Hexahydro-1,4-diazepine → [5-[([1,4]Diazepan-1-yl)methyl]pyrrolo[2,1-f][1,2,4]triazin-4-yl][1-(3-fluorobenzyl)-1H-indazol-5-yl]amine

HRID 1072072Notes

Reaction equation

C1(S([CH2:9][C:10]2[CH:11]=[CH:12][N:13]3[C:18]=2[C:17]([NH:19][C:20]2[CH:21]=[C:22]4[C:26](=[CH:27][CH:28]=2)[N:25]([CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[CH:31]=2)[N:24]=[CH:23]4)=[N:16][CH:15]=[N:14]3)=O)C=CC=CC=1.[NH:37]1[CH2:43][CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1>C(Cl)Cl>[N:37]1([CH2:9][C:10]2[CH:11]=[CH:12][N:13]3[C:18]=2[C:17]([NH:19][C:20]2[CH:21]=[C:22]4[C:26](=[CH:27][CH:28]=2)[N:25]([CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[CH:31]=2)[N:24]=[CH:23]4)=[N:16][CH:15]=[N:14]3)[CH2:43][CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1

Participants

Conditions

Temperature: 135 °C

Procedure

A mixture of (5-benzenesulfinylmethyl-pyrrolo[2,1-f][1,2,4]triazin-4-yl)-[1-(3-fluoro-benzyl)-1H-indazol-5-yl]-amine (50 mg, 0.101 mmole) and homopiperazine (300 mg, 30 equiv) in a sealed tube was heated at 135° C. overnight. The reaction mixture was taken up in DCM, washed with water, and dried (Na2SO4). Removal of the solvent followed by radial chromatography (2 mm silica gel plate eluted with DCM containing 5% MeOH) afforded the title compound as a foam (39 mg, 82%). 1H NMR (CDCl3) δ 1.85 (m, 2H), 2.96 (m, 8H), 3.91 (s, 2H), 5.58 (s, 2H), 6.50 (d, 1H, J=3 Hz), 6.8-7.6 (m, 7H), 7.89 (s, 1H), 8.05 (d, 1H, J=1 Hz), 8.11 (d, 1H, J=2 Hz); MS: 471 (M+H)+; HPLC Ret Time: 1.09 min (YMC Xterra ODS S7, 3.0×50 mm column, 2 min gradient, 5 mL/min).

Workup

washwashed with water
dry with materialdried (Na2SO4)
customRemoval of the solvent
washfollowed by radial chromatography (2 mm silica gel plate eluted with DCM containing 5% MeOH)

Sources & evidence

ORD record: ord-ab5939a700234f76ae52ca7201cb6d70
Source dataset: uspto-grants-2005_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06908916B2

Reaction notes

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