Dimethylformamide → Ammonium Hydroxide

HRID 1630789노트

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HRID 1630789 반응식
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]1[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][CH:13]=1)[C:6]([C:20]1[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=1)=[C:5]2[CH3:26].[N-:27]=[N+:28]=[N-:29].[Na+].[Cl-].[NH4+].CN(C=[O:37])C>>[NH4+:7].[OH-:37].[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]1[CH:13]=[CH:14][C:15]([C:16]3[N:27]=[N:28][NH:29][N:17]=3)=[CH:18][CH:19]=1)[C:6]([C:20]1[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=1)=[C:5]2[CH3:26]

참가 물질

6

반응물 4

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 33557Sodium AzideHCID 582156974-(5-chloro-3-methyl-2-pyridin-3-yl-1H-indol-1-ylmethyl)-benzonitrile

생성물 2

HCID 14923Ammonium Hydroxide수율 0.1%HCID 582157675-chloro-3-methyl-2-pyridin-3-yl-1-[4-(2H-tetrazol-5-yl)-benzyl]-1H-indole

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온도
120 °C

실험 절차

To a solution of 4-(5-chloro-3-methyl-2-pyridin-3-yl-indol-1-ylmethyl)-benzonitrile (Example 17, 179 mg, 0.5 mmol) in DMF (5 mL) is added sodium azide (97 mg, 1.5 mmol) and ammonium chloride (80 mg, 1.5 mmol) and the mixture is heated to 120° C. The reaction mixture is cooled to room temperature and filtered. The filtrate is purified by reverse phase HPLC with Xbridge C18 and a gradient of 0.1% NH4OH in acetonitrile to give 5-chloro-3-methyl-2-pyridin-3-yl-1-[4-(2H-tetrazol-5-yl)-benzyl]-1H-indole. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.21 (s, 3H), 5.34 (s, 2H), 6.81 (d, J=8.1 Hz, 2H), 7.11 (br. s, 1H), 7.17 (dd, J=8.7, 2.1 Hz, 1H), 7.48-7.53 (m, 2H), 7.67 (d, J=2.0 Hz, 1H), 7.77 (d, J=8.3 Hz, 2H), 7.80-7.84 (m, 1H), 8.60 (d, J=1.5 Hz, 1H), 8.62 (dd, J=4.8, 1.5 Hz, 1H). HRMS (ESI) m/z 401.1276 [(M+H)+ Calcd for C22H18N6Cl: 401.1281].

후처리

  1. temperatureThe reaction mixture is cooled to room temperature
  2. filtrationfiltered
  3. customThe filtrate is purified by reverse phase HPLC with Xbridge C18

출처 및 근거

ORD 기록
ord-26d260b1620f4e5f8401a324831f7d18
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08791141B2

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