Dichloromethane → HCID 178502020, compound

HRID 518767Notes

Reaction equation

HRID 518767 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:4][C:3]=1[NH:15][C@@H:16]1[CH2:21][CH2:20][C@H:19]([C:22]([NH:24][CH:25]([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]1.[CH3:28][O:29][C:30]([NH:32][C:33](=NC(OC)=O)SC)=[O:31].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(Cl)Cl>CO>[CH:25]([NH:24][C:22]([C@@H:19]1[CH2:20][CH2:21][C@H:16]([N:15]2[C:3]3[CH:4]=[C:5]([CH2:8][N:9]4[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]4)[CH:6]=[CH:7][C:2]=3[N:1]=[C:33]2[NH:32][C:30](=[O:31])[O:29][CH3:28])[CH2:17][CH2:18]1)=[O:23])([CH3:27])[CH3:26]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 98708Methyl [[(methoxycarbonyl)amino](methylthio)methylene]carbamateHCID 521998p-Toluenesulfonic acid monohydrateHCID 178457833HCID 178457833, compound

Product 1

HCID 178502020HCID 178502020, compoundYield 65.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of cis-4-(2-amino-5-(piperidin-1-ylmethyl)phenylamino)-N-isopropylcyclohexanecarboxamide (0.300 g, 0.805 mmol) in MeOH (4.5 mL) was added 1,3-bis(methoxycarbonyl)-2-methyl-2-thiopseudourea (0.166 g, 0.805 mmol) and p-toluenesulfonic acid monohydrate (0.168 g, 0.886 mmol). The reaction mixture was heated at 80° C. for 2 hours and then concentrated under vacuum. The residue was dissolved in DCM and was washed with saturated aqueous NaHCO3. The organic layer was dried over sodium sulfate and concentrated under vacuum. The residue was purified by flash chromatography, eluting with 0-100% 90:10:1 DCM/MeOH/NH4OH:DCM to afford methyl 1-(cis-4-(isopropylcarbamoyl)cyclohexyl)-6-(piperidin-1-ylmethyl)-1H-benzo[d]imidazol-2-ylcarbamate (0.239 g, 65.1% yield). MS, m/z (C25H37N5O3); calcd, 455.59. found 456.2 [M+H]. 1H NMR (400 MHz, CDCl3) δ ppm 1.23 (d, J=6.55 Hz, 6H) 1.38-1.49 (m, 2H) 1.52-1.67 (m, 4H) 1.67-1.85 (m, 6H) 2.10-2.20 (m, 2H) 2.34-2.51 (m, 4H) 2.58-2.73 (m, 2H) 3.54-3.66 (m, 1H) 3.79 (s, 3H) 4.20 (dt, J=13.70, 6.70 Hz, 1H) 4.86 (tt, J=12.79, 4.47 Hz, 1H) 5.34 (br. d, J=7.20 Hz, 1H) 7.13-7.25 (m, 2H) 7.61 (br. s., 1H) 11.29 (br. s., 1H).

Workup

  1. concentrationconcentrated under vacuum
  2. dissolutionThe residue was dissolved in DCM
  3. washwas washed with saturated aqueous NaHCO3
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified by flash chromatography
  7. washeluting with 0-100% 90:10:1 DCM/MeOH/NH4OH

Sources & evidence

ORD record
ord-ba70850800be4031b810fae2f16dd6cb
Source dataset
uspto-grants-2015_08
Patent number
US09115127B2

Reaction notes

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