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

HRID 227420Notes

Reaction equation

HRID 227420 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:29](N1C=CN=C1)([N:31]1C=CN=C1)=O.CN>CCOC(C)=O.C1COCC1>[CH3:29][NH:31][C:17]([C:13]1[CH:12]=[C:11]2[C:16](=[CH:15][CH:14]=1)[N:8]([CH2:7][CH:4]1[CH2:5][CH2:6][O:1][CH2:2][CH2:3]1)[CH:9]=[C:10]2[C:20]([CH:22]1[C:23]([CH3:28])([CH3:27])[C:24]1([CH3:25])[CH3:26])=[O:21])=[O:18]

Participants

6

Reactant 3

HCID 6329MethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 67269817HCID 67269817, compound

Product 1

HCID 67269858N-methyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indole-5-carboxamideYield 14%

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 methylamine (2 M solution in THF, 0.2 mL, 0.4 mmol) in 4 mL of EtOAc and 3 mL of THF was processed as described in Example 93 to provide the title compound (14 mg, 0.035 mmol, 14% yield). 1H NMR (DMSO-d6, 300 MHz) δ ppm 1.27 (s, 12H), 1.30-1.46 (m, 4H), 2.03-2.17 (m, 1H), 2.22 (s, 1H), 2.79 (d, J=4.7 Hz, 3H), 3.22 (dt, J=11.4, 3.1 Hz, 2H), 3.80-3.88 (m, 2H), 4.17 (d, J=7.5 Hz, 2H), 7.63-7.77 (m, 2H), 8.32-8.37 (m, 1H), 8.38 (s, 1H), 8.74 (d, J=1.4 Hz, 1H); MS (DCI/NH3) m/z 397 (M+H)+; Anal. Calculated for C24H32N2O2.0.3H2O: C, 71.72; H, 8.18; N, 6.97. Found: C, 71.96; H, 8.19; N, 6.69.

Sources & evidence

ORD record
ord-328c5bf2ce2a42a197d1326a5484a310
Source dataset
uspto-grants-2009_07
Patent number
US07560481B2

Reaction notes

Loading…