Formic Acid → 2-[2,4-Dioxo-5-phenyl-3-(4,5,6,7-tetrahydro-1H-indazol-3-ylmethyl)-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(4-methoxy-phenyl)-acetamide

HRID 343222노트

반응식

HRID 343222 반응식
[O:1]=[C:2]1[N:8]([CH2:9][C:10]([N:12]([CH:21]([CH3:23])[CH3:22])[C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)=[O:11])[C:7]2[CH:24]=[CH:25][CH:26]=[CH:27][C:6]=2[N:5]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:4](=[O:34])[CH:3]1[CH2:35][C:36]1[C:44]2[CH2:43][CH2:42][CH2:41][CH2:40][C:39]=2[N:38](CC2C=CC=CC=2)[N:37]=1.C(O)=O>C(O)C.[Pd]>[O:1]=[C:2]1[N:8]([CH2:9][C:10]([N:12]([CH:21]([CH3:22])[CH3:23])[C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)=[O:11])[C:7]2[CH:24]=[CH:25][CH:26]=[CH:27][C:6]=2[N:5]([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[C:4](=[O:34])[CH:3]1[CH2:35][C:36]1[C:44]2[CH2:43][CH2:42][CH2:41][CH2:40][C:39]=2[NH:38][N:37]=1

참가 물질

5

반응물 2

HCID 284Formic AcidHCID 106045852-[2,4-Dioxo-5-phenyl-3-(4,5,6,7-tetrahydro-1-benzyl-1H-indazol-3-ylmethyl)-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(4-methoxy-phenyl)-acetamide

생성물 1

HCID 108172412-[2,4-Dioxo-5-phenyl-3-(4,5,6,7-tetrahydro-1H-indazol-3-ylmethyl)-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(4-methoxy-phenyl)-acetamide수율 80.7%

시약·촉매·용매 2

HCID 23938Palladium촉매HCID 702Ethanol용매

실험 절차

To a stirring solution of 150 mg (0.22 mmol) of 2-[2,4-Dioxo-5-phenyl-3-(4,5,6,7-tetrahydro-1-benzyl-1H-indazol-3-ylmethyl)-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(4-methoxy-phenyl)-acetamide, prepared as in Intermediate 52, in 10 mL of a 10% solution of formic acid in absolute ethanol is added 150 mg of 10% palladium on carbon. The resulting black suspension is refluxed for 3 h, then cooled to RT. The reaction mixture is filtered through Celite to remove the catalyst and the solvent removed in vacuo. Purification of the residue via silica gel MPLC using an Si60 column and hexane/EtOAc 1/5 as eluent afforded 105 mg of the title compound as a white solid: mp 170°-173° C.; 1H NMR (CDCl3, 400 MHz) δ7.38-6.88 (m, 13H), 5.03 (m, 1H), 4.34 (d, 1H, J=16.8), 4.14 (d, 1H, J=16.8), 3.84(s, 3H), 3.58 (dd, 1H, J=6.8, 6.8), 3.46 (dd, 1H, J=7.0, 14.0), 3.30 (dd, 1H, J=7.5, 15.2), 2.60 (m, 2H), 2.36 (m, 2H), 1.70 (m, 4H), 1.08 (2×d, 6H, J=6.6); low resolution MS (FAB)m/e 592 (MH+), 591 (M+), 427; Anal. (C35H37N5O4) Calcd. C, 71.05; H, 6.30; N, 11.84; Found C, 70.20; H, 6.47; N, 11.66.

후처리

  1. temperatureThe resulting black suspension is refluxed for 3 h
  2. filtrationThe reaction mixture is filtered through Celite
  3. customto remove the catalyst
  4. customthe solvent removed in vacuo
  5. customPurification of the residue via silica gel MPLC

출처 및 근거

ORD 기록
ord-e5651b9f3b15467497dda4dec420d3c2
출처 데이터셋
uspto-grants-1999_01
특허 번호
US05859007

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