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

HRID 1184915Notes

Reaction equation

HRID 1184915 reaction equation
[CH2:1]([O:3][C:4]1[N:9]=[C:8]2[S:10][C:11]([C:13]([OH:15])=O)=[CH:12][C:7]2=[N:6][CH:5]=1)[CH3:2].C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[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:13]([C:11]2[S:10][C:8]3=[N:9][C:4]([O:3][CH2:1][CH3:2])=[CH:5][N:6]=[C:7]3[CH:12]=2)=[O:15])[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 67125542N-(3-amino-4-methylphenyl)-3-(2-cyanopropan-2-yl)benzamideHCID 671256133-Ethoxythieno[2,3-b]pyrazine-6-carboxylic acid

Product 1

HCID 67125668N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)-3-ethoxythieno[2,3-b]pyrazine-6-carboxamideYield 7.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 97 (0.085 mmol, 18.29 mg), N,N-diisopropylethylamine (0.426 mmol, 0.070 ml, 55.1 mg) and HATU (0.128 mmol, 48.6 mg) in DMF (1 mL) was stirred for 5 min. N-(3-amino-4-methylphenyl)-3-(2-cyanopropan-2-yl)benzamide 5 (0.085 mmol, 25 mg) was added and stirred at 80° C. over the weekend. The reaction mixture was quenched in citric acid solution and extracted with ethyl acetate (2×). Organic layer was washed with brine, dried and concentrated under reduced pressure. The crude compound was purified with HPLC to give the title compound N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)-3-ethoxythieno[2,3-b]pyrazine-6-carboxamide 98 (3 mg, 7%). NMR (400 MHz, CDCl3) 1.48 (t, 3H), 1.78 (s, 6H), 2.36 (s, 3H), 4.51 (q, J=7.0 Hz, 2H), 7.24 (m, 1H), 7.52 (t, J=7.8 Hz, 1H), 7.72 (t, J=7.8 Hz, 2H), 7.79 (m, 2H), 7.91 (s, 1H), 7.98 (m, 2H), 8.16 (d, J=2 Hz, 1H), 8.32 (s, 1H). (m/z)=501 (M+H)+.

Workup

  1. customThe reaction mixture was quenched in citric acid solution
  2. extractionextracted with ethyl acetate (2×)
  3. washOrganic layer was washed with brine
  4. customdried
  5. concentrationconcentrated under reduced pressure
  6. customThe crude compound was purified with HPLC

Sources & evidence

ORD record
ord-8d00843c95a146018613d04d8c847cc0
Source dataset
uspto-grants-2014_03
Patent number
US08669256B2

Reaction notes

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