Diisopropylethylamine → N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-({4-methyl-1-[2-(piperazin-1-yl)ethyl]piperidin-4-yl}methyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide

HRID 715840노트

반응식

HRID 715840 반응식
[N:1]1[CH:2]=[CH:3][N:4]2[CH:9]=[CH:8][C:7]([CH2:10][NH:11][C:12]([C:14]3[S:15][C:16]([C:19]4[CH:20]=[N:21][N:22]([CH2:24][C:25]5([CH3:31])[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]5)[CH:23]=4)=[CH:17][CH:18]=3)=[O:13])=[CH:6][C:5]=12.Br[CH2:33][CH2:34][N:35]1[CH2:40][CH2:39][N:38](C(OC(C)(C)C)=O)[CH2:37][CH2:36]1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[N:1]1[CH:2]=[CH:3][N:4]2[CH:9]=[CH:8][C:7]([CH2:10][NH:11][C:12]([C:14]3[S:15][C:16]([C:19]4[CH:20]=[N:21][N:22]([CH2:24][C:25]5([CH3:31])[CH2:30][CH2:29][N:28]([CH2:33][CH2:34][N:35]6[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]6)[CH2:27][CH2:26]5)[CH:23]=4)=[CH:17][CH:18]=3)=[O:13])=[CH:6][C:5]=12

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 15946441tert-Butyl 4-(2-bromoethyl)piperazine-1-carboxylateHCID 86702099N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(4-methylpiperidin-4-yl)methyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide

생성물 1

HCID 72699871N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-({4-methyl-1-[2-(piperazin-1-yl)ethyl]piperidin-4-yl}methyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A solution of N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(4-methylpiperidin-4-yl)methyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide (0.100 g, 0.197 mmol) in N,N-dimethylformamide (2 ml) was added tert-butyl 4-(2-bromoethyl)piperazine-1-carboxylate (0.058 g, 0.197 mmol) followed by N,N-diisopropylethylamine (0.138 ml, 0.788 mmol) and the reaction was stirred overnight. The reaction mixture was purified directly using normal phase chromatography and the resulting material was treated with HCl in dioxane (4M) for 2 hours then concentrated to give the title compound as a hydrochloride salt. 1H NMR (500 MHz, DMSO-d6) δ 14.64 (s, 1H), 10.40 (s, 1H), 9.72 (s, 1H), 9.54 (t, J=6.0 Hz, 1H), 8.89 (d, J=6.9 Hz, 1H), 8.34 (d, J=1.8 Hz, 1H), 8.22 (s, 1H), 8.16 (d, J=2.1 Hz, 1H), 7.91 (d, J=3.9 Hz, 1H), 7.87 (s, 1H), 7.83 (s, 1H), 7.50 (dd, J=7.0, 1.4 Hz, 1H), 7.28 (d, J=3.8 Hz, 1H), 4.64 (d, J=5.8 Hz, 2H), 4.23-3.54 (m, 10H), 3.35 (d, J=38.3 Hz, 8H), 1.72 (d, J=77.7 Hz, 4H), 0.98 (s, 3H); MS (ESI(+)) m/e 547 (M+H)+.

후처리

  1. customThe reaction mixture was purified directly
  2. additionthe resulting material was treated with HCl in dioxane (4M) for 2 hours
  3. concentrationthen concentrated

출처 및 근거

ORD 기록
ord-79e63527a784485c8829dff368f136d8
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09187472B2

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