2-Aminothiazole → 2,2-dimethyl-3-phenyl-3-(3-phenyl-1H-indazol-6-yl)-N-(thiazol-2-yl)propanamide

HRID 563395노트

반응식

HRID 563395 반응식
[CH3:1][C:2]([CH3:28])([CH:6]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:7]1[CH:15]=[C:14]2[C:10]([C:11]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[N:12][NH:13]2)=[CH:9][CH:8]=1)[C:3]([OH:5])=O.[NH2:29][C:30]1[S:31][CH:32]=[CH:33][N:34]=1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH3:1][C:2]([CH3:28])([CH:6]([C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[C:7]1[CH:15]=[C:14]2[C:10]([C:11]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[N:12][NH:13]2)=[CH:9][CH:8]=1)[C:3]([NH:29][C:30]1[S:31][CH:32]=[CH:33][N:34]=1)=[O:5]

참가 물질

6

반응물 4

HCID 21552-AminothiazoleHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 670056622,2-dimethyl-3-phenyl-3-(3-phenyl-1H-indazol-6-yl)propanoic acid

생성물 1

HCID 592527712,2-dimethyl-3-phenyl-3-(3-phenyl-1H-indazol-6-yl)-N-(thiazol-2-yl)propanamide수율 28.6%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
80 °C

실험 절차

To a stirred solution of 2,2-dimethyl-3-phenyl-3-(3-phenyl-1H-indazol-6-yl)propanoic acid (26 mg, 0.07 mmol), 2-aminothiazole (28 mg, 0.28 mmol), and diisopropylethylamine (0.05 mL) in anhydrous DMF (0.2 mL) was added HATU (106 mg, 0.28 mmol) under argon. After stirring at rt for 2.5 hr and 80° C. for 1 hr, the mixture was concentrated. Purification using reverse phase HPLC (YMC S5 20×100 mm, 10 min. run, solvent A: 10% MeOH: 90% H2O: 0.1% TFA, solvent B: 90% MeOH, 10% H2O, 0.1% TFA) gave 2,2-dimethyl-3-phenyl-3-(3-phenyl-1H-indazol-6-yl)-N-(thiazol-2-yl)propanamide (Example 112, 9 mg, 0.02 mmol, 28% yield) as a solid. MS found: (M+H)+=453. 1H-NMR (500 MHz, CDCl3) δ ppm 7.96 (1H, d, J=8.25 Hz) 7.86 (2H, d, J=8.25 Hz) 7.50 (1H, d, J=8.25 Hz) 7.46 (2H, d, J=8.25 Hz) 7.39-7.43 (2H, m) 7.35 (2H, d, J=7.70 Hz) 7.17-7.26 (4 H, m), 6.96 (1H, d, J=3.30 Hz) 4.62 (1H, s) 1.45 (6H, d, J=3.85 Hz).

후처리

  1. concentrationthe mixture was concentrated
  2. customPurification
  3. customphase HPLC (YMC S5 20×100 mm, 10 min. run, solvent A: 10% MeOH: 90% H2O: 0.1% TFA, solvent B: 90% MeOH, 10% H2O, 0.1% TFA)

출처 및 근거

ORD 기록
ord-f159853ab02b41e2b8f7a9eface7f24b
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08067447B2

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