Triethylamine → 6-{[4-(4-Methanesulfonyl-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carbonyl]-amino}-nicotinamide

HRID 1643559Notes

Reaction equation

HRID 1643559 reaction equation
[CH3:1][S:2]([C:5]1[CH:25]=[CH:24][C:8]([O:9][C:10]2[C:15]3[CH2:16][C:17]([CH3:20])([CH3:19])[O:18][C:14]=3[CH:13]=[C:12]([C:21](O)=[O:22])[CH:11]=2)=[CH:7][CH:6]=1)(=[O:4])=[O:3].CC[N:28](CC)CC.N[C:34]1[C:39]([C:40]([NH2:42])=[O:41])=[CH:38][N:37]=[CH:36][CH:35]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH3:1][S:2]([C:5]1[CH:25]=[CH:24][C:8]([O:9][C:10]2[C:15]3[CH2:16][C:17]([CH3:20])([CH3:19])[O:18][C:14]=3[CH:13]=[C:12]([C:21]([NH:28][C:36]3[CH:35]=[CH:34][C:39]([C:40]([NH2:42])=[O:41])=[CH:38][N:37]=3)=[O:22])[CH:11]=2)=[CH:7][CH:6]=1)(=[O:4])=[O:3]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 134980824-Amino-3-pyridinecarboxamideHCID 595604274-(4-Methanesulfonyl-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid

Product 1

HCID 595604646-{[4-(4-Methanesulfonyl-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carbonyl]-amino}-nicotinamideYield 38.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-(4-methanesulfonyl-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (15a) (77 mg, 0.21 mmol) in DMF (3 mL) was added Et3N (90.0 uL, 0.65 mmol), 4-aminonicotinic amide (60.0 mg, 0.44 mmol) and HATU (250 mg, 0.66 mmol). The mixture was stirred at room temperature for 3 hr. The mixture was quenched with H2O (10 mL), extracted with EtOAc (2×10 mL). The organic layers was washed with H2O (2×20 mL), dried over MgSO4 and concentrated. The residue was purified by flash column chromatography eluting with 15-30% EtOAc in hexanes to give colorless oil (39 mg, 38% yield). 1H NMR (400 MHz, CDCl3) δ 8.74 (dd, J=4.42, 1.39 Hz, 1 H) 8.46 (dd, J=8.34, 1.26 Hz, 1 H) 7.96 (d, J=8.84 Hz, 2 H) 7.52 (s, 1 H) 7.42-7.50 (m, 2 H) 7.15 (d, J=8.84 Hz, 2 H) 3.08 (s, 3 H) 2.99 (s, 2 H) 1.54 (s, 6 H); LCMS for C24H23N3O6S m/z 482.00 (M+H)+.

Workup

  1. customThe mixture was quenched with H2O (10 mL)
  2. extractionextracted with EtOAc (2×10 mL)
  3. washThe organic layers was washed with H2O (2×20 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified by flash column chromatography
  7. washeluting with 15-30% EtOAc in hexanes

Sources & evidence

ORD record
ord-404aee285bc9495fa44561db3d35c246
Source dataset
uspto-grants-2012_02
Patent number
US08119624B2

Reaction notes

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