Hydrochloric Acid → 2-acetyl-N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamide

HRID 1184832Notes

Reaction equation

HRID 1184832 reaction equation
Cl[C:2]1[N:3]=[C:4]2[CH:10]=[C:9]([C:11]([NH:13][C:14]3[CH:19]=[C:18]([NH:20][C:21](=[O:33])[C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([C:31]#[N:32])([CH3:30])[CH3:29])[CH:23]=4)[CH:17]=[CH:16][C:15]=3[CH3:34])=[O:12])[S:8][C:5]2=[N:6][CH:7]=1.[CH2:35]([O:37]C([Sn](CCCC)(CCCC)CCCC)=C)[CH3:36].Cl>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:35]([C:2]1[N:3]=[C:4]2[CH:10]=[C:9]([C:11]([NH:13][C:14]3[CH:19]=[C:18]([NH:20][C:21](=[O:33])[C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([C:31]#[N:32])([CH3:30])[CH3:29])[CH:23]=4)[CH:17]=[CH:16][C:15]=3[CH3:34])=[O:12])[S:8][C:5]2=[N:6][CH:7]=1)(=[O:37])[CH3:36]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 547564232-chloro-N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamide

Product 1

HCID 671255852-acetyl-N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamideYield 25.6%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A solution of 2-chloro-N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamide 24 (50 mg, 0.102 mmol), bis(triphenylphosphine)palladium(ii) chloride (7.16 mg, 10.2 μmol) and 1-ethoxyvinyltri-n-butyltin (0.103 mL, 0.306 mmol) toluene (3 mL) was stirred at 100° C. for 2 h. Cooled down to rt, 4N HCl in Dioxane (1 mL) was added and stirred for 1 h. Diluted with EtOAC, filtrated and evaporated. Purification by chromatography (0-10% EtOAc in CH2Cl2) gave the title compound 2-acetyl-N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamide 25g (13 mg, 25.6%). NMR (400 MHz, DMSO-d6) 1.76 (s, 6H), 2.28 (s, 3H), 2.76 (s, 3H), 7.33 (d, J=8.2 Hz, 1H), 7.58-7.68 (m, 2H), 7.76 (d, J=7.8 Hz, 1H), 7.91 (d, J=1.9 Hz, 1H), 7.96 (d, J=7.8 Hz, 1H), 8.06 (s, 1H), 8.65 (s, 1H), 9.20 (s, 1H), 10.39 (s, 1H), 10.57 (s, 1H). (m/z)=498 (M+H)+.

Workup

  1. additionDiluted with EtOAC
  2. filtrationfiltrated
  3. customevaporated
  4. customPurification by chromatography (0-10% EtOAc in CH2Cl2)

Sources & evidence

ORD record
ord-e257b8b2966e4c6b97111fdda57b879d
Source dataset
uspto-grants-2014_03
Patent number
US08669256B2

Reaction notes

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