1-Methylimidazole → HCID 178485568, 화합물

HRID 2279917노트

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HRID 2279917 반응식
[Br:1][C:2]1[N:7]=[C:6]([C:8](=[O:11])[NH:9][CH3:10])[C:5]([NH:12][C:13]2[C:18]([C:19]([F:22])([F:21])[F:20])=[CH:17][N:16]=[C:15]([NH:23][C:24]3[CH:36]=[CH:35][C:27]([CH2:28][CH2:29][CH2:30][CH2:31][PH:32](=[O:34])[OH:33])=[CH:26][C:25]=3[O:37][CH3:38])[N:14]=2)=[CH:4][CH:3]=1.[CH3:39][C:40]([CH3:58])([CH2:43][N:44]1[CH:48]=[C:47]([B:49]2[O:53][C:52]([CH3:55])([CH3:54])[C:51]([CH3:57])([CH3:56])[O:50]2)[CH:46]=[N:45]1)[CH2:41]O.CN1C=CN=C1.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1>ClCCCl>[Br:1][C:2]1[N:7]=[C:6]([C:8](=[O:11])[NH:9][CH3:10])[C:5]([NH:12][C:13]2[C:18]([C:19]([F:22])([F:20])[F:21])=[CH:17][N:16]=[C:15]([NH:23][C:24]3[CH:36]=[CH:35][C:27]([CH2:28][CH2:29][CH2:30][CH2:31][PH:32](=[O:33])[O:34][CH2:39][C:40]([CH3:58])([CH3:41])[CH2:43][N:44]4[CH:48]=[C:47]([B:49]5[O:53][C:52]([CH3:55])([CH3:54])[C:51]([CH3:57])([CH3:56])[O:50]5)[CH:46]=[N:45]4)=[CH:26][C:25]=3[O:37][CH3:38])[N:14]=2)=[CH:4][CH:3]=1

참가 물질

6

반응물 4

HCID 13901-MethylimidazoleHCID 2724699PyBOPHCID 678124422,2-Dimethyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propan-1-ol2회HCID 178485566HCID 178485566, 화합물2회

생성물 1

HCID 178485568HCID 178485568, 화합물수율 45%

시약·촉매·용매 1

HCID 111,2-Dichloroethane용매

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온도
60 °C

실험 절차

A suspension of (4-{[4-{[6-bromo-2-(methylcarbamoyl)pyridin-3-yl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)propylphosphinic acid (Compound 74B, 0.500 g, 0.810 mmol) and 2,2-dimethyl-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]propan-1-ol (Compound 47B, 227 mg, 0.809 mmol) in 1,2-dichloroethane (24.4 mL) and 1-methylimidazole (0.967 mL, 12.1 mmol) was charged with (benzotriazol-1-yloxy)tripyrrolidino-phosphonium hexafluorophosphate (2530 mg, 4.85 mmol). After stirring at 60° C. for 16 hours, the reaction mixture was quenched with water (10 mL) and extracted with DCM (20 mL). The organic layer was washed with NaHCO3 (10 mL), washed with brine (15 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to a brown oil. The crude material was purified using a Teledyne ISCO Combiflash® Rf system using 1:1 DCM-EtOAc/MeOH (100:0→95:5) as eluent. The fractions containing product were combined and concentrated under reduced pressure to yield an off-white foam (318.1 mg, 45%). MS (ESI): m/z 879.93/881.94 [M+H]+. UPLC: tR=1.67 min (UPLC-TOF: polar—2 min).

후처리

  1. customthe reaction mixture was quenched with water (10 mL)
  2. extractionextracted with DCM (20 mL)
  3. washThe organic layer was washed with NaHCO3 (10 mL)
  4. washwashed with brine (15 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure to a brown oil
  8. customThe crude material was purified
  9. additionThe fractions containing product
  10. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-6b233bbab1154284b426ae441e3160bb
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09133224B2

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