Acetic Acid → HCID 178509609, compound

HRID 526513Notes

Reaction equation

[CH2:1]([NH:8][C:9](=[O:18])[C:10]1[CH:15]=[CH:14][C:13]([NH:16][NH2:17])=[N:12][CH:11]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:19]([C:21]1[CH:26]=[CH:25][C:24]([C:27](=[CH:32]N(C)C)[C:28](OC)=[O:29])=[CH:23][C:22]=1[F:36])#[N:20].C(O)(=O)C.CCN(C(C)C)C(C)C>CC(O)C.CS(C)=O>[CH2:1]([NH:8][C:9](=[O:18])[C:10]1[CH:15]=[CH:14][C:13]([N:16]2[C:28]([OH:29])=[C:27]([C:24]3[CH:25]=[CH:26][C:21]([C:19]#[N:20])=[C:22]([F:36])[CH:23]=3)[CH:32]=[N:17]2)=[N:12][CH:11]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 50 °C

Procedure

Combined N-benzyl-6-hydrazinylnicotinamide (30 mg, 0.124 mmol), methyl 2-(4-cyano-3-fluorophenyl)-3-(dimethylamino)acrylate (40.0 mg, 0.161 mmol) and acetic acid (0.021 mL, 0.371 mmol) in 2-propanol (1.0 mL) and stirred at 20° C. for 28 h. Then Hunig's base (0.130 mL, 0.743 mmol) was added and the reaction mixture was heated at 50° C. for 15 h. The reaction mixture was diluted with DMSO (0.1 mL) and purified by prep HPLC to give the title compound (22 mg, 43.0% yield) as a peach solid. 1H NMR (400 MHz, DMSO-d6) 6 ppm 4.53 (d, J=5.8 Hz, 2H) 7.21-7.30 (m, 1H) 7.31-7.39 (m, 4H) 7.85 (t, J=7.7 Hz, 1H) 7.99 (d, J=8.3 Hz, 1H) 8.10 (d, J=11.9 Hz, 1H) 8.42-8.58 (m, 2H) 8.74 (br. s., 1H) 8.97 (d, J=1.5 Hz, 1H) 9.27 (t, J=5.9 Hz, 1H) 13.81 (br. s., 1H). MS m/z 414 [M+H]+.

Workup

custompurified by prep HPLC

Sources & evidence

ORD record: ord-e5a78b6a945e4cb4b7d672e6907c05f5
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09345713B2

Reaction notes

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