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

HRID 1184857Notes

Reaction equation

HRID 1184857 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.[CH2:28]([N:30]([C:37]1[C:45]2[C:40](=[N:41][CH:42]=[CH:43][N:44]=2)[S:39][C:38]=1[C:46]([O-])=[O:47])C(=O)C(F)(F)F)[CH3:29]>C1(C)C=CC=CC=1.CCOC(C)=O>[C:21]([C:18]([C:14]1[CH:13]=[C:12]([CH:17]=[CH:16][CH:15]=1)[C:11]([NH:10][C:5]1[CH:6]=[CH:7][C:8]([CH3:9])=[C:3]([NH:2][C:46]([C:38]2[S:39][C:40]3=[N:41][CH:42]=[CH:43][N:44]=[C:45]3[C:37]=2[NH:30][CH2:28][CH3:29])=[O:47])[CH:4]=1)=[O:23])([CH3:20])[CH3:19])#[N:22]

Participants

6

Reactant 3

HCID 16682925TrimethylaluminumHCID 67125541N-(3-amino-4-methylphenyl)-3-(2-cyanopropan-2-yl)benzamide hydrochlorideHCID 866801717-(N-ethyl-2,2,2-trifluoroacetamido)thieno[2,3-b]pyrazine-6-carboxylate

Product 1

HCID 54754764N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)-7-(ethylamino)thieno[2,3-b]pyrazine-6-carboxamideYield 5%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of N-(3-amino-4-methylphenyl)-3-(2-cyanopropan-2-yl)benzamide hydrochloride 6 (40 mg, 0.121 mmol) in toluene (1 mL) was added trimethylaluminum (0.243 mL, 0.485 mmol) and stirred for 15 at rt. 7-(N-ethyl-2,2,2-trifluoroacetamido)thieno[2,3-b]pyrazine-6-carboxylate 45 (42.1 mg, 0.121 mmol) in toluene (1 mL) was added and the reaction was stirred overnight at 70° C. Diluted with EtOAc and washed with seignette salt solution. Organic layer was washed with brine, dried and evaporated. Purification by HPLC gave the title compound N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)-7-(ethylamino)thieno[2,3-b]pyrazine-6-carboxamide 46 (3 mg, 4.96%). NMR (400 MHz, DMSO-d6) 1.20 (t, J=7.4 Hz, 3H), 1.75 (s, 6H), 2.22 (s, 1H), 3.98 (q, J=14.0 and 6.5 Hz, 12H), 7.26 (d, J=8.2 Hz, 1H), 7.58-7.64 (m, 2H), 7.75 (d, J=7.8 Hz, 1H), 7.82 (d, J=1.9 Hz, 1H), 7.95 (d, J=7.8 Hz, 1H), 8.04-8.11 (m, 2H), 8.74 (d, J=2.3 Hz, 1H), 8.78 (d, J=2.3 Hz, 1H), 9.53 (s, 1H), 10.32 (s, 1H). (m/z)=499 (M+H)+.

Workup

  1. stirringthe reaction was stirred overnight at 70° C
  2. washwashed with seignette salt solution
  3. washOrganic layer was washed with brine
  4. customdried
  5. customevaporated
  6. customPurification by HPLC

Sources & evidence

ORD record
ord-fbd43ee13604412881f9bb3184c3931c
Source dataset
uspto-grants-2014_03
Patent number
US08669256B2

Reaction notes

Loading…