Ammonia → HCID 58169897, compound

HRID 472705Notes

Reaction equation

HRID 472705 reaction equation
[F:1][C:2]([F:42])([F:41])[C:3]1[CH:4]=[C:5]([C@H:13]([N:15]([CH3:40])[C:16]([N:18]2[CH2:31][CH2:30][C@:21]3([NH:25][C@H:24]([C:26]([O:28]C)=O)[CH2:23][CH2:22]3)[CH2:20][C@@H:19]2[C:32]2[CH:37]=[CH:36][C:35]([F:38])=[CH:34][C:33]=2[CH3:39])=[O:17])[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.CCOC(C)=O.C(Cl)Cl.[NH3:52]>CO>[F:10][C:9]([F:12])([F:11])[C:7]1[CH:6]=[C:5]([C@H:13]([N:15]([CH3:40])[C:16]([N:18]2[CH2:31][CH2:30][C@:21]3([NH:25][C@H:24]([C:26]([NH2:52])=[O:28])[CH2:23][CH2:22]3)[CH2:20][C@@H:19]2[C:32]2[CH:37]=[CH:36][C:35]([F:38])=[CH:34][C:33]=2[CH3:39])=[O:17])[CH3:14])[CH:4]=[C:3]([C:2]([F:1])([F:41])[F:42])[CH:8]=1

Participants

6

Reactant 4

HCID 222AmmoniaHCID 6344Dichloromethane2×HCID 8857Ethyl AcetateHCID 58169846HCID 58169846, compound2×

Product 1

HCID 58169897HCID 58169897, compoundYield 96%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent3×

Procedure

In a sealed tube a solution of Methyl (2S,5S,7R)-8-{[{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}(methyl)amino]carbonyl}-7-(4-fluoro-2-methylphenyl)-1,8-diazaspiro[4.5]decane-2-carboxylate (Intermediate 13, 24.1 mg, 0.04 mmol) in 7N Ammonia in MeOH (5 mL, 35.0 mmol) was stirred at 25° C. for 1 day. The solvent was evaporated to dryness and the crude was purified twice by silica cartridges (2 g) (1st time: with EtOAc and then 97.5:2.5 DCM/0.5 M NH3 in MeOH and 2nd time: from 98.75:1.25 to 95:5 DCM/0.5 M NH3 in MeOH) to give the title compound (22.5 mg, 0.038 mmol, 96% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.92-8.05 (m, 1H) 7.61-7.77 (m, 2H) 7.21-7.27 (m, 1H) 7.13-7.19 (m, 1H) 6.87-6.97 (m, 2H) 6.73-6.83 (m, 1H) 5.25-5.37 (m, 1H) 4.08-4.20 (m, 1H) 3.44-3.55 (m, 1H) 3.26-3.38 (m, 1H) 2.57-2.85 (m, 4H) 2.26-2.36 (m, 3H) 1.98-2.16 (m, 1H) 1.41-1.82 (m, 10H).

Workup

  1. customThe solvent was evaporated to dryness
  2. customthe crude was purified twice by silica cartridges (2 g) (1st time

Sources & evidence

ORD record
ord-179edcc70f244b579837bc630656d602
Source dataset
uspto-grants-2014_01
Patent number
US08633214B2

Reaction notes

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