; for 3h; Into a IL round bottom flask was placed the 2-amino-5- iodopyrimidine (8.0 g, 36.2 mmol) , acetonitrile (30OmL), triethylamine (3OmL), TMS acetylene (7.68g, 78.2 mmol), palladium dichloro-bis-triphenylphosphine (1.26g, 1.8 mmol), and copper(I) iodide (0.342g, 1.8 mmol) . The vessel was filled with argon gas and allowed to stir at room temperature for 3 hours. The solvent was evaporated and the crude was taken up in methanol (40OmL) . Then excess potassium carbonate (10eq) was added, and the mixture was stirred at room temperature for 1.5 hours. Activated charcoal was added and the mixture was filtered through celite. The filtrate was concentrated under reduced pressure to afford a tan solid, which was added to a solution of 10% methanol in water (20OmL) . The resulting precipitate was isolated by filtration, dried in a vacuum oven to constant mass and afforded the title compound as a tan solid. MS m/z = 120 [M+H]+. CaIc'd for C6H5N3: 119.

  • 14
  • [ 1445-39-2 ]
  • [ 857266-55-8 ]
  • [ 857266-56-9 ]
YieldReaction ConditionsOperation in experiment
86% With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In DMF (N,N-dimethyl-formamide); at 60℃; for 4h; Triethylamine (1.0 mL) was added to a degassed solution of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> (275 mg), tert-butyl 3-ethynylphenyl (methyl) carbamate (Intermediate 42) (298 mg) PdCl2 (PPh3) 2 (17 mg) and cuprous iodide (1.25 mg) in DMF (5.0 mL). The mixture was heated to 60C for 4 hours and concentrated in vacuo. Purification by flash chromatography on silica using 0- 10% MeOH in DCM as eluent gave the title compound as a yellow solid (344 mg, 86%). lH NMR (CDCl3) 1.47 (s, 9H), 3.27 (s, 1H), 5.22 (s, br, 2H), 7.23-7. 31 (m, 3H), 7. 39 (s, 1H), 8.45 (s, 2H); MS m/e MH+ 325.
  • 15
  • [ 1445-39-2 ]
  • [ 14235-81-5 ]
  • 5-[(4-aminophenyl)ethynyl]pyrimidin-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
63% With N,N,N',N'-tetramethylguanidine;copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); In DMF (N,N-dimethyl-formamide); at 60℃; for 2.5h; A mixture of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> (1.10 g), 4-ethynylaniline (0.82 g), 1,1, 3,3- tetramethylguanidine (0.81 g), and copper (I) iodide (9.5 mg) in dry DMF (3.0 mL) was stirred and degassed with nitrogen. Tetrakis (triphenylphosphine) palladium (0) (115 mg) was added and the mixture heated at 60 C for 2.5 hours. The solvent was evaporated and the residue was triturated with DCM. The solid formed was filtered off and washed with water then dissolved in 1: 1 DCM/MeOH, filtered then evaporated. The solid obtained was triturated with ether and dried to give the title compound (0.67 g, 63%) ; 'HNMR (DMSO-d6) 5.50 (s, 2H), 6.55 (d, 2H), 6.95 (s, 2H), 7.15 (d, 2H), 8.35 (s, 2H) ; MS m/e MH+ 211.
  • 16
  • [ 1445-39-2 ]
  • [ 149507-26-6 ]
  • [ 890021-33-7 ]
YieldReaction ConditionsOperation in experiment
Example 38; 5-(4-(6,7-Dimethoxyquinolin-4-yloxy)-3-fluorophenyl)-N- phenylpyrimidin-2-amine; Step 1: Preparation of 5- (3-fluoro-4-methoxgammaphengammal) pyrimidin-2- amine; In a 500 mL round bottom flask under N2, 3-fluoro-4- methoxyphenylboronic acid (5.0 g, 29.4 mmol) and 5-iodopyrimidin- 2-amine (5.5 g, 24.9 mmol) were mixed. Toluene (100 mL) , EtOH (40 mL) and H2O (20 mL) were added, followed by the addition of Na2CO3 (3.0 g, 24.2 mmol). A stream of N2 was bubbled through the mixture for 5 min before the catalyst Pd(PPh)4 (0.30 g, 0.26 mmol) was added. The mixture was heated at 80 C under N2 for 20 h whereby it was cooled to RT. A solution of NaOH (5 N, 10 mL) was added to the mixture and stirring was continued for 10 min. The mixture was filtered and the solid was washed with H2O (3 x 10 mL) , followed by a mixture of hexanes - EtOAc (1:1, 30 mL) . The solid was dried in the air to give the title compound. MS (ESI pos. ion) m/z: 220. CaIc'd for C11H10FN3O: 219.08.
  • 17
  • [ 1445-39-2 ]
  • [ 32779-38-7 ]
YieldReaction ConditionsOperation in experiment
31% With tert.-butylnitrite; copper dichloride; In acetonitrile; at 20 - 60℃;Inert atmosphere; Step A. Preparation of 2-chloro-5-iodopyrimidine [00166] To a stirring solution of <strong>[1445-39-2]5-iodopyrimidin-2-amine</strong> (2.21 g, 10.0 mmol) in CH3CN (20 ml) at room temperature under argon was added copper (II) chloride (2.02 g, 15 mmol) and tert-butyi nitrite (1.55 g, 15 mmol). The reaction mixture was placed in a preheated oil bath (60 0C) under Argon. The reaction mixture was cooled to room temperature and 20 ml of ether was added. The resulting insoluble material was filtered and the filtrate was concentrated. The crude product was dissolved in a small amount of DCM (~2 ml) and loaded onto an 80 g ISCO silica gel column which was eluted with a 20 min gradient from 0% to 100% EtOAc/Hexanes. 778 mg (31%) of 2-chloro-5-iodopyrimidine was obtained as an off- white solid. 1H NMR (400 MHz, CDCl3) delta ppm 8.79 (s, 2 H).
28% With sodium hydroxide; sodium nitrate; In hydrogenchloride; water; (d) A suspension of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> (40 g) in concentrated hydrochloric acid (150 ml) was treated dropwise at a temperature of 25 to 30 C. with a solution of sodium nitrate (40 g) in water (70 ml). The reaction mixture was stirred at a temperature of 25 to 30 C. for a further 2 hr and then neutralised by the addition of aqueous 20% sodium hydroxide, the temperature of the reaction mixture being maintained at 10 to 20 C. during the neutralisation by external cooling. The neutralised reaction mixture was filtered to remove solids and the solids were washed several times with chloroform. The filtrate was extracted with chloroform and the combined chloroform washings and extracts were dried and the chloroform was removed by distillation under reduced pressure to give crude 2-chloro-5-iodopyrimidine as a pale brown solid (12 g, 28%) with m.p. 125 C. (Reference m.p. 129-130 C. J. Chem. Soc. (C), 1971, 1889).
1.7 g With tert.-butylnitrite; copper dichloride; In acetonitrile; at 70℃; To a solution of <strong>[1445-39-2]5-iodopyrimidin-2-amine</strong> (10.0 g, 0.045 mol) in acetonitrile (150 mL) was added CuCl2 (11.57 g, 0.067 mol) and teri-butyl nitrite (6.99 g, 0.067 mol). The reaction mass was heated at 70C for 5-6 h. The reaction mass was diluted with ether and the solid obtained was filtered off. The obtained product was purified with column chromatography on silica gel eluting with DCM to afford 1.700 g of the desired product
  • 18
  • [ 1445-39-2 ]
  • (4-chloro-3-nitrophenyl)boronic acid [ No CAS ]
  • [ 742700-78-3 ]
YieldReaction ConditionsOperation in experiment
70% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 150℃; for 0.166667h;Microwave heating; A mixture of 4-chloro-3-nitrophenylboronic acid (600 mg, 3.0 mmoles), <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> (680 mg, 3.0 mmoles), sodium carbonate (900 mg, 8.5 mmoles) and tetrakis(triphenylphosphine)palladium(0) (80 mg, 0.07 mmoles) in 3:1 dimethylformamide-water (10 ml_) was sealed in a pressure tube and heated at 1500C for 10 minutes in a microwave reactor. The mixture was diluted with water and extracted with ethyl acetate (x2). Combined extracts were washed with brine, dried and evaporated. Flash chromatography (0-5% methanol-dichloromethane) gave the title compound (525 mg, 70%). 1 H NMR(400 MHz, DMSO-alphafe) delta ppm 7.04 (s, 2 H) 7.81 (d, J=8.59 Hz, 1 H) 8.00 (dd, J=8.59, 2.27 Hz, 1 H) 8.36 (d, J=2.27 Hz, 1 H) 8.70 (s, 2 H).
  • 19
  • [ 1445-39-2 ]
  • [ 816-40-0 ]
  • 2-ethyl-6-iodo-imidazo[1,2-a]pyrimidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
In ethanol;Heating / reflux; 755 mg of 1-bromo-2-butanone was dissolved in 15 ml of ethanol, 1.0 g of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> was added and the mixture was stirred all night by heating under reflux. After cooling down to room temperature, the solvents were distilled outunder reflux, ethyl acetate followed by saturated sodium bicarbonate aqueous solution were added. Organic layer was dried with anhydrous sodium sulfate, and the solvents were distilled outunder reduced pressure. The obtained residues were purified by silicagel column chromatography (ethyl acetate) to obtain 110 mg of the above compound as a white solid. 1HNMR(300MHz,CDCl3.)delta:1.38(3H,t,J=7.0Hz), 2.88(2H,q,J=7.0Hz), 7.25(1H,s), 8.52(1H,d,J=2.4Hz), 8.58(1H,d,J=2.4Hz) ESI-MS Found:m/z 274.0[M+H]+
  • 20
  • [ 1445-39-2 ]
  • [ 54060-30-9 ]
  • [ 857264-92-7 ]
YieldReaction ConditionsOperation in experiment
60% With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In N,N-dimethyl-formamide; at 95℃; for 2h; 5-[(3-aminophenyl)ethynyl]pyrimidin-2-amine <strong>[1445-39-2]2-Amino-5-iodopyrimidine</strong> (2.21 g), bis(triphenylphosphine)palladium dichloride (350 mg) and copper(I) iodide (40 mg) were stirred in DMF (100 mL)-triethylamine (20 mL) and degassed with nitrogen for 10 min. 3-Ethynyl aniline (1.29 g) was added and the mixture heated to 95 C. for 2 hours. The solvent was evaporated and the residue was purified by trituration with DCM (20 mL) to give the title compound as a brown solid (1.25 g, 60%); 1H NMR (DMSO-d6) 5.21 (bs, 2H), 6.58-6.70 (m, 3H), 7.03-7.07 (m, 3H), 8.40 (s, 2H); MS m/e MH+211.
60% <strong>[1445-39-2]2-Amino-5-iodopyrimidine</strong> (2.21 g), bis (triphenylphosphine) palladium dichloride (350 mg) and copper (I) iodide (40 mg) were stirred in DMF (100 mL)- triethylamine (20 mL) and degassed with nitrogen for 10 min. 3-Ethynyl aniline (1.29 g) was added and the mixture heated to 95 C for 2 hours. The solvent was evaporated and the residue was purified by trituration with DCM (20 mL) to give the title compound as a brown solid (1.25 g, 60%); 'H NMR (DMSO-d6) 5.21 (bs, 2H), 6.58-6. 70 (m, 3H), 7.03-7. 07 (m, 3H), 8.40 (s, 2H); MS m/e MH+ 211.
  • 21
  • [ 1445-39-2 ]
  • [ 2491-38-5 ]
  • [ 956499-77-7 ]
YieldReaction ConditionsOperation in experiment
646 mg (corresponding to 3.0 mmol) of 2-bromo-4'-hydroxyacetophenone and 668 mg (corresponding to 3.0 mmol) of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> were dissolved in 20 mL of acetonitrile. The resulting solution was refluxed in an oil bath at 110C for 8 hours. After the completion of the reaction, the reaction solution was cooled down to room temperature, and precipitates were filtered and recovered. The precipitates were washed with acetonitrile and dried under reduced pressure. The resulting crude crystals were suspended in a mixed solution of 10 mL of water and 10 mL of methanol. Then, about 15 mL of a saturated sodium hydrogencarbonate solution was added thereto, and the mixture was sonicated for 3 minutes using an ultrasonic washing machine. Precipitates were filtered and recovered from the resulting mixture, sufficiently washed with water, and dried under reduced pressure, to obtain 737 mg (corresponding to 2.19 mmol) of 2-(4'-hydroxyphenyl)-6-iodoimidazo[1,2-a]pyrimidine (Fig. 1-8, Step 2).
646 mg (corresponding to 3.0 mmol) of 2-bromo-4'-hydroxyacetophenone and 668 mg (corresponding to 3.0 mmol) of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> were dissolved in 20 mL of acetonitrile. The resulting solution was refluxed in an oil bath at 110C for 8 hours. After the completion of the reaction, the reaction solution was cooled down to room temperature, and precipitates were filtered and recovered. The precipitates were washed with acetonitrile and dried under reduced pressure. The resulting crude crystals were suspended in a mixed solution of 10 mL of water and 10 mL of methanol. Then, about 15 mL of a saturated sodium hydrogencarbonate solution was added thereto, and the mixture was sonicated for 3 minutes using an ultrasonic washing machine. Precipitates were filtered and recovered from the resulting mixture, sufficiently washed with water, and dried under reduced pressure, to obtain 737 mg (corresponding to 2.19 mmol) of 2-(4'-hydroxyphenyl)-6-iodoimidazo[1,2-a]pyrimidine (Fig. 4, Step 2). The NMR measurement results of the resulting 2-(4'-hydroxyphanyl)-6-iodoimidazo[1,2-a]pyrimidine (internal standard: dimethylformamide) are shown below. NMR apparatus employed: JNM-ECP-500 (manufactured by Japan Electron Optics Laboratory Co., Ltd. (JEOL)) 1H-NMR (solvent: dimethylformamide-d7, resonance frequency: 500 MHz): delta 9.80 (br. s, 1H), 9.35 (d, J = 2.3 Hz, 1H), 8.60 (d, J = 2.3 Hz, 1H), 8.23 (s, 1H), 7.94-7.90 (m, 2H), 6.98-6.94 (m, 2H). 13C-NMR (solvent: dimethylformamide-d7, resonance frequency: 125 MHz): delta 158.87, 154.00, 147.18, 146.77, 139.07, 127.68, 124.50, 115.85, 106.10, 73.46.
With sodium hydrogencarbonate; In methanol; water; acetonitrile; , Step 1). 646 mg (corresponding to 3.0 mmol) of 2-bromo-4'-hydroxyacetophenone and 668 mg (corresponding to 3.0 mmol) of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> were dissolved in 20 mL of acetonitrile. The resulting solution was refluxed in an oil bath at 110C for 8 hours. After the completion of the reaction, the reaction solution was cooled down to room temperature, and precipitates were filtered and recovered. The precipitates were washed with acetonitrile and dried under reduced pressure. The resulting crude crystals were suspended in a mixed solution of 10 mL of water and 10 mL of methanol. Then, about 15 mL of a saturated sodium hydrogencarbonate solution was added thereto, and the mixture was sonicated for 3 minutes using an ultrasonic washing machine. Precipitates were filtered and recovered from the resulting mixture, sufficiently washed with water, and dried under reduced pressure, to obtain 737 mg (corresponding to 2.19 mmol) of 2-(4'-hydroxyphenyl)-6-iodoimidazo[1,2-a]pyrimidine (
With sodium hydrogencarbonate; In methanol; water; acetonitrile; , Step 1). 646 mg (corresponding to 3.0 mmol) of 2-bromo-4'-hydroxyacetophenone and 668 mg (corresponding to 3.0 mmol) of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> were dissolved in 20 mL of acetonitrile. The resulting solution was refluxed in an oil bath at 110C for 8 hours. After the completion of the reaction, the reaction solution was cooled down to room temperature, and precipitates were filtered and recovered. The precipitates were washed with acetonitrile and dried under reduced pressure. The resulting crude crystals were suspended in a mixed solution of 10 mL of water and 10 mL of methanol. Then, about 15 mL of a saturated sodium hydrogencarbonate solution was added thereto, and the mixture was sonicated for 3 minutes using an ultrasonic washing machine. Precipitates were filtered and recovered from the resulting mixture, sufficiently washed with water, and dried under reduced pressure, to obtain 737 mg (corresponding to 2.19 mmol) of 2-(4'-hydroxyphenyl)-6-iodoimidazo[1,2-a]pyrimidine (

  • 22
  • [ 1445-39-2 ]
  • [ 905856-70-4 ]
  • 23
  • [ 1445-39-2 ]
  • [ 110-13-4 ]
  • [ 1139875-13-0 ]
  • 25
  • [ 1445-39-2 ]
  • [ 1147938-59-7 ]
  • [ 1147938-92-8 ]
YieldReaction ConditionsOperation in experiment
32% With potassium phosphate;copper(l) iodide; cis-[2-(dimethylamino)cyclohexyl]amine; In N,N-dimethyl-formamide; at 100℃; for 24h; Example 21 N-(3-(7-(4-((DIMETHYLAMINO)METHYL)PHENYL)-7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)PHENYL)-3-(TRIFLUOROMETHYL)BENZAMIDE (COMPOUND NO. 111) A mixture of N-(3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl)-3-(trifluoromethyl)-benzamide (0.12 g, 0.31 mmol), <strong>[1445-39-2]5-iodopyrimidin-2-amine</strong> (67 mg, 0.0.31 mmol), copper (I) iodide (24 mg, 0.13 mmol), potassium phosphate (140 mg, 0.66 mmol), and N,N-dimethylcyclohexane-1,2-diamine (31 mg, 0.22 mmol) in DMF (0.5 mL) were stirred for 24 hours at 100 C. The reaction mixture was filtered and purified by reverse phase chromatography to give N-(3-(7-(4-((dimethylamino)methyl)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl)-3-(trifluoromethyl)benzamide (63 mg, 32% yield). MS: m/z 516.4 [M+H].
  • 27
  • [ 1445-39-2 ]
  • [ 929278-54-6 ]
  • 5-[5-(2-aminopyrimidin-5-yl)-1H-benzimidazol-1-yl]-3-({(1R)-1-[2-(trifluoromethyl)phenyl]ethyl}oxy)thiophene-2-carboxamide [ No CAS ]
  • 28
  • [ 1445-39-2 ]
  • [ 1181621-18-0 ]
  • [ 1181621-08-8 ]
YieldReaction ConditionsOperation in experiment
57% With copper(l) iodide; triethylamine;tetrakis(triphenylphosphine) palladium(0); In acetonitrile; at 82℃; for 3h;Inert atmosphere; A mixture of alkyne 7 (710 mg, 2.224 mmol), iodopyrimidine 4 (676 mg, 3.06 mmol), palladiumtetrakistriphenylphosphine (290 mg, 0.251 mmol) and copper (I) iodide (103 mg, 0.541 mmol) was suspended in degassed mixture of acetonitrile (15 mL) and triethylamine (5 mL, 35.9 mmol). The thick mixture was then stirred under argon at 82C for 3h; cooled down to room temperature and diluted with DCM, washed with saturated NH4C1, dried over MgSO4, filtered and concentrated. The purification was performed by flash column chromatography on silica gel (eluent EtOAc) to afford compound 8 (526 mg, 57% yield). IH NMR (400 MHz, DMSO-d6) delta (ppm): 8.97 (s, IH), 8.46-8.41 (m, 2H), 8.19 (s, IH), 7.79 (s, IH), 7.50 (d, J = 8.0 <n="92"/>Hz, IH), 7.41 (t, J = 7.8 Hz, IH), 7.26 (t, J = 8.0 Hz, IH), 7.14 (s, 2H), 7.08-7.02 (m, 3H). MS (m/z): 413.1 (M+H).
  • 29
  • [ 1445-39-2 ]
  • [ 1181621-20-4 ]
  • [ 1181621-11-3 ]
YieldReaction ConditionsOperation in experiment
57% With copper(l) iodide; triethylamine;bis-triphenylphosphine-palladium(II) chloride; In acetonitrile; at 40℃; for 3h; To a suspension of compound 13 (600 mg, 1.879 mmol) in acetonitrile (4.70 niL) was added Et3N (1.572 mL, 11.28 mmol) and <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> (4, 415 mg, 1.879 mmol). Then copper (I) iodide (17.89 mg, 0.094 mmol), and bis(triphenylphosphine)palladium(II) chloride (33.0 mg, 0.047 mmol), were successively added degassing the reaction mixture between and after each addition of catalysts. The mixture was stirred at 40C over 3h., diluted with DCM and quenched with sat NH4C1 and cone. NH4OH. The resulting emulsion was allowed to sit for 2h, the aqueous layer was then removed to render an organic paste which was partitioned between EtOAc and IM HCl. The layers were separated and the organic layer was concentrated to a volume of 20 mL. The resulting solid was filtered through a Buchner funnel and rinsed with EtOAc to afford title compound 14 (441 mg, 57% yield). IH NMR (400 MHz, DMSO-d6) delta (ppm): 9.29 (bs, IH), 8.48 (s, IH), 8.46 (s, 2H), 8.05 (s, IH), 7.82 (bs, IH), 7.45 (t, J = 8.0 Hz, IH), 7.26 (d, J = 8.0 Hz, IH), 7.22 (t, J = 7.6 Hz, IH), 6.89 (d, J = 7.4 Hz, IH), 6.85 (s, IH), 6.81 (d, J = 8.4 Hz, IH). MS (m/z): 413.3 (M+H).
  • 30
  • [ 1445-39-2 ]
  • [ 1181621-17-9 ]
  • [ 1181621-07-7 ]
YieldReaction ConditionsOperation in experiment
17% With copper(l) iodide; triethylamine;bis-triphenylphosphine-palladium(II) chloride; In acetonitrile; at 81℃; for 3h;Inert atmosphere; A mixture of compound 3 (530 mg, 1.968 mmol), iodide 4 (221 mg, 1.000 mmol), CuI (92 mg, 0.48 mmol) and PdC12(dppf) (139 mg, 0.19 mmol) was dissolved in a mixture acetonitrile (12 mL) and TEA (4 mL, 28.7 mmol), degassed under vacuum and stirred under argon at 81C for 3h. The reaction mixture was diluted with DCM, washed with sat. NH4C1, sat NaHCO3 and water, then dried (MgSO4), filtered and concentrated. The residue was purified by flash column chromatography (eluent EtOAc) to afford compound 5 (16 mg, 17% yield). IH NMR (400 MHz, DMSO-d6) delta (ppm): 8.92 (s, IH), 8.41 (s, 2H), 8.36 (s, IH), 8.03 (s, IH), 7.79 (s, IH), 7.50 (d, J = 8.4 Hz, IH), 7.26 (t, J = 8.0 Hz, IH), 7.22-7.17 (m, IH), 7.14 (s, 2H), 7.07 (dt, J = 6.4, 1.2 Hz, IH), 6.60 (dd, J = 8.4, 1.4 Hz, IH), 6.55-6.47 (m, IH). MS (m/z): 363.2 (M+H).
  • 32
  • [ 1445-39-2 ]
  • [ 942070-47-5 ]
  • [ 1309365-20-5 ]
  • 33
  • [ 1445-39-2 ]
  • [ 25015-63-8 ]
  • [ 402960-38-7 ]
  • 34
  • [ 1445-39-2 ]
  • [ 2923-28-6 ]
  • [Ag(2-amino-5-iodopyrimidine)2](trifluoromethanesulfonate) [ No CAS ]
  • [Ag(2-amino-5-iodopyrimidine)(trifluoromethanesulfonate)]n*H2O [ No CAS ]
  • 35
  • [ 1445-39-2 ]
  • [ 2923-28-6 ]
  • [Ag(2-amino-5-iodopyrimidine)]6(trifluoromethanesulfonate)6 [ No CAS ]
 

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Technical Information

Categories

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[ 1445-39-2 ]

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[ 1445-39-2 ]

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