Diisopropylethylamine → HCID 67387290, compound

HRID 2408827Notes

Reaction equation

HRID 2408827 reaction equation
[O:1]=[C:2]1[C:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][N:3]1[CH2:20][C:21]([OH:23])=O.[NH2:24][CH:25]1[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][CH2:26]1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>ClCCl>[O:1]=[C:2]1[C:7]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH2:6][CH2:5][CH2:4][N:3]1[CH2:20][C:21]([NH:24][CH:25]1[CH2:26][CH2:27][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:29][CH2:30]1)=[O:23]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 12682914-Amino-1-Boc-piperidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 673592802-(2-Oxo-3,3-diphenylpiperidin-1-yl)acetic acid

Product 1

HCID 67387290HCID 67387290, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-(2-oxo-3,3-diphenylpiperidin-1-yl)acetic acid, obtained in Example 1E (0.95 g, 3.08 mmol) and tert-butyl 4-aminopiperidine-1-carboxylate (CAS 87120-72-7) in dichloromethane (10 mL) was added O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (1.171 g, 3.08 mmol) and diisopropylethylamine (2.6 mL, 13.86 mmol). The reaction mixture was stirred at ambient temperature overnight, then diluted with dichloromethane and washed with 1 N HCl (10 mL), water, 1 N NaOH (10 mL), water, dried over MgSO4, and evaporated to yield tert-butyl 4-(2-(2-oxo-3,3-diphenylpiperidin-1-yl)acetamido)piperidine-1-carboxylate (0.8 g, 60%). To a solution of this product in methanol (10 mL) was added 4 N HCl/dioxane (2 mL), and the reaction mixture was stirred at room temperature for 3 hours. It was concentrated in vacuo and partitioned between 1 N NaOH and dichloromethane. The organic layer was concentrated and chromatographed on an Analogix 15-24 g silica column, eluting with a 2-5% gradient of methanol/dichloromethane to yield the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.19-7.35 (m, 10H), 6.99 (d, J=6.4 Hz, 1H), 4.01 (s, 2H), 3.75-3.95 (m, 1H), 3.52 (t, J=6.6 Hz, 2H), 3.04-3.14 (m, 2H), 2.63-2.72 (m, 2H), 2.57-2.64 (m, 2H), 1.77-1.95 (m, 4H), 1.37-1.53 (m, 2H); MS (ESI+) m/z 392 (M+H)+.

Workup

  1. washwashed with 1 N HCl (10 mL), water, 1 N NaOH (10 mL), water
  2. dry with materialdried over MgSO4
  3. customevaporated

Sources & evidence

ORD record
ord-42274408411b4d7aad25d9536c8ca389
Source dataset
uspto-grants-2014_08
Patent number
US08815869B2

Reaction notes

Loading…