Methanol → HCID 59506968, compound

HRID 1800668Notes

Reaction equation

HRID 1800668 reaction equation
[NH2:1][C:2]1[S:3][C:4]2[N:5]=[C:6]([N:11]([CH3:31])[C:12]3[CH:13]=[C:14]([NH:18][C:19](=[O:30])[C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:29])([F:28])[F:27])[CH:21]=4)[CH:15]=[CH:16][CH:17]=3)[N:7]=[CH:8][C:9]=2[N:10]=1.[CH:32]1([C:35](Cl)=[O:36])CC1.CO.[OH-].[Na+]>N1C=CC=CC=1.CN(C)C1C=CN=CC=1>[C:35]([NH:1][C:2]1[S:3][C:4]2[N:5]=[C:6]([N:11]([CH3:31])[C:12]3[CH:13]=[C:14]([NH:18][C:19](=[O:30])[C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:28])([F:29])[F:27])[CH:21]=4)[CH:15]=[CH:16][CH:17]=3)[N:7]=[CH:8][C:9]=2[N:10]=1)(=[O:36])[CH3:32]

Participants

7

Reactant 4

HCID 887MethanolHCID 14798Sodium HydroxideHCID 77637Cyclopropanecarbonyl chlorideHCID 86646067HCID 86646067, compound

Product 1

HCID 59506968HCID 59506968, compoundYield 28,124.699%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Procedure

To a solution of N-{3-[(2-amino[1,3]thiazolo[5,4-d]pyrimidin-5-yl)(methyl)amino]phenyl}-3-(trifluoromethyl)benzamide (268 mg, 604 μmol) in pyridine (5 mL) were added N,N-dimethylpyridine-4-amine (23.9 mg, 196 μmol) and cyclopropanecarbonyl chloride (200 μL, 2.20 μmol), and the mixture was stirred at room temperature for 1 hr. To the reaction solution were added methanol (10 mL) and 2N aqueous sodium hydroxide solution (1 mL), and the mixture was stirred at room temperature for 1 more hr. The reaction solution was concentrated under reduced pressure, and diluted with ethyl acetate (100 mL) and tetrahydrofuran (10 mL). The diluted solution was washed with water (50 mL), 0.1N hydrochloric acid (50 mL) and saturated aqueous sodium hydrogen carbonate solution (50 mL), dried over anhydrous magnesium sulfate, and the insoluble material was filtered off. The filtrate was concentrated under reduced pressure, and the residue was purified by basic silica gel column chromatography (ethyl acetate/methanol=100/0→80/20), and recrystallized from ethyl acetate and tetrahydrofuran to give the title compound (compound of Example D2) (301 mg, 97%) as colorless crystals.

Workup

  1. stirringthe mixture was stirred at room temperature for 1 more hr
  2. concentrationThe reaction solution was concentrated under reduced pressure
  3. additiondiluted with ethyl acetate (100 mL) and tetrahydrofuran (10 mL)
  4. washThe diluted solution was washed with water (50 mL), 0.1N hydrochloric acid (50 mL) and saturated aqueous sodium hydrogen carbonate solution (50 mL)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationthe insoluble material was filtered off
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customthe residue was purified by basic silica gel column chromatography (ethyl acetate/methanol=100/0→80/20)
  9. customrecrystallized from ethyl acetate and tetrahydrofuran

Sources & evidence

ORD record
ord-48a88f3877614d6391fd85c8c55dcf79
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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