1-Methylimidazole → N-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-yl)-1H-indazole-6-carboxamide

HRID 1410017노트

반응식

HRID 1410017 반응식
Cl.[NH2:2][CH:3]1[CH2:7][CH2:6][N:5]([C:8]2[N:9]=[C:10]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([O:26][CH3:27])[CH:19]=3)[C:11]3[N:16]=[CH:15][S:14][C:12]=3[N:13]=2)[CH2:4]1.[NH:28]1[C:36]2[C:31](=[CH:32][CH:33]=[C:34]([C:37](O)=[O:38])[CH:35]=2)[CH:30]=[N:29]1.CCN=C=NCCCN(C)C.CN1C=CN=C1>C(Cl)Cl>[CH3:27][O:26][C:20]1[CH:19]=[C:18]([NH:17][C:10]2[C:11]3[N:16]=[CH:15][S:14][C:12]=3[N:13]=[C:8]([N:5]3[CH2:6][CH2:7][CH:3]([NH:2][C:37]([C:34]4[CH:35]=[C:36]5[C:31]([CH:30]=[N:29][NH:28]5)=[CH:32][CH:33]=4)=[O:38])[CH2:4]3)[N:9]=2)[CH:23]=[CH:22][C:21]=1[O:24][CH3:25]

참가 물질

6

반응물 4

HCID 13901-MethylimidazoleHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 162279381H-indazole-6-carboxylic acidHCID 683792715-(3-aminopyrrolidin-1-yl)-N-(3,4-dimethoxyphenyl)thiazolo[5,4-d]pyrimidin-7-amine hydrochloride

생성물 1

HCID 66551738N-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-yl)-1H-indazole-6-carboxamide수율 36%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

A mixture of 5-(3-aminopyrrolidin-1-yl)-N-(3,4-dimethoxyphenyl)thiazolo[5,4-d]pyrimidin-7-amine hydrochloride (100 mg, 0.245 mmol), 1H-indazole-6-carboxylic acid (40 mg, 0.245 mmol), EDCI (97 mg, 0.49 mmol) and N-methylimidazole (60 mg, 0.735 mmol) in 10 mL of DCM was stirred at room temperature for 16 hours. The mixture was washed with water (5 mL), The organic layer was dried over Na2SO4. After filtration and concentration, the residue was purified by preparative HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 ml/inj, flow rate: 20 ml/min; wavelength: 214 nm and 254 nm; the gradient conditions are: 25% acetonitrile/75% water (0.1% TFA V/V) initially, and then proceed to 50% acetonitrile/50% water (0.1% TFA V/V) in a linear fashion after just 9 min.) to give N-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-yl)-1H-indazole-6-carboxamide (45 mg, 36%) as white solid. 1H NMR (300 MHz, DMSO): δ 9.69 (s, 1H), 8.84 (s, 1H), 8.74 (d, 1H, J=6.3 Hz), 8.14 (s, 1H), 8.06 (s, 1H), 7.89 (s, 1H), 7.81 (d, 1H, J=8.4 Hz), 7.63-7.44 (m, 2H), 6.92 (d, 1H, J=9.0 Hz), 4.62-4.25 (m, 2H), 3.96-3.66 (m, 10H), 2.35-2.11 (m, 3H). LC-MS: 516.9 [M+H]+, tR=1.38 min. HPLC: 100% at 214 nm, 100% at 254 nm, tR=5.76 min.

후처리

  1. washThe mixture was washed with water (5 mL)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationAfter filtration and concentration
  4. customthe residue was purified by preparative HPLC (Gemini 5u C18 150×21.2 mm
  5. wait25% acetonitrile/75% water (0.1% TFA V/V) initially, and then proceed to 50% acetonitrile/50% water (0.1% TFA V/V) in a linear fashion after just 9 min.

출처 및 근거

ORD 기록
ord-6e72f57fb3504a7bbc3a2136861450e4
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08921383B2

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