1,4'-Bipiperidine → HCID 178523850, compound

HRID 2355969Notes

Reaction equation

HRID 2355969 reaction equation
[O:1]=[C:2]1[N:11]([CH:12]2[CH2:17][CH2:16][N:15]([C:18]([NH:20][C@H:21]([CH2:25][C:26]3[CH:38]=[CH:37][C:29]4[NH:30][C:31]([C:33]([F:36])([F:35])[F:34])=[N:32][C:28]=4[CH:27]=3)[C:22]([OH:24])=O)=[O:19])[CH2:14][CH2:13]2)[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[NH:3]1.C(N(C(C)C)CC)(C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[N:81]1([CH:87]2[CH2:92][CH2:91][NH:90][CH2:89][CH2:88]2)[CH2:86][CH2:85][CH2:84][CH2:83][CH2:82]1>C(Cl)Cl>[F:34][C:33]([F:36])([F:35])[C:31]1[NH:30][C:29]2[CH:37]=[CH:38][C:26]([CH2:25][C@@H:21]([NH:20][C:18]([N:15]3[CH2:16][CH2:17][CH:12]([N:11]4[CH2:10][C:9]5[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=5)[NH:3][C:2]4=[O:1])[CH2:13][CH2:14]3)=[O:19])[C:22](=[O:24])[N:90]3[CH2:91][CH2:92][CH:87]([N:81]4[CH2:86][CH2:85][CH2:84][CH2:83][CH2:82]4)[CH2:88][CH2:89]3)=[CH:27][C:28]=2[N:32]=1

Participants

6

Reactant 4

HCID 786071,4'-BipiperidineHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 178525805HCID 178525805, compound

Product 1

HCID 178523850HCID 178523850, compoundYield 12%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of the acid (R)-2-(4-(1,2-dihydro-2-oxoquinazolin-3(4H)-yl)piperidine-1-carboxamido)-3-(2-(trifluoromethyl)-1H-benzo[d]imidazol-5-yl)propanoic acid (33 mg, 0.06 mmol) and diisopropylethylamine (33 mg, 0.25 mmol) in methylene chloride (2 mL) was added a solution of PyBOP (33 mg, 0.06 mmol) and 4-piperidinopiperidine (12 mg, 0.07 mmol) in methylene chloride (1 mL). The reaction mixture was stirred at room temperature for 16 h and was subjected to preparative thin layer chromatography for purification (1:10 2M ammonia in methanol/methylene chloride) to give the title compound (4.6 mg, 12% yield). 1H-NMR (CD3OD, 500 MHz) δ 7.73-7.71 (m, 1H), 7.62 (bs, 1H), 7.39-7.36 (m, 1H), 7.19-7.11 (m, 2H), 6.96 (t, J=7.2 Hz, 1H), 6.81 (d, J=7.9 Hz, 1H), 5.06-5.02 (m, 1H), 4.67-4.58 (m, 1H), 4.49-4.40 (m, 1H), 4.38 (s, 1H), 4.33 (bs, 1H), 4.25-4.16 (m, 2H), 4.10-4.03 (m, 1H), 3.22-3.14 (m, 3H), 3.04-2.87 (m, 4H), 2.79-2.71 (m, 1H), 2.58-2.48 (m, 1H), 2.44-2.33 (m, 1H), 2.31-2.22 (m, 1H), 2.04-1.92 (m, 1H), 1.86-1.43 (m, 11H), 1.33-1.29 (m, 1H), 0.94-0.84 (m, 1H), −0.04-−0.12 (m, 1H). LC/MS: tR=1.97 min, 681 (MH)+.

Workup

  1. customwas subjected to preparative thin layer chromatography for purification (1:10 2M ammonia in methanol/methylene chloride)

Sources & evidence

ORD record
ord-9b0f5a01fdb84abb9b7e9154102c11f9
Source dataset
uspto-grants-2010_07
Patent number
US07754732B2

Reaction notes

Loading…