5-Methylisoxazole-3-carbonyl chloride → HCID 178488219, 화합물

HRID 432409

반응식

HRID 432409 반응식
[CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7](Cl)=[O:8])[CH:3]=1.[NH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[N:23][C:24]=3[NH2:26])[N:19]([C@H:27]3[CH2:32][CH2:31][C@@H:30]([N:33]4[CH2:38][CH2:37][N:36]([CH3:39])[CH2:35][CH2:34]4)[CH2:29][CH2:28]3)[N:18]=2)=[CH:13][C:12]=1[O:40][CH3:41]>N1C=CC=CC=1>[NH2:26][C:24]1[N:23]=[CH:22][N:21]=[C:20]2[N:19]([C@H:27]3[CH2:32][CH2:31][C@@H:30]([N:33]4[CH2:34][CH2:35][N:36]([CH3:39])[CH2:37][CH2:38]4)[CH2:29][CH2:28]3)[N:18]=[C:17]([C:14]3[CH:15]=[CH:16][C:11]([NH:10][C:7]([C:4]4[CH:3]=[C:2]([CH3:1])[O:6][N:5]=4)=[O:8])=[C:12]([O:40][CH3:41])[CH:13]=3)[C:25]=12

참가 물질

4

반응물 2

HCID 27368945-Methylisoxazole-3-carbonyl chlorideHCID 178488197HCID 178488197, 화합물

생성물 1

HCID 178488219HCID 178488219, 화합물수율 38.3%

시약·촉매·용매 1

HCID 1049Pyridine용매

실험 절차

5-Methyl-3-isoxazolecarbonyl chloride (20 mg, 0.137 mmol) was added to a solution of cis-3-(4-amino-3-methoxyphenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (30 mg, 0.067 mmol) in pyridine (0.5 mL). After 5 hours, the solvent was evaporated and the residue was purified by preparative HPLC (Hypersil BSD C18, 5 um, 100×21 mm, 0%-100% acetonitrile/0.05M ammonium acetate over 10 min, 25.0 mL/min). The resulting products were further purified by partitioning between dichloromethane (4 ml) and 1.0 N sodium hydroxide (2 ml) and passing through an Empore™ high performance extraction disk cartridge (C 18-SD octadecyl) to give cis-N3-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-5-methyl-3-isoxazolecarboxamide (14 mg, 38%). 1H NMR (DMSO-d6) δ 1.81 (m, 2H), 2.14 (m, 2H), 2.35 (m, 2H), 2.53 (s, 3H), 2.76 (m, 3H), 3.37 (bm, 8H), 3.99 (s, 3H), 4.93 (m, 1H), 6.74 (s, 1H), 7.36 (m, 2H), 8.26 (m, 1H), 9.48 (s, 1H); LCMS (Finigan-Column: Pecosphere, C18, 3 um, 33×4.6 mm. Eluents: 0% B/A to 100% B/A in 4 min. (B: acetonitrile, A: 50 mM ammonia acetate buffer, pH 4.5), 3.0 mL/min.): MH+ =546.4, Rt=1.82 min.

후처리

  1. customthe solvent was evaporated
  2. customthe residue was purified by preparative HPLC (Hypersil BSD C18, 5 um, 100×21 mm, 0%-100% acetonitrile/0.05M ammonium acetate over 10 min, 25.0 mL/min)
  3. customThe resulting products were further purified
  4. customby partitioning between dichloromethane (4 ml) and 1.0 N sodium hydroxide (2 ml)
  5. extractionpassing through an Empore™ high performance extraction disk cartridge (C 18-SD octadecyl)

출처 및 근거

ORD 기록
ord-3876ff4dd08c44ec978a7bec1a894e69
출처 데이터셋
uspto-grants-2003_12
특허 번호
US06660744B1

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