Triethylamine → 6-Amino-N-(5-(4-fluoro-phenoxy)-thiophen-2-ylmethyl)-nicotinamide

HRID 2080214Notes

Reaction equation

HRID 2080214 reaction equation
[F:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][C:7]2[S:11][C:10]([CH2:12][NH2:13])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[NH2:16][C:17]1[CH:25]=[CH:24][C:20]([C:21](O)=[O:22])=[CH:19][N:18]=1.F[P-](F)(F)(F)(F)F.N1([P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C)C=O.C(OCC)(=O)C.O>[NH2:16][C:17]1[CH:25]=[CH:24][C:20]([C:21]([NH:13][CH2:12][C:10]2[S:11][C:7]([O:6][C:5]3[CH:14]=[CH:15][C:2]([F:1])=[CH:3][CH:4]=3)=[CH:8][CH:9]=2)=[O:22])=[CH:19][N:18]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 184966-Aminonicotinic acidHCID 10938826Benzotriazol-1-yltris(dimethylamino)phosphonium hexafluorophosphateHCID 23130478C-(5-(4-fluorophenoxy)thiophen-2-yl)methylamine

Product 1

HCID 231305566-Amino-N-(5-(4-fluoro-phenoxy)-thiophen-2-ylmethyl)-nicotinamideYield 72.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of C-(5-(4-fluorophenoxy)thiophen-2-yl)methylamine described in Preparation Example 28 (500 mg, 2.24 mmol) and 6-aminonicotinic acid (340 mg, 2.46 mmol) in N,N-dimethylformamide (10 mL) were added benzotriazol-1-yl-tris(dimethylamino)phosphonium hexafluorophosphate (1.1 g, 2.46 mmol) and triethylamine (0.6 mL, 4.48 mmol), and the solution was stirred for 30 minutes at 60° C. Water and ethyl acetate were added to the reaction solution, which was then partitioned, and the organic layer was washed with water three times. The organic layer was passed through a glass filter lined with NH silica gel and silica gel (1:1), and eluted with a mixture solvent of ethyl acetate and methanol (20:1). The solvent was evaporated in vacuo, ethyl acetate and hexane were added to the residue, the generated solid was collected by filtration, and the title compound (560 mg, 1.63 mmol, 72.8%) was obtained as a slightly yellow solid.

Workup

  1. customwas then partitioned
  2. washthe organic layer was washed with water three times
  3. filtrationfilter
  4. washeluted with a mixture solvent of ethyl acetate and methanol (20:1)
  5. customThe solvent was evaporated in vacuo, ethyl acetate and hexane
  6. additionwere added to the residue
  7. filtrationthe generated solid was collected by filtration

Sources & evidence

ORD record
ord-6d9ea1d8a1e54960beaaaef8d85f5779
Source dataset
uspto-grants-2011_04
Patent number
US07932272B2

Reaction notes

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