Acetic Acid → HCID 178457348, compound

HRID 518614Notes

Reaction equation

HRID 518614 reaction equation
[F:1][C:2]1[CH:34]=[CH:33][C:5]([C:6](/[N:8]=[C:9]2\[NH:10][C:11]3[CH:25]=[CH:24][C:23]([CH2:26][N:27]4[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]4)=[CH:22][C:12]=3[N:13]\2[C@H:14]2[CH2:19][CH2:18][C@@H:17]([CH:20]=O)[CH2:16][CH2:15]2)=[O:7])=[CH:4][CH:3]=1.[CH:35]([NH2:38])([CH3:37])[CH3:36].CC(O)=O.C([BH3-])#N.[Na+]>CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:6](/[N:8]=[C:9]2\[NH:10][C:11]3[CH:25]=[CH:24][C:23]([CH2:26][N:27]4[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]4)=[CH:22][C:12]=3[N:13]\2[C@H:14]2[CH2:19][CH2:18][C@@H:17]([CH2:20][NH:38][CH:35]([CH3:37])[CH3:36])[CH2:16][CH2:15]2)=[O:7])=[CH:33][CH:34]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 6363IsopropylamineHCID 5003444Sodium cyanoborohydrideHCID 178520967HCID 178520967, compound

Product 1

HCID 178457348HCID 178457348, compoundYield 12.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of (E)-4-fluoro-N-(1-(cis-4-formylcyclohexyl)-6-(piperidin-1-ylmethyl)-1H-benzo[d]imidazol-2(3H)-ylidene)benzamide (75 mg, 0.162 mmol) in MeOH (3.2 mL) was cooled to 0° C. under nitrogen atmosphere. To this mixture was added isopropylamine (0.208 mL, 2.432 mmol) followed by AcOH (0.056 mL, 0.973 mmol). The resulting mixture was stirred for 15 minutes. Solid sodium cyanoborohydride (15.28 mg, 0.243 mmol) was added in one portion, and the resulting mixture was stirred for 18 hours at RT. The reaction mixture was quenched with water (10 mL), and the aqueous layer was extracted with DCM (30 mL). The organic layer was collected, dried over sodium sulfate, and concentrated to dryness under vacuum. The residue was purified by silica gel chromatography (10-30% of 90/10/1 DCM/MeOH/NH4OH in DCM) to afford (E)-4-fluoro-N-(1-(cis-4-((isopropylamino)methyl)cyclohexyl)-6-(piperidin-1-ylmethyl)-1H-benzo[d]imidazol-2(3H)-ylidene)benzamide (10 mg, 12.20% yield). MS m/z=506.2 [M+H]. Calc'd for C30H40FN5O: 505.3.

Workup

  1. stirringthe resulting mixture was stirred for 18 hours at RT
  2. customThe reaction mixture was quenched with water (10 mL)
  3. extractionthe aqueous layer was extracted with DCM (30 mL)
  4. customThe organic layer was collected
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated to dryness under vacuum
  7. customThe residue was purified by silica gel chromatography (10-30% of 90/10/1 DCM/MeOH/NH4OH in DCM)

Sources & evidence

ORD record
ord-0f81d378d5b242fbbb7be31cb77d4f33
Source dataset
uspto-grants-2015_08
Patent number
US09115127B2

Reaction notes

Loading…