Ammonia → (R)-1-(2-(5-methylisoxazole-3-carboxamido)-4-((1-phenylethylamino)methyl)phenyl)piperidine-4-carboxamide

HRID 1801589Notes

Reaction equation

HRID 1801589 reaction equation
[CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]([NH:9][C:10]2[CH:15]=[C:14]([CH2:16][NH:17][C@@H:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH3:19])[CH:13]=[CH:12][C:11]=2[N:26]2[CH2:31][CH2:30][CH:29]([C:32](OC)=[O:33])[CH2:28][CH2:27]2)=[O:8])[CH:3]=1.[NH3:36]>>[CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]([NH:9][C:10]2[CH:15]=[C:14]([CH2:16][NH:17][C@@H:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH3:19])[CH:13]=[CH:12][C:11]=2[N:26]2[CH2:31][CH2:30][CH:29]([C:32]([NH2:36])=[O:33])[CH2:28][CH2:27]2)=[O:8])[CH:3]=1

Participants

3

Reactant 2

HCID 222AmmoniaHCID 59803195(R)-methyl 1-(2-(5-methylisoxazole-3-carboxamido)-4-((1-phenylethylamino)methyl)phenyl)piperidine-4-carboxylate

Product 1

HCID 59803175(R)-1-(2-(5-methylisoxazole-3-carboxamido)-4-((1-phenylethylamino)methyl)phenyl)piperidine-4-carboxamideYield 23%

Conditions

Temperature
75 °C

Procedure

To (R)-methyl 1-(2-(5-methylisoxazole-3-carboxamido)-4-((1-phenylethylamino)methyl)phenyl)piperidine-4-carboxylate 61 (0.220 g, 0.46 mmol) was added ammonia (2 M in MeOH, 50 mL). The reaction mixture was heated to 75° C. in a sealed tube for 7 d, and concentrated in vacuo. Purification by flash column chromatography on silica gel (1% to 10% MeOH (2 M NH3) in DCM) gave (R)-1-(2-(5-methylisoxazole-3-carboxamido)-4-((1-phenylethylamino)methyl)phenyl)piperidine-4-carboxamide 62 (0.048 g, 23% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 1.26 (d, J=6.7 Hz, 3H), 1.76-1.84 (m, 4H), 2.24 (m, 1H), 2.52 (s, 3H), 2.67 (t, J=8.8 Hz, 2H), 2.95 (d, J=11.5 Hz, 2H), 3.43 (d, J=13.3 Hz, 1H), 3.48 (d, J=13.7 Hz, 1H), 3.71 (q, J=6.5 Hz, 1H), 6.71 (s, 1H), 7.19 (s, 1H), 7.05 (d, J=8.1 Hz, 1H), 7.20 (d, J=8.1 Hz, 1H), 7.22 (d, J=3.9 Hz, 1H), 7.31-7.38 (m, 6H), 8.22 (s, 1H), 9.73 (s, 1H). Mass spectrum: calculated for C26H31N5O3 461.2. found 462.3 (M++1).

Workup

  1. concentrationconcentrated in vacuo
  2. customPurification by flash column chromatography on silica gel (1% to 10% MeOH (2 M NH3) in DCM)

Sources & evidence

ORD record
ord-d85ebcd2364348a8b02468c94438f492
Source dataset
uspto-grants-2013_01
Patent number
US08349831B2

Reaction notes

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