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

HRID 1800761노트

반응식

HRID 1800761 반응식
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:22])=[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:23]([C:25]([CH3:37])([O:27][C:28]1[CH:29]=[C:30]([CH:34]=[CH:35][CH:36]=1)[C:31](O)=[O:32])[CH3:26])#[N:24].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[CH:7]=[C:2]([NH:1][C:31](=[O:32])[C:30]4[CH:34]=[CH:35][CH:36]=[C:28]([O:27][C:25]([C:23]#[N:24])([CH3:26])[CH3:37])[CH:29]=4)[CH:3]=[CH:4][C:5]=3[CH3:22])[N:10]=[CH:11][C:12]=2[N:17]=1)(=[O:21])[CH3:20]

참가 물질

6

반응물 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 668104733-(1-Cyano-1-methylethoxy)benzoic acidHCID 86646095N-{5-[(5-amino-2-methylphenyl)amino][1,3]thiazolo[5,4-d]pyrimidin-2-yl}acetamide

생성물 1

HCID 59507068N-(3-{[2-(acetylamino)[1,3]thiazolo[5,4-d]pyrimidin-5-yl]amino}-4-methylphenyl)-3-(1-cyano-1-methylethoxy)benzamide수율 46%

시약·촉매·용매 1

HCID 1049Pyridine용매

실험 절차

A solution of N-{5-[(5-amino-2-methylphenyl)amino][1,3]thiazolo[5,4-d]pyrimidin-2-yl}acetamide (83 mg, 265 μmol) produced in Example D35(v), 3-(1-cyano-1-methylethoxy)benzoic acid (71 mg, 345 μmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (120 mg, 318 μmol) in pyridine (3 mL) was stirred at room temperature for 1.5 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=30/70→0/100), and the fractions containing the object product were concentrated under reduced pressure. The obtained residue was recrystallized from tetrahydrofuran and hexane to give the title compound (61 mg, 46%) as a colorless solid.

후처리

  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=30/70→0/100)
  7. additionthe fractions containing the object product
  8. concentrationwere concentrated under reduced pressure
  9. customThe obtained residue was recrystallized from tetrahydrofuran and hexane

출처 및 근거

ORD 기록
ord-2df40c3a6e1544909a76b20ffbafd256
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08344135B2

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