Trifluoroacetic acid → HCID 131720260, compound

HRID 1490113Notes

Reaction equation

HRID 1490113 reaction equation
[CH2:1]1[CH2:7][CH2:6][CH:5]([C:8]2([NH:21][C:22]([NH:24][C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([CH2:31][NH:32][C:33]4[N:34](C(OC(C)(C)C)=O)[CH:35]=[CH:36][N:37]=4)[CH:26]=3)=[O:23])[N:14]=[CH:13][C:12]3[CH:15]=[CH:16][CH:17]=[CH:18][C:11]=3[N:10]([CH3:19])[C:9]2=[O:20])[CH2:4][CH2:3][CH2:2]1.FC(F)(F)C(O)=O>ClCCl>[CH2:2]1[CH2:3][CH2:4][CH:5]([C:8]2([NH:21][C:22]([NH:24][C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([CH2:31][NH:32][C:33]4[NH:37][CH:36]=[CH:35][N:34]=4)[CH:26]=3)=[O:23])[N:14]=[CH:13][C:12]3[CH:15]=[CH:16][CH:17]=[CH:18][C:11]=3[N:10]([CH3:19])[C:9]2=[O:20])[CH2:6][CH2:7][CH2:1]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57277900HCID 57277900, compound

Product 1

HCID 131720260HCID 131720260, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of N-[3(R,S)-5-cycloheptyl-2,3-dihydro-1-methyl-2-oxo-1H-1,4-benzodiazepin-3-yl]N'-[3-[(1-(tert-butyloxycarbonyl)imidazol-2-ylamino]methyl)phenyl] urea in anhydrous dichloromethane (5 ml) at room temperature, under nitrogen, was added trifluoroacetic acid (0.5 ml). After stirring for 3 h the solvent was evaporated in vacuo and the residue azeotroped with toluene (20 ml). The residue was partitioned between ethyl acetate (20 ml) and water (20 ml). The organic layer was separated, washed with 0.5M sodium carbonate solution (2×20 ml) and water (20 ml), then the organic layer separated and dried (Na2SO4). The solvent was evaporated and the residue chromatographed on silica gel using a gradient elution of dichloromethane:methanol (90:10) followed by methanol to afford the title compound (33 mg) as a white solid. 1H NMR (360 MHz, D6 -DMSO) δ 1.12-1.80 (11H, m), 1.92-1.97 (1H, m), 3.10-3.18 (1H, m), 3.32 (3H, s), 4.25 (2H, d, J=6.2 Hz), 5.04 (1H, d, J=8.4 Hz) 6.42 (1H, m), 6.49 (2H, s), 6.87 (1H, d, J=7.6 Hz), 7.14 (1H, t, J=7.9 Hz), 7.23-7.29 (3H, m), 7.37 (1H, dd, J=7.2 and 7.2 Hz), 7.54 (1H, m), 7.63 (1H, dd, J=7.1 and 7.1 Hz), 7.76 (1H, d, J=6.7 Hz), 8.95 (1H, s). MS (FAB) 500 (M+1).

Workup

  1. customwas evaporated in vacuo
  2. customthe residue azeotroped with toluene (20 ml)
  3. customThe residue was partitioned between ethyl acetate (20 ml) and water (20 ml)
  4. customThe organic layer was separated
  5. washwashed with 0.5M sodium carbonate solution (2×20 ml) and water (20 ml)
  6. customthe organic layer separated
  7. dry with materialdried (Na2SO4)
  8. customThe solvent was evaporated
  9. customthe residue chromatographed on silica gel using
  10. washa gradient elution of dichloromethane:methanol (90:10)

Sources & evidence

ORD record
ord-9c8a3582994b48fc85bf25631a2eb4b3
Source dataset
uspto-grants-1997_10
Patent number
US05681833

Reaction notes

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