1,1'-Carbonyldiimidazole → HCID 118317160, compound

HRID 2283233Notes

Reaction equation

[C:1]([NH:4][CH2:5][C:6]1[CH:7]=[C:8]([N:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]2)[CH:9]=[CH:10][C:11]=1[NH2:12])(=[O:3])C.NC1C=CC(N2CCN(C(OC(C)(C)C)=O)CC2)=CC=1CN.C1N=CN(C(N2C=NC=C2)=O)C=1>C1COCC1>[O:3]=[C:1]1[NH:4][CH2:5][C:6]2[C:11](=[CH:10][CH:9]=[C:8]([N:13]3[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:23])[CH3:24])=[O:20])[CH2:15][CH2:14]3)[CH:7]=2)[NH:12]1

Participants

Conditions

Temperature: 80 °C

Procedure

Therefore an alternative approach was adopted in which benzaldehyde 11 was nitrated to the known benzaldehyde 12, which in turn was subjected to reductive amination by condensing it with ammonium hydroxide, using sodium borohydride as reducing agent to produce amine 13 in high yield. Acetylation amine 13 generated acetamide 14, which was reacted with tert-butyl piperazine-1-carboxylate under Buchwald-Hartwig conditions to afford intermediate 15 in good yield. Reduction of nitro group of 15 over Pd—C in a Parr apparatus produced intermediate 16 in 91% yield high yield. Exposure of intermediate 16 under basic conditions rendered the desired diamine 17 in good yield after column purifications. Reaction of 17 with CDI in THF, heating the mixture at 80° C. for 6 hours, gave access to the key intermediate 10 in an overall yield of 33% from 14. Exposure of intermediate 10 to trifluoroacetic acid in a mixture of methanol and dichloromethane finally furnished the desired key intermediate 18 (scheme 2).

Workup

customin good yield after column purifications

Sources & evidence

ORD record: ord-61292511a40846f7a8846907e66f6a91
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09145388B2

Reaction notes

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