HCID 67539498, compound → HCID 67539640, compound

HRID 1192374Notes

Reaction equation

HRID 1192374 reaction equation
C(OC(=O)[NH:7][CH2:8][CH2:9][C:10]([C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=1)([F:29])[C:11](=[O:28])[N:12]1[CH2:17][CH2:16][N:15]([C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[N:21]=[CH:20][N:19]=2)[CH2:14][CH2:13]1)(C)(C)C>C(Cl)Cl.Cl.CCOCC>[ClH:36].[ClH:36].[NH2:7][CH2:8][CH2:9][C:10]([C:30]1[CH:31]=[CH:32][C:33]([Cl:36])=[CH:34][CH:35]=1)([F:29])[C:11]([N:12]1[CH2:17][CH2:16][N:15]([C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[N:21]=[CH:20][N:19]=2)[CH2:14][CH2:13]1)=[O:28]

Participants

5

Reactant 1

HCID 67539498HCID 67539498, compound

Product 1

HCID 67539640HCID 67539640, compound

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of [3-(4-chlorophenyl)-3-fluoro-4-oxo-4-(4-quinazolin-4-yl-piperazin-1-yl)-butyl]-carbamic acid tert-butyl ester (226 mg, 0.43 mmol) in DCM (2 mL) and 2.0 M HCl in Et2O (1 mL) was stirred for 12 hours. The mixture was concentrated in vacuo and chromatographed (SiO2) using 10% MeOH/DCM followed by 10% (7N NH3 in MeOH)/DCM as eluent. The purified material was dissolved in MeOH followed by the addition of 2.0N HCl in Et2O, and then concentrated in vacuo. The resulting glass was heated at reflux in isopropyl alcohol and concentrated in vacuo. The resulting solid was suspended in acetonitrile and concentrated in vacuo (repeated twice) to give 4-amino-2-(4-chlorophenyl)-2-fluoro-1-(4-quinazolin-4-yl-piperazin-1-yl)-butan-1-one dihydrochloride as a white powder. 1H NMR (DMSO-d6, 400 MHz) δ 8.86 (s, 1H), 8.18 (m, 4H), 8.01 (m, 2H), 7.69 (m, 1H), 7.58 (d, J=8.4 Hz, 2H), 7.40 (d, J=8.6 Hz, 2H), 4.23 (m, 2H), 4.09 (m, 1H), 3.80 (m, 4H), 3.47 (m, 1H), 2.86 (m, 1H), 2.67 (m, 2H), 2.41 (m, 1H). LCMS (APCI+) m/z 428, 430 [M+H]+.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customchromatographed (SiO2)
  3. dissolutionThe purified material was dissolved in MeOH
  4. additionfollowed by the addition of 2.0N HCl in Et2O
  5. concentrationconcentrated in vacuo
  6. temperatureThe resulting glass was heated
  7. temperatureat reflux in isopropyl alcohol
  8. concentrationconcentrated in vacuo
  9. concentrationconcentrated in vacuo (

Sources & evidence

ORD record
ord-3dd13b3d75ca424282ca327ba015755d
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

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