Citric Acid → HCID 178510428, compound

HRID 930171Notes

Reaction equation

HRID 930171 reaction equation
C[O:2][C:3](=O)[CH:4]([C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]([C:18]2[NH:19][CH:20]=[C:21]([C:23]#[N:24])[N:22]=2)=[O:17])=[C:11]([C:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH:26]=2)[CH:10]=1)[C:5](OC)=[O:6].[BH4-].[Na+].CO.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(O)(C)(C)C.CCOC(C)=O>[C:25]1([C:11]2[CH:10]=[C:9]([CH:4]([CH2:3][OH:2])[CH2:5][OH:6])[CH:14]=[CH:13][C:12]=2[NH:15][C:16]([C:18]2[NH:19][CH:20]=[C:21]([C:23]#[N:24])[N:22]=2)=[O:17])[CH2:30][CH2:29][CH2:28][CH2:27][CH:26]=1

Participants

7

Reactant 4

HCID 311Citric AcidHCID 887MethanolHCID 4311764Sodium borohydrideHCID 178500964HCID 178500964, compound

Product 1

HCID 178510428HCID 178510428, compoundYield 61%

Reagents, catalysts & solvents 2

HCID 6386tert-ButanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 2-{4-[(4-cyano-1H-imidazole-2-carbonyl)-amino]-3-cyclohex-1-enyl-phenyl}-malonic acid dimethyl ester (as prepared in the previous step, 30.0 mg, 0.0710 mmol) and NaBH4 (13.4 mg, 0.355 mmol) in 1 mL of tert-butyl alcohol (t-BuOH) at 80° C. was added MeOH (50 μL) over 5 min. The resulting mixture was stirred at 80° C. for 16 h under Ar. After cooling to RT, the mixture was treated with 10% aq citric acid to a pH of 7. The mixture was then treated with 30 mL of EtOAc, washed with H2O (5 mL) and brine (10 mL). The organic layer was dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography on silica gel with 1-5% MeOH-DCM to afford 14.1 mg (61%) of the title compound as a white solid: 1H-NMR (CD3OD; 400 MHz): δ 8.00 (s, 1H), 7.54 (dd, 1H, J=8.2, 2.3 Hz), 7.46 (d, 1H, J=2.3 Hz), 7.27 (d, 1H, J=8.2 Hz), 5.59 (m, 1H), 3.71-3.84 (m, 4H), 3.29 (m, 1H), 2.15-2.29 (m, 4H), 1.67-1.84 (m, 4H). Mass spectrum (ESI, m/z): Calcd. for C20H22N4O3, 367.2 (M+H). found 366.8.

Workup

  1. temperatureAfter cooling to RT
  2. washwashed with H2O (5 mL) and brine (10 mL)
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash chromatography on silica gel with 1-5% MeOH-DCM

Sources & evidence

ORD record
ord-7064d0eebf424444918a626581f5b6d2
Source dataset
uspto-grants-2016_03
Patent number
US09296726B2

Reaction notes

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