Phosphate → N2-{5-[5-(1-methyl-1H-pyrazol-4-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridin-3-yl}-N-(2,2,2-trifluoroethyl)valinamide

HRID 510212노트

반응식

HRID 510212 반응식
Cl[C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[CH:12]=[C:13]([NH:17][C@H:18]([C:22]([NH:24][CH2:25][C:26]([F:29])([F:28])[F:27])=[O:23])[CH:19]([CH3:21])[CH3:20])[CH:14]=[N:15][CH:16]=3)=[CH:9][N:8]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:5]2=[N:6][CH:7]=1.[CH3:38][N:39]1[CH:43]=[C:42](B2OC(C)(C)C(C)(C)O2)[CH:41]=[N:40]1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.P([O-])([O-])([O-])=O>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH3:38][N:39]1[CH:43]=[C:42]([C:2]2[CH:3]=[C:4]3[C:10]([C:11]4[CH:12]=[C:13]([NH:17][C@H:18]([C:22]([NH:24][CH2:25][C:26]([F:27])([F:28])[F:29])=[O:23])[CH:19]([CH3:21])[CH3:20])[CH:14]=[N:15][CH:16]=4)=[CH:9][N:8]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:5]3=[N:6][CH:7]=2)[CH:41]=[N:40]1

참가 물질

8

반응물 4

HCID 1061PhosphateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 131733258N2-[5-(5-chloro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]-N-(2,2,2-trifluoroethyl)valinamide

생성물 1

HCID 131733262N2-{5-[5-(1-methyl-1H-pyrazol-4-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridin-3-yl}-N-(2,2,2-trifluoroethyl)valinamide

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 6228Dimethylformamide용매

반응 조건

온도
100 °C

실험 절차

To a solution of N2-[5-(5-chloro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]-N-(2,2,2-trifluoroethyl)valinamide 2-1a (200 mg, 0.360 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (CA) (90 mg, 0.432 mmol), X-PHOS (30.9 mg, 0.065 mmol), palladium(II) acetate (9.69 mg, 0.043 mmol) in DMF (2 mL) was added phosphate tribasic (153 mg, 0.719 mmol) and water (0.4 mL). The mixture was evacuated then N2 purged 3 times and heated at 100° C. for overnight. After cooling the reaction was filtered and filtrate was loaded directly onto HPLC Reverse phase (C-18), eluting with acetonitrile/water (0.1% TFA), to give product 8-1a as a colorless foam. MS APCI: [M+H]+ m/z=602.1.

후처리

  1. customThe mixture was evacuated
  2. customN2 purged 3 times
  3. temperatureAfter cooling the reaction
  4. filtrationwas filtered
  5. washeluting with acetonitrile/water (0.1% TFA)

출처 및 근거

ORD 기록
ord-6fecbb097ea84b67a7244eeb37fa0194
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09096598B2

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