Cesium carbonate → HCID 131732444, compound

HRID 1848743Notes

Reaction equation

HRID 1848743 reaction equation
[Br:1][C:2]1[CH:29]=[C:28]([F:30])[C:5]([CH2:6][N:7]2[C:11]3[CH:12]=[C:13]([OH:16])[CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[C@H:17]2[CH2:22][CH2:21][CH2:20][CH2:19][C@H:18]2[C:23]([O:25][CH2:26][CH3:27])=[O:24])=[C:4]([F:31])[CH:3]=1.Cl[CH2:33][C:34]1[C:39]([F:40])=[CH:38][C:37]([CH3:41])=[CH:36][N:35]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C(#N)C>[Br:1][C:2]1[CH:29]=[C:28]([F:30])[C:5]([CH2:6][N:7]2[C:11]3[CH:12]=[C:13]([O:16][CH2:33][C:34]4[C:39]([F:40])=[CH:38][C:37]([CH3:41])=[CH:36][N:35]=4)[CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[C@H:17]2[CH2:22][CH2:21][CH2:20][CH2:19][C@H:18]2[C:23]([O:25][CH2:26][CH3:27])=[O:24])=[C:4]([F:31])[CH:3]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 72214401HCID 72214401, compoundHCID 131732442HCID 131732442, compound

Product 1

HCID 131732444HCID 131732444, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of racemic cis-ethyl 2-(1-(4-bromo-2,6-difluorobenzyl)-6-hydroxy-1H-benzo[d]imidazol-2-yl)cyclohexanecarboxylate (110 mg, 0.22 mmol), 2-(chloromethyl)-3-fluoro-5-methylpyridine (35 mg, 0.22 mmol) in acetonitrile (5 mL) was added Cs2CO3 (79 mg, 0.24 mmol) and heated at 100° Celsius. After 1 hr the mixture was concentrated to dryness and the residue was purified by FCC to provide racemic cis-ethyl 2-(1-(4-bromo-2,6-difluorobenzyl)-6-((3-fluoro-5-methylpyridin-2-yl)methoxy)-1H-benzo[d]imidazol-2-yl)cyclohexanecarboxylate. To the resulting ethyl ester was added MeOH (2 mL), and NaOH (1 mL, 1 N). The mixture was heated to 110° Celsius. After 1 h the mixture was concentrated to dryness and purified by FCC to provide the title compound and the trans-isomer see Example 124. MS (ESI): mass calcd. for C28H25BrF3N3O3, 587.10; m/z found, 588.2 [M+H]+. 1H NMR (500 MHz, CD3OD) δ 8.22 (5, 1H), 7.52-7.45 (m, 2H), 7.28 (d, J=7.6, 2H), 6.99 (d, J=2.0, 1H), 6.88 (dd, J=8.7, 2.3, 1H), 5.54 (two d, J=16.4, 2H), 5.18 (5, 2H), 3.79 (d, J=4.6, 1H), 2.78-2.63 (m, 1H), 2.40 (s, 3H), 2.36-2.20 (m, 1H), 2.12-1.86 (m, 3H), 1.86-1.67 (m, 2H), 1.51-1.39 (m, 2H).

Workup

  1. concentrationAfter 1 hr the mixture was concentrated to dryness
  2. customthe residue was purified by FCC

Sources & evidence

ORD record
ord-5b2250effdd74176822509f99e01ba02
Source dataset
uspto-grants-2015_02
Patent number
US08952177B2

Reaction notes

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