Dichloromethane → HCID 46932597, compound

HRID 1486780Notes

Reaction equation

HRID 1486780 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([CH2:7][N:8]2[CH2:13][CH2:12][CH:11]([CH2:14][NH:15][C:16]([C:18]3[C:26]4[N:25]=[C:24]([CH:27]([CH3:29])[CH3:28])[NH:23][C:22]=4[CH:21]=[CH:20][CH:19]=3)=[O:17])[CH2:10][CH2:9]2)[CH2:3][CH2:2]1.C(N(CC)C(C)C)(C)C.ClCCl.[Cl:42][C:43]1[CH:51]=[CH:50][CH:49]=[CH:48][C:44]=1[C:45](Cl)=[O:46]>O1CCCC1.CN(C)C=O>[Cl:42][C:43]1[CH:51]=[CH:50][CH:49]=[CH:48][C:44]=1[C:45]([N:1]1[CH2:2][CH2:3][CH:4]([CH2:7][N:8]2[CH2:9][CH2:10][CH:11]([CH2:14][NH:15][C:16]([C:18]3[C:26]4[N:25]=[C:24]([CH:27]([CH3:29])[CH3:28])[NH:23][C:22]=4[CH:21]=[CH:20][CH:19]=3)=[O:17])[CH2:12][CH2:13]2)[CH2:5][CH2:6]1)=[O:46]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 691102-Chlorobenzoyl chlorideHCID 81531DiisopropylethylamineHCID 66810992HCID 66810992, compound

Product 1

HCID 46932597HCID 46932597, compoundYield 62%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 2-isopropyl-1H-benzoimidazole-4-carboxylic acid (1-piperidin-4-ylmethylpiperidin-4-ylmethyl)amide (2.1 g, 5.29 mmol) in tetrahydrofuran (26 mL) at room temperature was added N,N-diisopropylethylamine (2.05 g, 15.87 mmol), dichloromethane (12 mL) and N,N-dimethylformamide (5 mL). To the resulting suspension was slowly added o-chlorobenzoyl chloride (1.02 g, 5.82 mmol), and the reaction mixture was stirred for 0.5 h at room temperature. The solution was concentrated in vacuo, the resulting residue diluted with acetic acid (7.5 mL) and water (0.5 mL), and the product purified by reverse phase preparative HPLC. The purified salt was partitioned between dichloromethane and 1M aqueous sodium hydroxide, the organic layer removed and the aqueous layer re-extracted with dichloromethane, and the combined organic layers washed with brine, dried over sodium sulfate and concentrated in vacuo to give the title compound as a white foam (1.75 g, 3.26 mmol, 62%). (m/z): [M+H]+ calcd for C30H38ClN5O2) 536.28. found 536.3. 1H NMR (300 MHz, DMSO-d6): 0.90 (br m, 2H), 1.24 (d, 6H), 1.45 (br m, 2H), 1.68 (br m, 8H), 1.96 (m, 1H), 2.72 (br m, 5H), 3.08 (m, 2H), (3.20, m, 3H), 4.40 (br m, 1H), 7.14 (t, 1H), 7.28 (m, 2H), 7.39 (m, 1H), 7.49 (dd, 1H), 7.66 (dd, 1H).

Workup

  1. concentrationThe solution was concentrated in vacuo
  2. additionthe resulting residue diluted with acetic acid (7.5 mL) and water (0.5 mL)
  3. customthe product purified by reverse phase preparative HPLC
  4. customThe purified salt was partitioned between dichloromethane and 1M aqueous sodium hydroxide
  5. customthe organic layer removed
  6. extractionthe aqueous layer re-extracted with dichloromethane
  7. washthe combined organic layers washed with brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-afd867b2e1254a289de4ed01c37f1694
Source dataset
uspto-grants-2016_08
Patent number
US09428489B2

Reaction notes

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