Acrylonitrile → HCID 59031035, compound

HRID 1442660Notes

Reaction equation

[CH:1]1([N:4]([CH:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)[C:5](=[O:19])[C:6]2[CH:11]=[CH:10][C:9]([C@@:12]([OH:18])([CH3:17])[C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=2)[CH2:3][CH2:2]1.[C:26](#[N:29])[CH:27]=[CH2:28].CCOC(C)=O>C1COCC1>[C:26]([CH2:27][CH2:28][N:23]1[CH2:22][CH2:21][CH:20]([N:4]([CH:1]2[CH2:2][CH2:3]2)[C:5](=[O:19])[C:6]2[CH:11]=[CH:10][C:9]([C@@:12]([OH:18])([CH3:17])[C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=2)[CH2:25][CH2:24]1)#[N:29]

Participants

Conditions

Temperature: 50 °C

Procedure

A solution of (S)-N-cyclopropyl-N-(piperidin-4-yl)-4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)benzamide prepared above in step c in Example 1 (73 mg, 0.20 mmol, 1.0 equiv.) in THF (0.70 mL) was treated with acrylonitrile (55 μL, 0.84 mmol, 4.2 equiv.). After being stirred for 24 h at 50° C., the reaction was diluted (EtOAc) and washed (1×1 N aqueous NaOH, and 1× brine). The organic layer was dried (Na2SO4) and concentrated under reduced pressure. Purification of the residue by flash chromatography (SiO2, 0-10% MeOH/CH2Cl2, gradient elution) gave the title compound as a colorless oil: 1H NMR (CDCl3, 400 MHz) δ 7.58 (d, J=8.2 Hz, 2H), 7.48 (d, J=8.2 Hz, 2H), 4.16-4.09 (m, 1H), 3.02-2.98 (m, 2H), 2.75-2.70 (m, 3H), 2.57-2.54 (m, 3H), 2.26-2.20 (m, 2H), 2.15-2.08 (m, 2H), 1.92-1.87 (m, 2H), 1.78 (s, 3H), 0.58-0.53 (m, 2H), 0.46-0.42 (m, 2H); MS(ESI) 410 [M+H]+.

Workup

washwashed (1×1 N aqueous NaOH, and 1× brine)
dry with materialThe organic layer was dried (Na2SO4)
concentrationconcentrated under reduced pressure
customPurification of the residue
washby flash chromatography (SiO2, 0-10% MeOH/CH2Cl2, gradient elution)

Sources & evidence

ORD record: ord-59001355be514bf5bc4080163f9adcec
Source dataset: uspto-grants-2010_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07659287B2

Reaction notes

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