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

HRID 1184822Notes

Reaction equation

HRID 1184822 reaction equation
[CH3:1][NH:2][C:3]1[C:11]2[C:6](=[N:7][CH:8]=[CH:9][N:10]=2)[S:5][C:4]=1[C:12]([OH:14])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Cl.[NH2:49][C:50]1[CH:51]=[C:52]([NH:57][C:58](=[O:70])[C:59]2[CH:64]=[CH:63][CH:62]=[C:61]([C:65]([C:68]#[N:69])([CH3:67])[CH3:66])[CH:60]=2)[CH:53]=[CH:54][C:55]=1[CH3:56]>CN(C=O)C>[C:68]([C:65]([C:61]1[CH:60]=[C:59]([CH:64]=[CH:63][CH:62]=1)[C:58]([NH:57][C:52]1[CH:53]=[CH:54][C:55]([CH3:56])=[C:50]([NH:49][C:12]([C:4]2[S:5][C:6]3=[N:7][CH:8]=[CH:9][N:10]=[C:11]3[C:3]=2[NH:2][CH3:1])=[O:14])[CH:51]=1)=[O:70])([CH3:67])[CH3:66])#[N:69]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67125541N-(3-amino-4-methylphenyl)-3-(2-cyanopropan-2-yl)benzamide hydrochlorideHCID 671255547-(Methylamino)thieno[2,3-b]pyrazine-6-carboxylic acid

Product 1

HCID 54756310N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)-7-(methylamino)thieno[2,3-b]pyrazine-6-carboxamideYield 55.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

A solution of 7-(methylamino)thieno[2,3-b]pyrazine-6-carboxylic acid 12 (1.6 g, 7.65 mmol), HATU (3.20 g, 8.41 mmol) and DIPEA (3.79 mL, 22.94 mmol) in DMF (20 mL) was stirred at rt for 30 min. N-(3-amino-4-methylphenyl)-3-(2-cyanopropan-2-yl)benzamide hydrochloride 6 (2.52 g, 7.65 mmol) was added and stirred overnight at 75° C. Quenched in ice/water and the resulting precipitate was collected. Purification by chromatography (10-20% EtOAc in CH2Cl2), co-evaporate with acetonitrile (2×), stirred in water at 70° C. for 1 h and filtrated to give the title compound N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)-7-(methylamino)thieno[2,3-b]pyrazine-6-carboxamide 13 (2.06 g, 55.6%). 1H-NMR (400 MHz, DMSO-d6) 1.76 (s, 6H), 2.22 (s, 3H), 3.41 (d, J=5.5 Hz, 3H), 7.26 (d, J=8.6 Hz, 1H), 7.60 (t, J=7.8 Hz, 2H), 7.75 (d, J=7.8 Hz, 1H), 7.82 (d, J=1.9 Hz), 1H), 7.94 (d, J=7.8 Hz, 2H), 8.05 (m, 1H), 8.73 (d, J=2.3 Hz, 1H), 8.77 (d, J=2.3 Hz, 1H), 9.55 (br s, 1H), 10.31 (br s, 1H). (m/z)=485 (M+H)+.

Workup

  1. customQuenched in ice/water
  2. customthe resulting precipitate was collected
  3. customPurification by chromatography (10-20% EtOAc in CH2Cl2)
  4. stirringco-evaporate with acetonitrile (2×), stirred in water at 70° C. for 1 h
  5. filtrationfiltrated

Sources & evidence

ORD record
ord-638d000b0e7e4ee5bf1378d5a2a7cdf8
Source dataset
uspto-grants-2014_03
Patent number
US08669256B2

Reaction notes

Loading…