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

HRID 1184856Notes

Reaction equation

HRID 1184856 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([NH:9][C:10](=[O:22])[C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([C:20]#[N:21])([CH3:19])[CH3:18])[CH:12]=2)[CH:5]=[CH:6][C:7]=1[CH3:8].C[Al](C)C.[F:27][C:28]([F:47])([F:46])[C:29]([NH:31][C:32]1[C:40]2[C:35](=[N:36][CH:37]=[CH:38][N:39]=2)[S:34][C:33]=1[C:41](OCC)=[O:42])=[O:30]>C1(C)C=CC=CC=1.C([O-])(O)=O.[Na+]>[C:20]([C:17]([C:13]1[CH:12]=[C:11]([CH:16]=[CH:15][CH:14]=1)[C:10]([NH:9][C:4]1[CH:5]=[CH:6][C:7]([CH3:8])=[C:2]([NH:1][C:41]([C:33]2[S:34][C:35]3=[N:36][CH:37]=[CH:38][N:39]=[C:40]3[C:32]=2[NH:31][C:29](=[O:30])[C:28]([F:27])([F:47])[F:46])=[O:42])[CH:3]=1)=[O:22])([CH3:19])[CH3:18])#[N:21]

Participants

6

Reactant 3

HCID 16682925TrimethylaluminumHCID 67125542N-(3-amino-4-methylphenyl)-3-(2-cyanopropan-2-yl)benzamideHCID 86680160Ethyl 7-(2,2,2-trifluoroacetamido)thieno[2,3-b]pyrazine-6-carboxylate

Product 1

HCID 86680170N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)-7-(2,2,2-trifluoroacetamido)thieno[2,3-b]pyrazine-6-carboxamideYield 20.8%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
60 °C

Procedure

A solution of N-(3-amino-4-methylphenyl)-3-(2-cyanopropan-2-yl)benzamide 5 (25 mg, 0.085 mmol) and trimethylaluminum (0.170 mL, 0.341 mmol) in toluene (1 mL) was stirred for 30 min. Ethyl 7-(2,2,2-trifluoroacetamido)thieno[2,3-b]pyrazine-6-carboxylate 10 (27.2 mg, 0.085 mmol) in toluene (1 mL) was added and stirred overnight at 60° C. Poured in NaHCO3 solution and extracted with EtOAc. Organic layer was washed with brine, dried and evaporated. Purification by chromatography (20->80 ethylacetate in CH2Cl2) gave the title compound N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)-7-(2,2,2-trifluoroacetamido)thieno[2,3-b]pyrazine-6-carboxamide 44 (10 mg, 20%). NMR (400 MHz, DMSO-d6) 1.76 (s, 6H), 2.26 (s, 3H), 7.29 (d, J=8.2 Hz, 1H), 7.58-7.66 (m, 2H), 7.76 (d, J=8.2 Hz, 1H), 7.91-7.98 (m, 2H), 8.05 (s, 1H), 8.85 (s, 1H), 8.94 (s, 1H), 10.20 (br s, 1H), 10.38 (s, 1H), 11.80 (br s, 1H). (m/z)=567 (M+H)+.

Workup

  1. extractionextracted with EtOAc
  2. washOrganic layer was washed with brine
  3. customdried
  4. customevaporated
  5. customPurification by chromatography (20->80 ethylacetate in CH2Cl2)

Sources & evidence

ORD record
ord-f45f5b15bc154389938564c44590b616
Source dataset
uspto-grants-2014_03
Patent number
US08669256B2

Reaction notes

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