Triethylamine → [5-(6,6-Difluoro-[1,4]diazepan-1-ylmethyl)-pyrrolo[2,1-f][1,2,4]triazin-4-yl]-[1-(3-fluoro-benzyl)-1H-indazol-5-yl]-amine

HRID 1072090Notes

Reaction equation

CS(OS(C)(=O)=O)(=O)=O.[F:10][C:11]1[CH:12]=[C:13]([CH:36]=[CH:37][CH:38]=1)[CH2:14][N:15]1[C:23]2[C:18](=[CH:19][C:20]([NH:24][C:25]3[C:30]4=[C:31]([CH2:34]O)[CH:32]=[CH:33][N:29]4[N:28]=[CH:27][N:26]=3)=[CH:21][CH:22]=2)[CH:17]=[N:16]1.C(N(CC)CC)C.[F:46][C:47]1([F:54])[CH2:53][NH:52][CH2:51][CH2:50][NH:49][CH2:48]1>C(Cl)Cl.ClCCCl>[F:46][C:47]1([F:54])[CH2:53][N:52]([CH2:34][C:31]2[CH:32]=[CH:33][N:29]3[C:30]=2[C:25]([NH:24][C:20]2[CH:19]=[C:18]4[C:23](=[CH:22][CH:21]=2)[N:15]([CH2:14][C:13]2[CH:36]=[CH:37][CH:38]=[C:11]([F:10])[CH:12]=2)[N:16]=[CH:17]4)=[N:26][CH:27]=[N:28]3)[CH2:51][CH2:50][NH:49][CH2:48]1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of methanesulfonic anhydride (114 mg, 3.2 equiv.) in DCM (0.6 mL) was added to a solution of {4-[1-(3-fluoro-benzyl)-1H-indazol-5-ylamino]-pyrrolo[2,1-f][1,2,4]triazin-5-yl}-methanol (78 mg, 2 mmole) in dry DCM (1.4 mL) at 0° C. under nitrogen followed by triethylamine (0.140 mL, 5 equiv.). After stirring at 0° C. for 1 hr, 6,6-difluoro-[1,4]diazepane (82 mg, 3 equiv.) and 1,2 dichloroethane (2 mL) were added. The reaction mixture was transferred to a microwave reactor (Personal Chemistry's Smith Creator) and irradiated at 65° C. for 50 min. Removal of the solvent followed by preparative HPLC afforded the title compound as a solid (29 mg, 29%). MS: 507 (M+H+); HPLC Ret Time: 1.47 min (YMC Xterra ODS S7 3.0×50 mm column, 2 min gradient, 5 ml/min).

Workup

customThe reaction mixture was transferred to a microwave reactor
custom(Personal Chemistry's Smith Creator) and irradiated at 65° C. for 50 min
customRemoval of the solvent

Sources & evidence

ORD record: ord-ea345d90d001405c9e51590139481d93
Source dataset: uspto-grants-2005_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06908916B2

Reaction notes

Loading…