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

HRID 1184852Notes

Reaction equation

HRID 1184852 reaction equation
Cl.[NH2:2][C:3]1[CH:4]=[C:5]([NH:10][C:11](=[O:23])[C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([C:21]#[N:22])([CH3:20])[CH3:19])[CH:13]=2)[CH:6]=[CH:7][C:8]=1[CH3:9].C[Al](C)C.[Br:28][C:29]1[C:33]2=[N:34][CH:35]=[CH:36][N:37]=[C:32]2[S:31][C:30]=1[C:38](OCC)=[O:39]>C1(C)C=CC=CC=1>[Br:28][C:29]1[C:33]2[C:32](=[N:37][CH:36]=[CH:35][N:34]=2)[S:31][C:30]=1[C:38]([NH:2][C:3]1[CH:4]=[C:5]([NH:10][C:11](=[O:23])[C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([C:21]#[N:22])([CH3:20])[CH3:19])[CH:13]=2)[CH:6]=[CH:7][C:8]=1[CH3:9])=[O:39]

Participants

5

Reactant 3

HCID 16682925TrimethylaluminumHCID 67125541N-(3-amino-4-methylphenyl)-3-(2-cyanopropan-2-yl)benzamide hydrochlorideHCID 67125567Ethyl 7-bromothieno[2,3-b]pyrazine-6-carboxylate

Product 1

HCID 671255437-bromo-N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamideYield 72%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

To a solution of N-(3-amino-4-methylphenyl)-3-(2-cyanopropan-2-yl)benzamide hydrochloride 6 (230 mg, 0.697 mmol) in toluene (4 mL) was added trimethylaluminum (1.393 mL, 2.79 mmol). After stirring for 15 min, ethyl 7-bromothieno[3,2-b]pyrazine-6-carboxylate 41 (200 mg, 0.697 mmol) in toluene (4 mL) was added and stirred overnight at 60° C. Quenched with 0.5N NaOH solution and extracted with EtOAc. Organic layer was washed with brine, dried and evaporated. Purification by chromatography (0-10% EtOAc in CH2Cl2) gave the title compound 7-bromo-N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamide 42 (268 mg, 72.0%). NMR (400 MHz, CDCl3) 1.80 (s, 6H), 2.49 (s, 3H), 7.31 (d, J=8.2 Hz, 1H), 7.54 (t, J=7.8 Hz, 1H), 7.74 (m, 1H), 7.80 (d, J=7.8 Hz, 2H), 7.95 (s, 1H), 8.00 (s, 1H), 8.36 (d, J=2.3 Hz, 1H), 8.71 (d, J=2.3 Hz, 1H), 8.84 (d, J=2.3 Hz, 1H), 9.10 (s, 1H). (m/z)=534 and 536 (M+H)+.

Workup

  1. stirringstirred overnight at 60° C
  2. customQuenched with 0.5N NaOH solution
  3. extractionextracted with EtOAc
  4. washOrganic layer was washed with brine
  5. customdried
  6. customevaporated
  7. customPurification by chromatography (0-10% EtOAc in CH2Cl2)

Sources & evidence

ORD record
ord-484ea2b2b2014796a45b58add64bbe04
Source dataset
uspto-grants-2014_03
Patent number
US08669256B2

Reaction notes

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