2-bromo-N-tert-butyl-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide → N-tert-butyl-2-(6-fluoro-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

HRID 246754노트

반응식

HRID 246754 반응식
Br[C:2]1[N:7]=[C:6]2[C:8]([C:30]([NH:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[CH:9][N:10]([C:11]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:5]2=[N:4][CH:3]=1.[F:37][C:38]1[CH:46]=[C:45]2[C:41]([C:42]([Sn](CCCC)(CCCC)CCCC)=[N:43][NH:44]2)=[CH:40][CH:39]=1>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[C:33]([NH:32][C:30]([C:8]1[C:6]2=[N:7][C:2]([C:42]3[C:41]4[C:45](=[CH:46][C:38]([F:37])=[CH:39][CH:40]=4)[NH:44][N:43]=3)=[CH:3][N:4]=[C:5]2[N:10]([C:11]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:9]=1)=[O:31])([CH3:35])([CH3:34])[CH3:36]

참가 물질

6

반응물 2

HCID 866780082-bromo-N-tert-butyl-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamideHCID 1784482326-fluoro-3-(tributylstannyl)-1H-indazole

생성물 1

HCID 71280404N-tert-butyl-2-(6-fluoro-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide수율 27%

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418397HCID 178418397, 화합물촉매HCID 6228Dimethylformamide용매

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온도
85 °C

실험 절차

In a round-bottomed flask, 2-bromo-N-tert-butyl-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (600 mg, 1.12 mmol) and 6-fluoro-3-(tributylstannyl)-1H-indazole (475 mg, 1.12 mmol) were dissolved in DMF (10 mL) under nitrogen. Pd(PPh3)4 (65 mg, 0.056 mmol) and CuI (43 mg, 0.224 mmol) were added and the mixture sonicated for 5 min while bubbling nitrogen. The reaction mixture was stirred at 85° C. for 16 hours. After solvent removal, the concentrated mixture was purified by column chromatography on silica gel eluting with petroleum ether/EtOAc (3:1 v/v) to give N-tert-butyl-2-(6-fluoro-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (180 mg, 27%) as a white solid. LCMS: (M+H)+=595; 1H NMR (300 MHz, DMSO): δ 13.60 (s, 1H), 8.78 (s, 1H), 8.45-8.40 (m, 1H), 8.01 (s, 1H), 7.95 (s, 1H), 7.45-7.33 (m, 10H), 7.21-7.09 (m, 7H), 1.50 (s, 9H).

후처리

  1. customthe mixture sonicated for 5 min
  2. customwhile bubbling nitrogen
  3. customAfter solvent removal
  4. customthe concentrated mixture was purified by column chromatography on silica gel eluting with petroleum ether/EtOAc (3:1 v/v)

출처 및 근거

ORD 기록
ord-d57040aa1a194223b5861539b724d9d9
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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