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

HRID 1800768Notes

Reaction equation

HRID 1800768 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.[CH3:24][C:25]([C:29]1[CH:30]=[C:31]([CH:35]=[CH:36][CH:37]=1)[C:32](O)=[O:33])([CH3:28])[C:26]#[CH:27].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:25]([CH3:24])([CH3:28])[C:26]#[CH:27])[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 862274143-(2-Methylbut-3-yn-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 59507001N-(5-{[2-(acetylamino)[1,3]thiazolo[5,4-d]pyrimidin-5-yl]amino}-4-chloro-2-fluorophenyl)-3-(1,1-dimethylprop-2-yn-1-yl)benzamideYield 77%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
90 °C

Procedure

A solution of N-{5-[(5-amino-2-chloro-4-fluorophenyl)amino][1,3]thiazolo[5,4-d]pyrimidin-2-yl}acetamide (78 mg, 221 μmol) produced in Example D46(iii), 3-(1,1-dimethylprop-2-yn-1-yl)benzoic acid (79 mg, 442 μmol) produced in Example D20(iii) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (168 mg, 442 μmol) in pyridine (3 mL) was stirred at 90° C. for 5 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=20/80→0/100), and the fractions containing the object product were concentrated under reduced pressure. The obtained residue was recrystallized from ethyl acetate and hexane to give the title compound (89 mg, 77%) 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=20/80→0/100)
  7. additionthe fractions containing the object product
  8. concentrationwere concentrated under reduced pressure
  9. customThe obtained residue was recrystallized from ethyl acetate and hexane

Sources & evidence

ORD record
ord-bd51151110cb4567a9e7d3c8460b2654
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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