Cyclopentylamine → 1-[3-(4-Chloro-benzoylamino)-benzyl]-piperidine-4-carboxylic acid cyclopentylamide

HRID 1486728Notes

Reaction equation

[CH:1]1([NH2:6])[CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:7][C:8]1[CH:32]=[CH:31][C:11]([C:12]([NH:14][C:15]2[CH:16]=[C:17]([CH:28]=[CH:29][CH:30]=2)[CH2:18][N:19]2[CH2:24][CH2:23][CH:22]([C:25](O)=[O:26])[CH2:21][CH2:20]2)=[O:13])=[CH:10][CH:9]=1.C1C=NC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1.CCN(C(C)C)C(C)C.CCN(C(C1C=CC=C(C)C=1)=O)CC>CN(C=O)C>[CH:1]1([NH:6][C:25]([CH:22]2[CH2:21][CH2:20][N:19]([CH2:18][C:17]3[CH:28]=[CH:29][CH:30]=[C:15]([NH:14][C:12](=[O:13])[C:11]4[CH:31]=[CH:32][C:8]([Cl:7])=[CH:9][CH:10]=4)[CH:16]=3)[CH2:24][CH2:23]2)=[O:26])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

Conditions

Temperature: 50 °C

Procedure

1-Cyclopentylamine (10.7 mg, 0.124 mmol) is added to a solution of [3-(4-chloro-benzoylamino)-benzyl]-piperidine-4-carboxylic acid (35.4 mg, 0.095 mmol) in DMF (0.5 mL). The resulting solution is treated with a solution of HOAT (15.5 mg, 0.114 mmol) in DMF (0.5 mL) followed by si-DCC (200 mg, 0.95 mmol/g, 0.19 mmol), and DIPEA (0.033 mL, 0.19 mmol). The mixture is stirred at 50° C. overnight. PI-DETA (7.99 mmol/g, 0.3 mmol, 37 mg) is added to the solution in order to scavenge the acid, PI-NCO (2.24 mmol/g, 0.3 mmol, 130 mg) is added to scavenge the amine in excess and the mixture is stirred for 1 h. The resin is filtered and washed with a mixture of MeOH/DCM 1:1, (4×1 mL). The resulting solution is evaporated under HV. The title compound is obtained by prep. HPLC F as a colourless powder: LC-MS A: tR=1.21 min; [M+H]+=440.1.

Workup

additionis added
stirringis stirred for 1 h
filtrationThe resin is filtered
washwashed with a mixture of MeOH/DCM 1:1, (4×1 mL)
customThe resulting solution is evaporated under HV

Sources & evidence

ORD record: ord-53983610fcaf4968b472859bc7f491ce
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09428456B2

Reaction notes

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