Sodium Bicarbonate → N-(5-{[2-(acetylamino)[1,3]thiazolo[5,4-d]pyrimidin-5-yl]amino}-4-chloro-2-fluorophenyl)-3-(1-cyano-1-methylethyl)benzamide

HRID 1800767Notes

Reaction equation

HRID 1800767 reaction equation
[NH2:1][C:2]1[C:3]([F:23])=[CH:4][C:5]([Cl:22])=[C:6]([NH:8][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:7]=1.[C:24]([C:26]([C:29]1[CH:30]=[C:31]([CH:35]=[CH:36][CH:37]=1)[C:32](O)=[O:33])([CH3:28])[CH3:27])#[N:25].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]([NH:8][C:6]3[C:5]([Cl:22])=[CH:4][C:3]([F:23])=[C:2]([NH:1][C:32](=[O:33])[C:31]4[CH:35]=[CH:36][CH:37]=[C:29]([C:26]([C:24]#[N:25])([CH3:27])[CH3:28])[CH:30]=4)[CH:7]=3)[N:10]=[CH:11][C:12]=2[N:17]=1)(=[O:21])[CH3:20]

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 571495383-(2-Cyanopropan-2-yl)benzoic acidHCID 86646101N-{5-[(5-amino-2-chloro-4-fluorophenyl)amino][1,3]thiazolo[5,4-d]pyrimidin-2-yl}acetamide

Product 1

HCID 59506942N-(5-{[2-(acetylamino)[1,3]thiazolo[5,4-d]pyrimidin-5-yl]amino}-4-chloro-2-fluorophenyl)-3-(1-cyano-1-methylethyl)benzamideYield 67%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A solution of N-{5-[(5-amino-2-chloro-4-fluorophenyl)amino][1,3]thiazolo[5,4-d]pyrimidin-2-yl}acetamide (100 mg, 283 μmol), 3-(1-cyano-1-methylethyl)benzoic acid (128 mg, 680 μmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (258 mg, 680 μmol) in pyridine (3 mL) was stirred at 90° C. for 9 hr. 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 (hexane/ethyl acetate=10/90→0/100), 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 (99 mg, 67%) 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 (hexane/ethyl acetate=10/90→0/100)
  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-80ed6b76b8b24737a6175c2067c21966
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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