1,4'-Bipiperidine → HCID 58864471, compound

HRID 2355855Notes

Reaction equation

HRID 2355855 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:27]=[C:28]4[C:32](=[CH:33][CH:34]=3)[N:31]([S:35]([CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])(=[O:37])=[O:36])[N:30]=[CH:29]4)[C:22](O)=[O:23])=[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(CC)C(C)C)(C)C.[N:53]1([CH:59]2[CH2:64][CH2:63][NH:62][CH2:61][CH2:60]2)[CH2:58][CH2:57][CH2:56][CH2:55][CH2:54]1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[N:53]1([CH:59]2[CH2:64][CH2:63][N:62]([C:22](=[O:23])[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])[CH2:25][C:26]3[CH:27]=[C:28]4[C:32](=[CH:33][CH:34]=3)[N:31]([S:35]([CH2:38][CH2:39][Si:40]([CH3:43])([CH3:41])[CH3:42])(=[O:36])=[O:37])[N:30]=[CH:29]4)[CH2:61][CH2:60]2)[CH2:58][CH2:57][CH2:56][CH2:55][CH2:54]1

Participants

6

Reactant 4

HCID 786071,4'-BipiperidineHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 58864337HCID 58864337, compound

Product 1

HCID 58864471HCID 58864471, compoundYield 87.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (R)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-3-[1-(2-trimethylsilanyl-ethanesulfonyl)-1H-indazol-5-yl]-propionic acid (554 mg, 0.88 mmol) and N,N-diisopropylethylamine (0.62 mL, 3.54 mmol) in methylene chloride (20 mL) was added a solution of 4-piperidinopiperidine (164 mg, 0.97 mmol) and PyBOP® (460 mg, 0.88 mmol) in methylene chloride (15 mL). The reaction mixture was stirred for 16 h at room temperature. It was then concentrated to approximately 2 mL and subjected to flash column chromatography using methylene chloride/methanol/triethylamine (94:5:1) as eluent to give 599 mg (87%) of the title compound as a white solid. 1H-NMR (CD3CN, 300 MHz) δ 8.37 (s, 0.5H), 8.36 (s, 0.5H), 8.02-7.96 (m, 1H), 7.74 (s, 0.5H), 7.71 (s, 0.5H), 7.55-7.46 (m, 1H), 7.21-7.12 (m, 2H), 6.97-6.92 (m, 1H), 6.79 (d, J=8.1 Hz, 1H), 5.71 (t, J=8.1 Hz, 1H), 5.00 (dd, J=15.0, 8.1 Hz, 1H), 4.63-4.51 (m, 1H), 4.39-4.29 (m, 1H), 4.29 (s, 2H), 4.10-3.96 (m, 3H), 3.46-3.40 (m, 2H), 2.92-2.70 (m, 8H), 2.58-2.37 (m, 5H), 1.74-1.40 (m, 13H), 0.80-0.74 (m, 2H), −0.04 (s, 9H). Mass spec.: 778 (MH)+.

Workup

  1. concentrationIt was then concentrated to approximately 2 mL

Sources & evidence

ORD record
ord-653e5bf5b9114d8e8b4dd9386a50a706
Source dataset
uspto-grants-2010_07
Patent number
US07754732B2

Reaction notes

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