Hydrochloric Acid → HCID 178520484, compound

HRID 1994143Notes

Reaction equation

HRID 1994143 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:34])[CH2:10][CH2:11][C:12]2[CH:33]=[CH:32][C:15]([O:16][C:17]3[CH:22]=[CH:21][N:20]=[C:19]([C:23]4[NH:24][CH2:25][CH:26]([C:28](OC)=[O:29])[N:27]=4)[CH:18]=3)=[CH:14][CH:13]=2)=[CH:4][C:3]=1[C:35]([F:38])([F:37])[F:36].[BH4-].[Na+].Cl>CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:34])[CH2:10][CH2:11][C:12]2[CH:13]=[CH:14][C:15]([O:16][C:17]3[CH:22]=[CH:21][N:20]=[C:19]([C:23]4[NH:24][CH2:25][CH:26]([CH2:28][OH:29])[N:27]=4)[CH:18]=3)=[CH:32][CH:33]=2)=[CH:4][C:3]=1[C:35]([F:36])([F:37])[F:38]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydride2×HCID 178498782HCID 178498782, compound

Product 1

HCID 178520484HCID 178520484, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of methyl 2-{4-[4-(3-{[4-chloro-3-(trifluoromethyl)phenyl]amino}-3-oxopropyl)phenoxy]pyridin-2-yl}-4,5-dihydro-1H-imidazole-4-carboxylate (107 mg, 0.20 mmol) in MeOH (2 mL), at 0° C., was added sodium borohydride (8.0 mg, 0.22 mmol) portionwise. The reaction mixture was stirred at 0° C. for 45 min, and then warmed to rt and stirred for 18 h. After this time additional sodium borohydride (8.0 mg, 0.22 mmol) was added and the mixture was heated at 60° C. for 18 h. The reaction was then cooled to rt, and 1N HCl was added. The solvents were evaporated and the residue was purified by HPLC (250 mm C18 column) eluting with ACN containing 30% to 100% of 0.1% FA in water (20 min gradient) to give A-243 (6.0 mg, 5.8%). 1H NMR (300 MHz, CD3OD) δ: 8.55 (d, 1H), 8.08 (d, 1H), 7.76-7.72 (m, 1H), 7.61 (d, 1H), 7.53 (d, 1H), 7.41-7.38 (m, 2H), 7.11-7.08 (m, 3H), 4.45-4.35 (m, 1H), 4.06 (t, 1H), 3.90-3.83 (m, 1H), 3.74-3.61 (m, 2H), 3.06 (t, 2H), and 2.73 (t, 2H). LCMS: (FA) ES+ 519.1 (M+1).

Workup

  1. temperaturewarmed to rt
  2. stirringstirred for 18 h
  3. temperaturethe mixture was heated at 60° C. for 18 h
  4. temperatureThe reaction was then cooled to rt
  5. customThe solvents were evaporated
  6. customthe residue was purified by HPLC (250 mm C18 column)
  7. washeluting with ACN containing 30% to 100% of 0.1%
  8. customFA in water (20 min gradient)
  9. customto give A-243 (6.0 mg, 5.8%)

Sources & evidence

ORD record
ord-e080010e1199429783ddab0d26a7e6a8
Source dataset
uspto-grants-2010_01
Patent number
US07652041B2

Reaction notes

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