Trifluoroacetic acid → HCID 49833859, compound

HRID 473845Notes

Reaction equation

HRID 473845 reaction equation
Cl[C:2]([N:4]1[CH2:10][C:9]2[CH:11]=[C:12]([C:15]3[CH:16]=[CH:17][C:18]4[N:22]=[CH:21][N:20](C(OC(C)(C)C)=O)[C:19]=4[CH:30]=3)[CH:13]=[CH:14][C:8]=2[O:7][CH2:6][CH2:5]1)=[O:3].[NH:31]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1.F[C:39](F)(F)C(O)=O>ClCCl>[N:31]1([C:2]([N:4]2[CH2:10][C:9]3[CH:11]=[C:12]([C:15]4[CH:16]=[CH:17][C:18]5[N:22]=[C:21]([CH3:39])[NH:20][C:19]=5[CH:30]=4)[CH:13]=[CH:14][C:8]=3[O:7][CH2:6][CH2:5]2)=[O:3])[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 8119AzepaneHCID 86672019HCID 86672019, compound

Product 1

HCID 49833859HCID 49833859, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1,1-dimethylethyl 6-[4-(chlorocarbonyl)-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl]-1H-benzimidazole-1-carboxylate (33 mg, 0.08 mmol), was taken into dichloromethane (1.5 mL) followed by addition of homopiperidine (0.1 mL, 0.89 mmol) and the mixture was allowed to stir for 12 h at room temperature. The mixture was then concentrated and the residue partitioned with ethyl acetate and 10% aqueous citric acid. The organic phase was separated and dried over magnesium sulfate then filtered and concentrated. The residue obtained was taken into trifluoroacetic acid (1 mL) and allowed to stand for 1 h at room temperature. The solution was then concentrated and the residue taken into a minimum of aqueous acetonitrile and purified by preparative reverse phase HPLC. Lyophilization of the combined pure fractions afforded 4-(azepan-1-ylcarbonyl)-7-(2-methyl-1H-benzimidazol-6-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine (18 mg) as an amorphous solid. 1H NMR (400 MHz, d6-DMSO): 7.91 (s, 1H), 7.83 (d, 1H), 7.76 (dd, 1H), 7.64 (d, 1H), 7.55 (dd, 1H), 7.06 (d, 1H), 4.42 (s, 2H), 4.22 (br s, 2H), 3.55 (br s, 2H), 3.29 (tr, 4H), 2.64 (s, 3H), 1.65 (br s, 4H), 1.49 (br s, 4H). MS (EI) for C24H28N4O2: 406 (MH+).

Workup

  1. concentrationThe mixture was then concentrated
  2. customthe residue partitioned with ethyl acetate and 10% aqueous citric acid
  3. customThe organic phase was separated
  4. dry with materialdried over magnesium sulfate
  5. filtrationthen filtered
  6. concentrationconcentrated
  7. customThe residue obtained
  8. waitto stand for 1 h at room temperature
  9. concentrationThe solution was then concentrated
  10. custompurified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-5471e4c547aa4c6ba1839313c64adbb1
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

Loading…