Ammonia → methyl 1-(oxan-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indole-5-carboxylate

HRID 227417Notes

Reaction equation

HRID 227417 reaction equation
[CH3:1]S(OCC1CCOCC1)(=O)=O.[H-].[Na+].[O:15]1[CH2:20][CH2:19][CH:18]([CH2:21][N:22]2[C:30]3[C:25](=[CH:26][C:27]([C:31]([OH:33])=[O:32])=[CH:28][CH:29]=3)[C:24]([C:34]([CH:36]3[C:38]([CH3:40])([CH3:39])[C:37]3([CH3:42])[CH3:41])=[O:35])=[CH:23]2)[CH2:17][CH2:16]1.N>CN(C=O)C>[O:15]1[CH2:20][CH2:19][CH:18]([CH2:21][N:22]2[C:30]3[C:25](=[CH:26][C:27]([C:31]([O:33][CH3:1])=[O:32])=[CH:28][CH:29]=3)[C:24]([C:34]([CH:36]3[C:38]([CH3:40])([CH3:39])[C:37]3([CH3:42])[CH3:41])=[O:35])=[CH:23]2)[CH2:17][CH2:16]1

Participants

6

Reactant 4

HCID 222AmmoniaHCID 24758Sodium hydrideHCID 15166436Oxan-4-ylmethyl methanesulfonateHCID 67269817HCID 67269817, compound

Product 1

HCID 11516830methyl 1-(oxan-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indole-5-carboxylateYield 44%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The product of Example 114A (1.5 g, 5.1 mmol), the product of Example 18A (10 mmol), and NaH (60% dispersion in mineral oil, 0.61 g, 15 mmol) in 40 mL of DMF were processed as described in Example 1D to provide the title compound (0.89 g, 2.2 mmol, 44% yield) and 1-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indole-5-carboxylic acid as a minor product (0.21 g, 0.55 mmol, 11% yield, MS (DCI/NH3) m/z 384 (M+H)+ for the carboxylic acid). Data for Example 114B (major product): 1H NMR (CDCl3, 300 MHz) δ ppm 1.33 (s, 6H), 1.36 (s, 6H), 1.40-1.58 (m, 4H), 1.95 (s, 1H), 2.06-2.24 (m, 1H), 3.34 (dt, J=11.6, 2.5 Hz, 2H), 3.92 (s, 3H), 3.94-4.01 (m, 2H), 4.06 (d, J=7.1 Hz, 2H), 7.36 (d, J=8.8 Hz, 1H), 7.66 (s, 1H), 8.00 (dd, J=8.5, 1.7 Hz, 1H), 9.12 (dd, J=1.7, 0.7 Hz, 1H); MS (DCI/NH3) m/z 398 (M+H)+; Anal. Calculated for C24H31NO4: C, 72.52; H, 7.86; N, 3.52. Found: C, 72.53; H, 7.90; N, 3.48.

Sources & evidence

ORD record
ord-774cd0136e634649bc5927a062f4e1bf
Source dataset
uspto-grants-2009_07
Patent number
US07560481B2

Reaction notes

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