2-Amino-5-methylpyridine → 4-{4-[(Dimethylamino)carbonyl]phenoxy}-2-ethyl-N-(5-methylpyridin-2-yl)-1-benzofuran-6-carboxamide

HRID 1177266Notes

Reaction equation

HRID 1177266 reaction equation
[CH3:1][N:2]([CH3:26])[C:3]([C:5]1[CH:25]=[CH:24][C:8]([O:9][C:10]2[C:15]3[CH:16]=[C:17]([CH2:19][CH3:20])[O:18][C:14]=3[CH:13]=[C:12]([C:21](O)=[O:22])[CH:11]=2)=[CH:7][CH:6]=1)=[O:4].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.[CH3:60][C:61]1[CH:62]=[CH:63][C:64]([NH2:67])=[N:65][CH:66]=1>CN(C=O)C.O>[CH3:1][N:2]([CH3:26])[C:3]([C:5]1[CH:6]=[CH:7][C:8]([O:9][C:10]2[C:15]3[CH:16]=[C:17]([CH2:19][CH3:20])[O:18][C:14]=3[CH:13]=[C:12]([C:21]([NH:67][C:64]3[CH:63]=[CH:62][C:61]([CH3:60])=[CH:66][N:65]=3)=[O:22])[CH:11]=2)=[CH:24][CH:25]=1)=[O:4]

Participants

7

Reactant 4

HCID 153482-Amino-5-methylpyridineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 595601564-{4-[(Dimethylamino)carbonyl]phenoxy}-2-ethyl-1-benzofuran-6-carboxylic acid

Product 1

HCID 595601984-{4-[(Dimethylamino)carbonyl]phenoxy}-2-ethyl-N-(5-methylpyridin-2-yl)-1-benzofuran-6-carboxamideYield 27%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 4-{4-[(dimethylamino)carbonyl]phenoxy}-2-ethyl-1-benzofuran-6-carboxylic acid (400 mg, 1.13 mmol), HATU (671 mg, 1.70 mmol) and DIPEA (226 mg, 1.70 mmol) in DMF (20 mL) was stirred for 1 h. Then 5-methylpyridin-2-amine (146 mg, 2.26 mmol) was added. The resulting solution was stirred overnight. The reaction was monitored by TLC (petroleum ether/EtOAc 1:1). The mixture was poured into water (30 mL) and extracted with EtOAc (30 mL×3). The organic layer was washed with brine (20 mL×2), dried over Na2SO4 and concentrated. The product was purified via preparative HPLC to afford the desired compound (133.7 mg, 27%) as a yellow solid. 1H NMR (400 MHz, CDCl3): δ 8.92 (bs, 1H), 8.25 (d, 1H), 8.03 (s, 1H), 7.82 (s, 1H), 7.55 (d, 2H), 7.44-7.37 (m, 3H), 6.96 (d, 2H), 6.22 (s, 1H), 3.10-2.93 (d, 6H), 2.74 (q, 2H), 2.26 (s, 3H), 1.26 (t, 3H). LCMS m/z 444.40 (M+H)+.

Workup

  1. extractionextracted with EtOAc (30 mL×3)
  2. washThe organic layer was washed with brine (20 mL×2)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe product was purified via preparative HPLC

Sources & evidence

ORD record
ord-978f34284d6846d496c56b4c4af65e18
Source dataset
uspto-grants-2010_11
Patent number
US07842713B2

Reaction notes

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