Ammonia → HCID 58169909, compound

HRID 384038Notes

Reaction equation

HRID 384038 reaction equation
[F:1][C:2]([F:41])([F:40])[C:3]1[CH:4]=[C:5]([CH2:13][N:14]([CH3:39])[C:15]([N:17]2[CH2:30][CH2:29][C@:20]3([NH:24][C@H:23]([C:25]([O:27]C)=O)[CH2:22][CH2:21]3)[CH2:19][C@@H:18]2[C:31]2[CH:36]=[CH:35][C:34]([F:37])=[CH:33][C:32]=2[CH3:38])=[O:16])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[NH3:42]>>[F:1][C:2]([F:40])([F:41])[C:3]1[CH:4]=[C:5]([CH2:13][N:14]([CH3:39])[C:15]([N:17]2[CH2:30][CH2:29][C@:20]3([NH:24][C@H:23]([C:25]([NH2:42])=[O:27])[CH2:22][CH2:21]3)[CH2:19][C@@H:18]2[C:31]2[CH:36]=[CH:35][C:34]([F:37])=[CH:33][C:32]=2[CH3:38])=[O:16])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

3

Reactant 2

HCID 222AmmoniaHCID 58169890HCID 58169890, compound2×

Product 1

HCID 58169909HCID 58169909, compoundYield 95%

Procedure

In a sealed tube a solution of methyl(2S,5S,7R)-8-{[{[3,5-bis(trifluoromethyl)phenyl]methyl}(methyl)amino]carbonyl}-7-(4-fluoro-2-methylphenyl)-1,8-diazaspiro[4.5]decane-2-carboxylate (Intermediate 23, 80 mg, 0.136 mmol) in 7 M methanolic ammonia (5 ml, 35.0 mmol) was shaken overnight. The solvent was evaporated to dryness and the crude was purified by flash-chromatography (Si cartridge 5 g; from 1:0 to 95:5 DCM/MeOH) to give the title compound (74.4 mg, 0.129 mmol, 95% yield) as a white solid. 1H NMR (500 MHz, DMSO-d6) δ ppm 7.95 (s, 1H) 7.61 (s, 2H) 7.15-7.28 (m, 2H) 6.84-6.97 (m, 2H) 6.78 (t, 1H) 4.63 (d, 1H) 4.34 (d, 1H) 4.08-4.22 (m, 1H) 3.48-3.55 (m, 1H) 3.33-3.42 (m, 1H) 2.93 (s, 3H) 2.76 (t, 1H) 2.65 (br. s., 1H) 2.31 (s, 3H) 2.01-2.16 (m, 1H) 1.38-1.85 (m, 7H); HPLC: Rt=4.91 mins; MS: m/z=575 [M+H]+ and 597 [M+Na]+.

Workup

  1. customThe solvent was evaporated to dryness
  2. customthe crude was purified by flash-chromatography (Si cartridge 5 g; from 1:0 to 95:5 DCM/MeOH)

Sources & evidence

ORD record
ord-0094d024851a4ec98a2b535eb9e6287c
Source dataset
uspto-grants-2013_02
Patent number
US08367692B2

Reaction notes

Loading…