3-(Trifluoromethoxy)benzoic acid → N-(3-{[2-(acetylamino)[1,3]thiazolo[5,4-d]pyrimidin-5-yl](cyclopropyl)amino}phenyl)-3-(trifluoromethoxy)benzamide

HRID 1800721Notes

Reaction equation

HRID 1800721 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([N:8]([CH:22]2[CH2:24][CH2:23]2)[C:9]2[N:10]=[CH:11][C:12]3[N:17]=[C:16]([NH:18][C:19](=[O:21])[CH3:20])[S:15][C:13]=3[N:14]=2)[CH:5]=[CH:6][CH:7]=1.[F:25][C:26]([F:38])([F:37])[O:27][C:28]1[CH:29]=[C:30]([CH:34]=[CH:35][CH:36]=1)[C:31](O)=[O:32].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(=O)([O-])O.[Na+]>N1C=CC=CC=1>[C:19]([NH:18][C:16]1[S:15][C:13]2[N:14]=[C:9]([N:8]([CH:22]3[CH2:24][CH2:23]3)[C:4]3[CH:3]=[C:2]([NH:1][C:31](=[O:32])[C:30]4[CH:34]=[CH:35][CH:36]=[C:28]([O:27][C:26]([F:25])([F:37])[F:38])[CH:29]=4)[CH:7]=[CH:6][CH:5]=3)[N:10]=[CH:11][C:12]=2[N:17]=1)(=[O:21])[CH3:20]

Participants

6

Reactant 4

HCID 660963-(Trifluoromethoxy)benzoic acidHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86646086N-{5-[(3-aminophenyl)(cyclopropyl)amino][1,3]thiazolo[5,4-d]pyrimidin-2-yl}acetamide

Product 1

HCID 59506939N-(3-{[2-(acetylamino)[1,3]thiazolo[5,4-d]pyrimidin-5-yl](cyclopropyl)amino}phenyl)-3-(trifluoromethoxy)benzamideYield 71.8%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A solution of N-{5-[(3-aminophenyl)(cyclopropyl)amino][1,3]thiazolo[5,4-d]pyrimidin-2-yl}acetamide (120 mg, 353 μmol) produced in Example D21(v), 3-(trifluoromethoxy)benzoic acid (77 mg, 371 μmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (161 mg, 424 μmol) in pyridine (3 mL) was stirred at room temperature for 30 min. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate solution (15 mL), and the mixture was extracted with ethyl acetate (20 mL, 5 mL). The combined organic layer was washed with saturated brine (5 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (ethyl acetate/methanol=100/0→98/2), and the fractions containing the object product were concentrated under reduced pressure. The obtained residue was recrystallized from ethyl acetate to give the title compound (134 mg, 71%) as colorless crystals.

Workup

  1. extractionthe mixture was extracted with ethyl acetate (20 mL, 5 mL)
  2. washThe combined organic layer was washed with saturated brine (5 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationThe insoluble material was filtered off
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe obtained residue was purified by basic silica gel column chromatography (ethyl acetate/methanol=100/0→98/2)
  7. additionthe fractions containing the object product
  8. concentrationwere concentrated under reduced pressure
  9. customThe obtained residue was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-8cf7f52270424ce7acd4fb46269eaac1
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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