4-Piperidinamine → N-(4-(3-fluorobenzyloxy)-3-chlorophenyl)-5-((4-aminopiperidin-1-yl)methyl)pyrrolo[1,2-f][1,2,4]triazin-4-amine

HRID 1829917Notes

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:25]=[CH:24][C:23]([O:26][CH2:27][C:28]4[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[CH:29]=4)=[C:22]([Cl:35])[CH:21]=2)=[N:16][CH:15]=[N:14]3)=O)C=CC=CC=1.[NH2:36][CH:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1>C(Cl)Cl>[NH2:36][CH:37]1[CH2:42][CH2:41][N:40]([CH2:9][C:10]2[CH:11]=[CH:12][N:13]3[C:18]=2[C:17]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH2:27][C:28]4[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[CH:29]=4)=[C:22]([Cl:35])[CH:21]=2)=[N:16][CH:15]=[N:14]3)[CH2:39][CH2:38]1

Participants

Conditions

Temperature: 135 °C

Procedure

A mixture of the sulfoxide 7B (100 mg, 0.20 mmol) and 4-aminopiperidine (0.6 gm, 6 mmol) was heated in a sealed tube at 135° C. for 4 hr. 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 7C (40 mg, 42%) as a foam. Analytical HPLC retention time=1.35 min. (YMC Xterra S7 C18, 3.0×50 mm column, 10–90% aqueous methanol over 2 minutes containing 0.1% TFA, 5 mL/min, monitoring at 220 nm) and a LC/MS M++1=481.

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-f59592f7d0414f7d9f06ffdffb18f64e
Source dataset: uspto-grants-2006_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07064203B2

Reaction notes

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