N,N-dimethyl-2-thioxo-2,3-dihydrobenzo[d]oxazole-6-carboxamide → (R)-N,N-dimethyl-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]oxazole-6-carboxamide

HRID 2041007Notes

Reaction equation

[CH3:1][N:2]([CH3:15])[C:3]([C:5]1[CH:14]=[CH:13][C:8]2[NH:9][C:10](=S)[O:11][C:7]=2[CH:6]=1)=[O:4].Cl.Cl.[NH:18]1[CH2:22][CH2:21][C@@H:20]([N:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)[CH2:19]1>C1(C)C(C)=CC=CC=1.ClCCl>[CH3:1][N:2]([CH3:15])[C:3]([C:5]1[CH:14]=[CH:13][C:8]2[N:9]=[C:10]([N:18]3[CH2:22][CH2:21][C@@H:20]([N:23]4[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]4)[CH2:19]3)[O:11][C:7]=2[CH:6]=1)=[O:4]

Participants

Conditions

Temperature: 150 °C

Procedure

N,N-Dimethyl-2-thioxo-2,3-dihydrobenzo[d]oxazole-6-carboxamide (Example 92C, 44 mg, 0.119 mmol) and (R)-1-(pyrrolidin-3-yl)piperidine dihydrochloride (Reference Example 5c, 54 mg, 0.238 mmol) were combined in xylene (1 mL) and heated to 150° C. for 30 minutes. The mixture was diluted with dichloromethane, washed with water, and the organic layer was absorbed on silica gel. The crude mixture was purified by silica gel chromatography eluting with a gradient of methanol in dichloromethane (2-20%) to afford the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 1.43-1.53 (m, 2 H) 1.59-1.70 (m, 4 H) 1.91-2.07 (m, 1 H) 2.23-2.35 (m, 1 H) 2.40-2.62 (m, 4 H) 2.93-3.13 (m, 7 H) 3.41-3.51 (m, 1 H) 3.55-3.66 (m, 1 H) 3.80-3.90 (m, 1 H) 3.96 (dd, J=10.00, 7.29 Hz, 1 H) 7.22-7.28 (m, 1 H) 7.30-7.35 (m, 1 H) 7.37-7.40 (m, 1 H); MS (ESI+) m/z 343.0 (M+H)+.

Workup

washwashed with water
customthe organic layer was absorbed on silica gel
customThe crude mixture was purified by silica gel chromatography
washeluting with a gradient of methanol in dichloromethane (2-20%)

Sources & evidence

ORD record: ord-2f234c884cd74ec68c45cc04bed1feca
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08580968B2

Reaction notes

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