Tert-butyl octahydropyrrolo(3,4-c)pyrrole-2-carboxylate → tert-Butyl 5-[3-(2-aminopyrid-4-yl)-2-(4-chlorophenyl)imidazo[1,2-b]pyridazin-6-yl]hexahydropyrrolo[3,4-c]pyrrole-2-carboxylate

HRID 80730

Reaction equation

Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:18]3[CH:23]=[CH:22][N:21]=[C:20]([NH2:24])[CH:19]=3)=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=3)[N:10]=2)[N:7]=1.[CH2:25]1[CH:29]2[CH2:30][NH:31][CH2:32][CH:28]2[CH2:27][N:26]1[C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34]>C(O)CCCC>[NH2:24][C:20]1[CH:19]=[C:18]([C:8]2[N:6]3[N:7]=[C:2]([N:31]4[CH2:30][CH:29]5[CH2:25][N:26]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:27][CH:28]5[CH2:32]4)[CH:3]=[CH:4][C:5]3=[N:10][C:9]=2[C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)[CH:23]=[CH:22][N:21]=1

Participants

Conditions

Temperature: 135 °C

Procedure

A mixture of 0.15 g (0.42 mmol) of 4-[6-chloro-2-(4-chlorophenyl)imidazo[1,2-b]pyridazin-3-yl]pyrid-2-ylamine and 0.36 g (1.7 mmol) of tert-butyl hexahydropyrrolo[3,4-c]pyrrole-2-carboxylate in 7 mL of pentanol is stirred at 135° C. for 20 hours. The solvent is then evaporated off under reduced pressure and the oily residue is chromatographed on a column of silica gel, eluting with a stepwise gradient of methanol and aqueous ammonia in dichloromethane (0:0:100 to 2:1:98). 0.16 g of product is isolated after trituration in diisopropyl ether, filtering off and drying under reduced pressure.

Workup

customThe solvent is then evaporated off under reduced pressure
customthe oily residue is chromatographed on a column of silica gel
washeluting with a stepwise gradient of methanol and aqueous ammonia in dichloromethane (0:0:100 to 2:1:98)

Sources & evidence

ORD record: ord-2a30010c88fe4cd29478672b484c4d43
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846676B2

Linked notes

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