Ammonium Hydroxide → 1-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indole-5-carboxamide

HRID 227418Notes

Reaction equation

HRID 227418 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][C:13]([C:17](O)=[O:18])=[CH:14][CH:15]=3)[C:10]([C:20]([CH:22]3[C:24]([CH3:26])([CH3:25])[C:23]3([CH3:28])[CH3:27])=[O:21])=[CH:9]2)[CH2:3][CH2:2]1.C(N1C=CN=C1)([N:31]1C=CN=C1)=O.[NH4+].[OH-]>CCOC(C)=O.C1COCC1>[O:1]1[CH2:2][CH2:3][CH:4]([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][C:13]([C:17]([NH2:31])=[O:18])=[CH:14][CH:15]=3)[C:10]([C:20]([CH:22]3[C:23]([CH3:27])([CH3:28])[C:24]3([CH3:25])[CH3:26])=[O:21])=[CH:9]2)[CH2:5][CH2:6]1

Participants

6

Reactant 3

HCID 14923Ammonium HydroxideHCID 682631,1'-CarbonyldiimidazoleHCID 67269817HCID 67269817, compound

Product 1

HCID 672702631-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indole-5-carboxamideYield 20%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture 1-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indole-5-carboxylic acid (0.10 g, 0.26 mmol, the minor product of Example 114B), 1,1′-carbonyldimidazole (55 mg, 0.34 mmol) and concentrated aqueous NH4OH (2 mL) in 5 mL of EtOAc and 3 mL of THF was processed as described in Example 93 to provide the title compound (20 mg, 0.052 mmol, 20% yield). 1H NMR (CDCl3, 300 MHz) δ ppm 1.32 (s, 6H), 1.36 (s, 6H), 1.39-1.58 (m, 4H), 1.92 (s, 1H), 2.08-2.23 (m, 1H), 3.34 (dt, J=11.4, 2.5 Hz, 2H), 3.94-4.04 (m, 2H), 4.08 (d, J=7.1 Hz, 2H), 7.41 (d, J=8.5 Hz, 1H), 7.67 (s, 1H), 7.98 (dd, J=8.5, 1.4 Hz, 1H), 8.84 (d, J=1.0 Hz, 1H); MS (DCI/NH3) m/z 383 (M+H)+; Anal. Calculated for C23H30N2O3.0.4H2O: C, 70.89; H, 7.97; N, 7.19. Found: C, 70.77; H, 7.91; N, 7.32.

Sources & evidence

ORD record
ord-86e48337ca414ca68994353e0e6c6bbc
Source dataset
uspto-grants-2009_07
Patent number
US07560481B2

Reaction notes

Loading…