Hydrochloric Acid → HCID 58169872, compound

HRID 384043Notes

Reaction equation

HRID 384043 reaction equation
F[B-](F)(F)F.C[O+](C)C.[F:10][C:11]([F:48])([F:47])[C:12]1[CH:13]=[C:14]([C@H:22]([N:24]([CH3:46])[C:25]([N:27]2[CH2:37][CH2:36][C@:30]3([NH:34][C:33](=O)[CH2:32][CH2:31]3)[CH2:29][C@@H:28]2[C:38]2[CH:43]=[CH:42][C:41]([F:44])=[CH:40][C:39]=2[CH3:45])=[O:26])[CH3:23])[CH:15]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:17]=1.C([BH3-])#N.[Na+].Cl.C([O-])(O)=O.[Na+]>ClCCl.CO>[F:48][C:11]([F:10])([F:47])[C:12]1[CH:13]=[C:14]([C@H:22]([N:24]([CH3:46])[C:25]([N:27]2[CH2:37][CH2:36][C@:30]3([NH:34][CH2:33][CH2:32][CH2:31]3)[CH2:29][C@@H:28]2[C:38]2[CH:43]=[CH:42][C:41]([F:44])=[CH:40][C:39]=2[CH3:45])=[O:26])[CH3:23])[CH:15]=[C:16]([C:18]([F:21])([F:19])[F:20])[CH:17]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 2735153Oxonium, trimethyl-, tetrafluoroborate(1-) (1:1)HCID 5003444Sodium cyanoborohydrideHCID 58169900HCID 58169900, compound2×

Product 1

HCID 58169872HCID 58169872, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of trimethyloxonium tetrafluoroborate (5.39 mg, 0.036 mmol) and (5S,7R)—N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-7-(4-fluoro-2-methylphenyl)-N-methyl-2-oxo-1,8-diazaspiro[4.5]decane-8-carboxamide (Intermediate 42, 17 mg, 0.030 mmol) in Dichloromethane (DCM) (2 ml) was stirred at rt for 3 hrs. The mixture was washed with NaHCO3 saturated solution and the aqueous layer was extracted with DCM. The organic layers were combined, filtered through a phase separator tube and concentrated. The residue was dissolved in Methanol (2 ml) and to this solution, cooled to 0° C., was added Sodium cyanoborohydride (5.73 mg, 0.091 mmol). A solution of 1.25M HCl in MeOH was added maintaining the pH around 3-4 and the reaction was left stirring at rt overnight. To the solution NaHCO3 saturated solution and DCM were added and the aqueous layer was extracted with DCM. Organic layers were combined, filtered through a phase separator tube and concentrated. The crude was purified by SP4 (12M cartridge; eluting from 90%:10% to 50%:50% Cy:EtOAc). Relevant fractions were collected obtaining the title compound (13 mg, 0.024 mmol, 78% yield); 1H NMR (500 MHz, DMSO-d6) δ ppm 8.01 (s, 1H) 7.69 (s, 2H) 7.15-7.21 (m, 1H) 6.94 (dd, 1H) 6.83 (t, 1H) 5.20-5.41 (m, 1H) 4.02-4.27 (m, 1H) 3.35-3.44 (m, 1H) 3.02-3.20 (m, 2H) 2.86 (t, 1H) 2.76 (s, 3H) 2.34 (s, 3 H) 1.59-2.19 (m, 8H) 1.47 (d, 3H); UPLC: Rt=0.68 mins, m/z=546 [M+H]+; HPLC: Rt=5.67 mins.

Workup

  1. washThe mixture was washed with NaHCO3 saturated solution
  2. extractionthe aqueous layer was extracted with DCM
  3. filtrationfiltered through a phase separator tube
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in Methanol (2 ml) and to this solution
  6. temperaturemaintaining the pH around 3-4
  7. waitthe reaction was left
  8. extractionthe aqueous layer was extracted with DCM
  9. filtrationfiltered through a phase separator tube
  10. concentrationconcentrated
  11. customThe crude was purified by SP4 (12M cartridge; eluting from 90%:10% to 50%:50% Cy:EtOAc)
  12. customRelevant fractions were collected

Sources & evidence

ORD record
ord-81f27ebda80b4175b074b02c7e279e55
Source dataset
uspto-grants-2013_02
Patent number
US08367692B2

Reaction notes

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