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

HRID 1184819Notes

Reaction equation

HRID 1184819 reaction equation
[NH2:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][N:9]=2)[S:4][C:3]=1[C:11]([OH:13])=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.[NH2:48][C:49]1[CH:50]=[C:51]([NH:56][C:57](=[O:69])[C:58]2[CH:63]=[CH:62][CH:61]=[C:60]([C:64]([C:67]#[N:68])([CH3:66])[CH3:65])[CH:59]=2)[CH:52]=[CH:53][C:54]=1[CH3:55]>CN(C=O)C>[NH2:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][N:9]=2)[S:4][C:3]=1[C:11]([NH:48][C:49]1[CH:50]=[C:51]([NH:56][C:57](=[O:69])[C:58]2[CH:63]=[CH:62][CH:61]=[C:60]([C:64]([C:67]#[N:68])([CH3:65])[CH3:66])[CH:59]=2)[CH:52]=[CH:53][C:54]=1[CH3:55])=[O:13]

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 122257127-Aminothieno[2,3-b]pyrazine-6-carboxylic acidHCID 67125541N-(3-amino-4-methylphenyl)-3-(2-cyanopropan-2-yl)benzamide hydrochloride

Product 1

HCID 545893917-amino-N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamideYield 55%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 7-aminothieno[2,3-b]pyrazine-6-carboxylic acid (8) (1.6 g, 8.20 mmol), HATU (3.43 g, 9.02 mmol) and DIPEA (4.06 mL, 24.59 mmol) in DMF (20 mL) was stirred at rt for 20 min. N-(3-amino-4-methylphenyl)-3-(2-cyanopropan-2-yl)benzamide hydrochloride 6 (2.70 g, 8.20 mmol) was added and stirred overnight at 80° C. Quenched in cold citric acid solution and the resulting precipitate was collected and dried to give crude compound 9 (3.55 g). Triturating with acetonitrile, stirred in water at 90° C. for 30 min, filtrated and dried to yield the title compound 7-amino-N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamide 9 (2.12 g, 55.0%). 1H-NMR (400 MHz, DMSO-d6) 1.77 (s, 6H), 2.23 (s, 3H), 7.06 (br s, 2H), 7.27 (d, J=8.6 Hz, 1H), 7.60 (t, J=7.8 Hz, 2H), 7.75 (m, 1H), 7.82 (br s, 1H), 7.95 (d, J=7.8 Hz, 1H), 8.05 (m, 1H), 8.78 (q, J=2.7 and 2.3 Hz, 2H), 9.47 (br s, 1H), 10.32 (br s, 1H). (m/z)=471 (M+H)+.

Workup

  1. customQuenched in cold citric acid solution
  2. customthe resulting precipitate was collected
  3. customdried
  4. customto give crude compound 9 (3.55 g)
  5. customTriturating with acetonitrile
  6. stirringstirred in water at 90° C. for 30 min
  7. filtrationfiltrated
  8. customdried

Sources & evidence

ORD record
ord-2b2c670824ca443a9a5424903495026d
Source dataset
uspto-grants-2014_03
Patent number
US08669256B2

Reaction notes

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