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 1800768노트

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HRID 1800768 반응식
[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]

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 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

생성물 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)benzamide수율 77%

시약·촉매·용매 1

HCID 1049Pyridine용매

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온도
90 °C

실험 절차

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.

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=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

출처 및 근거

ORD 기록
ord-bd51151110cb4567a9e7d3c8460b2654
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08344135B2

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