Diisopropylethylamine → Olaparib

HRID 1928533Notes

Reaction equation

[F:1][C:2]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15](=[O:22])[NH:14][N:13]=2)=[CH:7][C:3]=1[C:4]([OH:6])=O.C(N(C(C)C)CC)(C)C.[CH:32]1([C:35]([N:37]2[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]2)=[O:36])[CH2:34][CH2:33]1.CN(C(ON1N=NC2C1=CC=CC=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(#N)C>[CH:32]1([C:35]([N:37]2[CH2:42][CH2:41][N:40]([C:4]([C:3]3[CH:7]=[C:8]([CH:9]=[CH:10][C:2]=3[F:1])[CH2:11][C:12]3[C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[C:15](=[O:22])[NH:14][N:13]=3)=[O:6])[CH2:39][CH2:38]2)=[O:36])[CH2:33][CH2:34]1

Participants

Conditions

Temperature: 18 °C

Procedure

2-Fluoro-5-[(4-oxo-3,4-dihydrophthalazin-1-yl)methyl]benzoic acid (D)(15.23 g, 51.07 mmol) was suspended with stirring under nitrogen in acetonitrile (96 ml). Diisopropylethylamine (19.6 ml, 112.3 mmol) was added followed by 1-cyclopropylcarbonylpiperazine (I)(9.45 g, 61.28 mmol) and acetonitrile (1 ml). The reaction mixture was cooled to 18° C. 0-Benzotriazol-1-yl-tetramethyluronium hexafluorophosphate (25.18 g, 66.39 mmol) was added over 30 minutes and the reaction mixture was stirred for 2 hours at room temperature. The reaction mixture was cooled to 3° C. and maintained at this temperature for 1 hour, before being filtered. The filter cake was washed with cold (3° C.) acetonitrile (20 ml) before being dried in vacuo at up to 40° C. to give the title compound as a pale yellow solid (20.21 g).

Workup

temperatureThe reaction mixture was cooled to 3° C.
temperaturemaintained at this temperature for 1 hour
filtrationbefore being filtered
washThe filter cake was washed with cold (3° C.) acetonitrile (20 ml)
custombefore being dried in vacuo at up to 40° C.

Sources & evidence

ORD record: ord-85f3b1d99d314ff2bab00b50778f54ba
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08183369B2

Reaction notes

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