Diisopropylethylamine → HCID 67539498, compound

HRID 1192373Notes

Reaction equation

HRID 1192373 reaction equation
C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[C:25]([O:29][C:30]([NH:32][CH2:33][CH2:34][C:35]([C:40]1[CH:45]=[CH:44][C:43]([Cl:46])=[CH:42][CH:41]=1)([F:39])[C:36]([OH:38])=O)=[O:31])([CH3:28])([CH3:27])[CH3:26].Cl.Cl.[N:49]1([C:55]2[C:64]3[C:59](=[CH:60][CH:61]=[CH:62][CH:63]=3)[N:58]=[CH:57][N:56]=2)[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]1.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:25]([O:29][C:30](=[O:31])[NH:32][CH2:33][CH2:34][C:35]([C:40]1[CH:45]=[CH:44][C:43]([Cl:46])=[CH:42][CH:41]=1)([F:39])[C:36](=[O:38])[N:52]1[CH2:53][CH2:54][N:49]([C:55]2[C:64]3[C:59](=[CH:60][CH:61]=[CH:62][CH:63]=3)[N:58]=[CH:57][N:56]=2)[CH2:50][CH2:51]1)([CH3:26])([CH3:27])[CH3:28]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 66570482HCID 66570482, compoundHCID 67538829HCID 67538829, compound

Product 1

HCID 67539498HCID 67539498, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

PyBrop (562 mg, 1.21 mmol) was added in a single portion to a solution of 4-tert-butoxycarbonylamino-2-(4-chlorophenyl)-2-fluoro-butyric acid (400 mg, 1.21 mmol) and 4-piperazin-1-yl-quinazoline dihydrochloride (346 mg, 1.21 mmol) in DCM (12 mL) cooled in an ice bath. DIEA (0.84 mL, 4.82 mmol) was added and the mixture was allowed to warm to ambient temperature and stirred for 12 hours. The mixture was diluted with DCM and washed with 0.1N HCl. The separated DCM layer was dried (Na2SO4), filtered, and concentrated in vacuo. The crude material was chromatographed (SiO2) using 2% MeOH/DCM followed by 5% MeOH/DCM as eluent to give [3-(4-chlorophenyl)-3-fluoro-4-oxo-4-(4-quinazolin-4-yl-piperazin-1-yl)-butyl]-carbamic acid tert-butyl ester (230 mg). LCMS (APCI+) m/z 528, 530 [M+H]+.

Workup

  1. temperaturecooled in an ice bath
  2. washwashed with 0.1N HCl
  3. dry with materialThe separated DCM layer was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was chromatographed (SiO2)

Sources & evidence

ORD record
ord-4e886bc8c7cb4389839087be8b6265b6
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

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