Citric Acid → Tert-butyl 4-methyl-3-(thieno[2,3-b]pyrazine-6-carboxamido)phenylcarbamate

HRID 1184838Notes

Reaction equation

HRID 1184838 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.[C:46]([O:50][C:51](=[O:61])[NH:52][C:53]1[CH:58]=[CH:57][C:56]([CH3:59])=[C:55]([NH2:60])[CH:54]=1)([CH3:49])([CH3:48])[CH3:47].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C>[CH3:59][C:56]1[CH:57]=[CH:58][C:53]([NH:52][C:51](=[O:61])[O:50][C:46]([CH3:47])([CH3:49])[CH3:48])=[CH:54][C:55]=1[NH:60][C:10]([C:8]1[S:7][C:3]2=[N:4][CH:5]=[CH:6][N:1]=[C:2]2[CH:9]=1)=[O:12]

Participants

7

Reactant 5

HCID 311Citric AcidHCID 81531Diisopropylethylamine2×HCID 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 246997865-(Boc-amino)-2-methylaniline

Product 1

HCID 67125544Tert-butyl 4-methyl-3-(thieno[2,3-b]pyrazine-6-carboxamido)phenylcarbamateYield 66.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of thieno[2,3-b]pyrazine-6-carboxylic acid (1.01 g, 5.61 mmol), HATU (1.8 g, 5.61 mmol) and DIPEA (1.953 mL, 11.21 mmol) in DMF (8 mL) was stirred for 15 min. (3-Amino-4-methyl-phenyl)-carbamic acid tert-butyl 27 (1.246 g, 5.61 mmol), DIPEA (1 eq) in DMF (8 mL) were added and stirred overnight at rt. Citric acid solution (3%) was added and extracted with EtOAc. Organic layer was washed with NaHCO3 solution, brine, dried and evaporated. Purification by chromatography (0-20% EtOAc in CH2Cl2) gave tert-butyl 4-methyl-3-(thieno[2,3-b]pyrazine-6-carboxamido)phenylcarbamate 28 (1.43 g, 66.4%). (m/z)=385 (M+H)+.

Workup

  1. additionwere added
  2. extractionextracted with EtOAc
  3. washOrganic layer was washed with NaHCO3 solution, brine
  4. customdried
  5. customevaporated
  6. customPurification by chromatography (0-20% EtOAc in CH2Cl2)

Sources & evidence

ORD record
ord-c6783467ffb24d67982eabb77dea16fe
Source dataset
uspto-grants-2014_03
Patent number
US08669256B2

Reaction notes

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