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

HRID 1184870Notes

Reaction equation

HRID 1184870 reaction equation
[NH2:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([C:11]3[O:12][CH:13]=[CH:14][CH:15]=3)[N:9]=2)[S:4][C:3]=1[C:16]([OH:18])=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.[NH2:53][C:54]1[CH:55]=[C:56]([NH:61][C:62](=[O:74])[C:63]2[CH:68]=[CH:67][CH:66]=[C:65]([C:69]([C:72]#[N:73])([CH3:71])[CH3:70])[CH:64]=2)[CH:57]=[CH:58][C:59]=1[CH3:60]>CN(C=O)C>[NH2:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([C:11]3[O:12][CH:13]=[CH:14][CH:15]=3)[N:9]=2)[S:4][C:3]=1[C:16]([NH:53][C:54]1[CH:55]=[C:56]([NH:61][C:62](=[O:74])[C:63]2[CH:68]=[CH:67][CH:66]=[C:65]([C:69]([C:72]#[N:73])([CH3:70])[CH3:71])[CH:64]=2)[CH:57]=[CH:58][C:59]=1[CH3:60])=[O:18]

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 671256527-Amino-2-(furan-2-yl)thieno[2,3-b]pyrazine-6-carboxylic acid

Product 1

HCID 547547667-amino-N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)-2-(furan-2-yl)thieno[2,3-b]pyrazine-6-carboxamideYield 34.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 7-amino-2-(furan-2-yl)thieno[2,3-b]pyrazine-6-carboxylic acid 59 (66 mg, 0.253 mmol), HATU (106 mg, 0.278 mmol) and DIPEA (0.104 mL, 0.632 mmol) in DMF (2 mL) was stirred at rt for 30 min. N-(3-amino-4-methylphenyl)-3-(2-cyanopropan-2-yl)benzamide hydrochloride 6 (83 mg, 0.253 mmol) was added and stirred overnight at 80° C. Quenched in 2N HCl solution, the resulting precipitate was collected and dried. Purification by HPLC gave the title compound 7-amino-N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)-2-(furan-2-yl)thieno[2,3-b]pyrazine-6-carboxamide 60 (47 mg, 34%). NMR (400 MHz, DMSO-d6) 1.76 (s, 6H), 2.23 (s, 3H), 6.79 (dd, J=1.6 and 3.5 Hz, 1H), 7.01 (s, 2H), 7.27 (d, J=8.2 Hz, 1H), 7.46 (d, J=3.5 Hz, 1H), 7.60 (t, J=7.8 Hz, 2H), 7.75 (m, 1H), 7.82 (d, J=1.9 Hz, 1H), 7.95 (m, 1H), 8.01 (m, 1H), 8.05 (m, 1H), 9.16 (s, 1H), 9.48 (s, 1H), 10.33 (s, 1H). (m/z)=537 (M+H)+.

Workup

  1. customQuenched in 2N HCl solution
  2. customthe resulting precipitate was collected
  3. customdried
  4. customPurification by HPLC

Sources & evidence

ORD record
ord-335542bc6a114c90b986ed09d94005c7
Source dataset
uspto-grants-2014_03
Patent number
US08669256B2

Reaction notes

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