Citric Acid → N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2,4-difluorophenyl)thieno[2,3-b]pyrazine-6-carboxamide

HRID 1184884Notes

Reaction equation

HRID 1184884 reaction equation
[N:1]1[CH:6]=[CH:5][N:4]=[C:3]2[S:7][C:8]([C:10]([OH:12])=O)=[CH:9][C:2]=12.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.[NH2:46][C:47]1[C:48]([F:68])=[CH:49][C:50]([F:67])=[C:51]([NH:53][C:54](=[O:66])[C:55]2[CH:60]=[CH:59][CH:58]=[C:57]([C:61]([C:64]#[N:65])([CH3:63])[CH3:62])[CH:56]=2)[CH:52]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C>[C:64]([C:61]([C:57]1[CH:56]=[C:55]([CH:60]=[CH:59][CH:58]=1)[C:54]([NH:53][C:51]1[C:50]([F:67])=[CH:49][C:48]([F:68])=[C:47]([NH:46][C:10]([C:8]2[S:7][C:3]3=[N:4][CH:5]=[CH:6][N:1]=[C:2]3[CH:9]=2)=[O:12])[CH:52]=1)=[O:66])([CH3:63])[CH3:62])#[N:65]

Participants

7

Reactant 5

HCID 311Citric AcidHCID 81531DiisopropylethylamineHCID 7164578Thieno[2,3-b]pyrazine-6-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67125648N-(5-amino-2,4-difluorophenyl)-3-(2-cyanopropan-2-yl)benzamide

Product 1

HCID 54754768N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2,4-difluorophenyl)thieno[2,3-b]pyrazine-6-carboxamideYield 20.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of thieno[2,3-b]pyrazine-6-carboxylic acid (57.1 mg, 0.317 mmol), HATU (145 mg, 0.381 mmol) and DIPEA (0.105 mL, 0.634 mmol) in DMF (3 mL) was stirred for 15 min. N-(5-amino-2,4-difluorophenyl)-3-(2-cyanopropan-2-yl)benzamide 73 (100 mg, 0.317 mmol) was added and stirred for 2 h at 80° C. Citric acid solution (3%) was added and the resulting precipitate was collected. Purification by HPLC gave the title compound N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2,4-difluorophenyl)thieno[2,3-b]pyrazine-6-carboxamide 74 (31 mg, 20%). NMR (400 MHz, DMSO-d6) 1.76 (s, 6H), 7.61 (m, 2H), 7.79 (m, 1H), 7.85 (t, J=7.8 Hz, 1H), 7.97 (d, J=7.8 Hz, 1H), 8.10 (t, J=2.0 Hz, 1H), 8.56 (s, 1H), 8.77 (d, J=2.3 Hz, 1H), 8.89 (d, J=2.3 Hz, 1H), 10.35 (s, 1H), 10.80 (br s, 1H). (m/z)=478 (M+H)+.

Workup

  1. stirringstirred for 2 h at 80° C
  2. customthe resulting precipitate was collected
  3. customPurification by HPLC

Sources & evidence

ORD record
ord-1851162181864a8ba6bac6da0c9f7f81
Source dataset
uspto-grants-2014_03
Patent number
US08669256B2

Reaction notes

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