Tributylstannane → 3-[4-(8-Aza-bicyclo[3.2.1]oct-8-ylmethyl)-phenyl]-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

HRID 1505945노트

반응식

HRID 1505945 반응식
[C:1]([C:3]1[N:11]=[CH:10][C:9]2[N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:7]3[N:20]=[CH:21][C:22]([C:24]4[CH:46]=[CH:45][C:27]([CH2:28][N:29]5[CH:34]6[CH2:35][CH2:36][CH:30]5[CH2:31][CH:32](OC(N5C=CN=C5)=S)[CH2:33]6)=[CH:26][CH:25]=4)=[CH:23][C:6]=3[C:5]=2[CH:4]=1)#[N:2].CC(N=NC(C#N)(C)C)(C#N)C.C([SnH](CCCC)CCCC)CCC>C1(C)C=CC=CC=1>[CH:34]12[N:29]([CH2:28][C:27]3[CH:45]=[CH:46][C:24]([C:22]4[CH:21]=[N:20][C:7]5[N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:17])([CH3:18])[CH3:19])[C:9]6[CH:10]=[N:11][C:3]([C:1]#[N:2])=[CH:4][C:5]=6[C:6]=5[CH:23]=4)=[CH:25][CH:26]=3)[CH:30]([CH2:36][CH2:35]1)[CH2:31][CH2:32][CH2:33]2

참가 물질

5

반응물 3

HCID 5948TributylstannaneHCID 6547AzobisisobutyronitrileHCID 58266558Imidazole-1-carbothioic acid O-(8-{4-[6-cyano-9-(2-trimethylsilanylethoxymethyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrol-3-yl]-benzyl}-8-aza-bicyclo[3.2.1]oct-3-yl)ester

생성물 1

HCID 582665503-[4-(8-Aza-bicyclo[3.2.1]oct-8-ylmethyl)-phenyl]-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile수율 84%

시약·촉매·용매 1

HCID 1140Toluene용매

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온도
110 °C

실험 절차

To a solution of imidazole-1-carbothioic acid O-(8-{4-[6-cyano-9-(2-trimethylsilanylethoxymethyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrol-3-yl]-benzyl}-8-aza-bicyclo[3.2.1]oct-3-yl) ester (182 mg, 0.28 mmol) and AIBN (60 mg, 0.36 mmol) in toluene (10 mL) under an argon atmosphere was added tributyltin hydride (0.58 mL, 1.85 mmol). On complete addition, the reaction was heated at 110° C. for 15 minutes then allowed to cool to ambient temperature. The mixture was concentrated in vacuo and the resultant residue was purified by flash chromatography (silica, 50 g column, Biotage, 0-5% MeOH in DCM) to afford the title compound as a white solid (123 mg, 84%). 1H NMR (CDCl3, 300 MHz): 9.26 (d, J=1.0 Hz, 1H), 9.03 (d, J=2.2 Hz, 1H), 8.69 (d, J=2.2 Hz, 1H), 8.51 (d, J=1.0 Hz, 1H), 7.72-7.60 (m, 4H), 6.12 (s, 2H), 3.74-3.65 (m, 4H), 3.37-3.22 (m, 2H), 2.16-1.40 (m, 10H), 1.06-0.97 (m, 2H), 0.00 (s, 9H). LCMS (Method B): RT=2.96 min, M+H+=524.

후처리

  1. additionOn complete addition
  2. temperatureto cool to ambient temperature
  3. concentrationThe mixture was concentrated in vacuo
  4. customthe resultant residue was purified by flash chromatography (silica, 50 g column, Biotage, 0-5% MeOH in DCM)

출처 및 근거

ORD 기록
ord-48f8b335f83742fd90060526a851f085
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09216980B2

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