Ammonia → HCID 58169884, compound

HRID 384032Notes

Reaction equation

HRID 384032 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][CH: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][CH: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 6344DichloromethaneHCID 8857Ethyl AcetateHCID 58169849HCID 58169849, compound2×

Product 1

HCID 58169884HCID 58169884, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

In a sealed tube a solution of Methyl (5R,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 (diastereoisomer 1) (Intermediate 7, 6 mg, 9.94 μmol) in 7N Ammonia in MeOH (5 mL, 35.0 mmol) was stirred at 25° C. for 1 day and then it was left still for 2 days. The solvent was evaporated to dryness and the crude was purified by silica cartridges twice (1st time: from 1:0 to 95:5 DCM/MeOH; 2nd time: EtOAc and then 97.5:2.5 DCM/0.5M NH3 in MeOH) to give the title compound (4.7 mg, 7.99 μmol, 80% yield). 1H NMR (500 MHz, DMSO-d6) δ ppm 7.95-8.03 (m, 1H) 7.63-7.73 (m, 2H) 7.29-7.37 (m, 1H) 7.12-7.20 (m, 1H) 7.00-7.06 (m, 1H) 6.86-6.92 (m, 1H) 6.71-6.79 (m, 1H) 5.27-5.38 (m, 1H) 4.34-4.43 (m, 1H) 3.54-3.64 (m, 1H) 3.16-3.25 (m, 1H) 3.03-3.14 (m, 1H) 2.67-2.84 (m, 3H) 2.30-2.41 (m, 3H) 1.96-2.08 (m, 1H) 1.62-1.80 (m, 2 H) 1.38-1.58 (m, 8H).

Workup

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

Sources & evidence

ORD record
ord-98ec1660bbe34049ac1e78de8e17c84e
Source dataset
uspto-grants-2013_02
Patent number
US08367692B2

Reaction notes

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