Triethylamine → 2-[1,4'-Bipiperidin]-1'-yl-N-ethyl-5-benzoxazolecarboxamide

HRID 2041013Notes

Reaction equation

HRID 2041013 reaction equation
[N:1]1([CH:7]2[CH2:12][CH2:11][N:10]([C:13]3[O:14][C:15]4[CH:21]=[CH:20][C:19]([C:22](O)=[O:23])=[CH:18][C:16]=4[N:17]=3)[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[CH2:26]([NH2:28])[CH3:27].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)CC)C>O1CCCC1.ClCCl>[N:1]1([CH:7]2[CH2:12][CH2:11][N:10]([C:13]3[O:14][C:15]4[CH:21]=[CH:20][C:19]([C:22]([NH:28][CH2:26][CH3:27])=[O:23])=[CH:18][C:16]=4[N:17]=3)[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 11198Ethylamine hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 669058032-(1,4'-Bipiperidin-1'-yl)benzo[d]oxazole-5-carboxylic acid

Product 1

HCID 669057622-[1,4'-Bipiperidin]-1'-yl-N-ethyl-5-benzoxazolecarboxamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
45 °C

Procedure

2-(1,4′-Bipiperidin-1′-yl)benzo[d]oxazole-5-carboxylic acid (Example 95A, 40 mg, 0.121 mmol), ethanamine hydrochloride (15 mg, 0.182 mmol), and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (55 mg, 0.146 mmol) were combined in tetrahydrofuran (3 mL). Triethylamine (51 μL, 0.364 mmol) was added and the mixture was stirred at 45° C. overnight. The reaction mixture was diluted with dichloromethane, washed with a 1 N aqueous solution of sodium hydroxide, and absorbed on silica gel. The crude mixture was purified with silica gel chromatography eluting with a gradient of methanol in dichloromethane (3-18%) to afford the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 1.25 (t, J=7.29 Hz, 3 H) 1.39-1.51 (m, 2 H) 1.52-1.75 (m, 7 H) 1.96 (d, J=12.89 Hz, 2 H) 2.44-2.61 (m, J=4.75 Hz, 4 H) 3.01-3.15 (m, 2 H) 3.43-3.58 (m, 2 H) 4.29-4.41 (m, 2 H) 6.01 (s, 1 H) 7.21-7.28 (m, 1 H) 7.50 (dd, J=8.31, 1.86 Hz, 1 H) 7.66 (d, J=1.36 Hz, 1 H); MS (ESI+) m/z 357.0 (M+H)+.

Workup

  1. washwashed with a 1 N aqueous solution of sodium hydroxide
  2. customabsorbed on silica gel
  3. customThe crude mixture was purified with silica gel chromatography
  4. washeluting with a gradient of methanol in dichloromethane (3-18%)

Sources & evidence

ORD record
ord-388f24f7503a444a8ad8909910105f91
Source dataset
uspto-grants-2013_11
Patent number
US08580968B2

Reaction notes

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