Water → N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)-7-methylthieno[2,3-b]pyrazine-6-carboxamide

HRID 1184853Notes

Reaction equation

Br[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][N:9]=2)[S:4][C:3]=1[C:11]([NH:13][C:14]1[CH:19]=[C:18]([NH:20][C:21](=[O:33])[C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([C:31]#[N:32])([CH3:30])[CH3:29])[CH:23]=2)[CH:17]=[CH:16][C:15]=1[CH3:34])=[O:12].Cl[CH2:36]Cl.[Cl-].C[Zn+].O>C1COCC1.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[C:31]([C:28]([C:24]1[CH:23]=[C:22]([CH:27]=[CH:26][CH:25]=1)[C:21]([NH:20][C:18]1[CH:17]=[CH:16][C:15]([CH3:34])=[C:14]([NH:13][C:11]([C:3]2[S:4][C:5]3=[N:6][CH:7]=[CH:8][N:9]=[C:10]3[C:2]=2[CH3:36])=[O:12])[CH:19]=1)=[O:33])([CH3:30])[CH3:29])#[N:32]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 7-bromo-N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamide 42 (20 mg, 0.037 mmol) and 1,1′-bis(diphenylphosphino) ferrocene palladium (ii) chloride, complex with dichloromethane (1.513 mg, 1.871 μmol) in THF (1 mL) was added methylzinc chloride (0.037 mL, 0.075 mmol). The reaction was stirred at 60° C. for 2 h. Water was added and the resulting precipitate was collected. Purification by chromatography (20% EtOAc in CH2Cl2) gave the title compound N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)-7-methylthieno[2,3-b]pyrazine-6-carboxamide 43a (4 mg, 22%) NMR (400 MHz, CDCl3) 2.38 (s, 3H), 2.89 (s, 3H), 7.29 (m, 1H), 7.55 (m, 1H), 7.70-7.83 (m, 4H), 7.91 (s, 1H), 7.99 (m, 1H), 8.26 (d, J=1.9 Hz, 1H), 8.64 (d, J=2.3 Hz, 1H), 8.76 (d, J=2.3 Hz, 1H). (m/z)=470 (M+H)+.

Workup

customthe resulting precipitate was collected
customPurification by chromatography (20% EtOAc in CH2Cl2)

Sources & evidence

ORD record: ord-0dd2256fa3a6468aa579dab57e09969f
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08669256B2

Reaction notes

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