2-Amino-5-methylpyridine → 2-(Methoxymethyl)-N-(5-methylpyridin-2-yl)-4-[4-(methylsulfonyl)-phenoxy]-1-benzofuran-6-carboxamide

HRID 1643756Notes

Reaction equation

HRID 1643756 reaction equation
[CH3:1][O:2][CH2:3][C:4]1[O:5][C:6]2[CH:12]=[C:11]([C:13](O)=[O:14])[CH:10]=[C:9]([O:16][C:17]3[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:19][CH:18]=3)[C:7]=2[CH:8]=1.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.[NH2:60][C:61]1[CH:66]=[CH:65][C:64]([CH3:67])=[CH:63][N:62]=1>CN(C=O)C>[CH3:1][O:2][CH2:3][C:4]1[O:5][C:6]2[CH:12]=[C:11]([C:13]([NH:60][C:61]3[CH:66]=[CH:65][C:64]([CH3:67])=[CH:63][N:62]=3)=[O:14])[CH:10]=[C:9]([O:16][C:17]3[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:24])=[O:25])=[CH:19][CH:18]=3)[C:7]=2[CH:8]=1

Participants

6

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 667559132-(Methoxymethyl)-4-(4-(methylsulfonyl)phenoxy)benzofuran-6-carboxylic acid

Product 1

HCID 667565212-(Methoxymethyl)-N-(5-methylpyridin-2-yl)-4-[4-(methylsulfonyl)-phenoxy]-1-benzofuran-6-carboxamideYield 55%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-(methoxymethyl)-4-(4-(methylsulfonyl)phenoxy)benzofuran-6-carboxylic acid (130 mg, 0.345 mmol) in DMF (5 mL) was added HATU (263 mg, 0.691 mmol) and DIEA (89.3 mg, 0.691 mmol). After stirring the solution at 0° C. for 15 minutes, 2-amino-5-methyl pyridine (74.7 mg, 0.691 mmol) was added. The solution was warmed gradually to room temperature and stirred for 14 h. The reaction was concentrated under high vacuum, and the product was purified by reverse phase HPLC to give the title compound (88 mg, 55%) as a white solid. 1H NMR (300 MHz, CHLOROFORM-D) δ ppm 2.36 (s, 3 H) 3.07 (s, 3 H) 3.46 (s, 3 H) 4.56 (s, 2 H) 6.59 (s, 1 H) 7.07-7.18 (m, 2 H) 7.53 (d, J=1.32 Hz, 1 H) 7.74 (dd, J=8.67, 1.32 Hz, 1 H) 7.85-7.95 (m, 2 H) 8.00 (s, 1 H) 8.09 (s, 1 H) 8.22 (d, J=8.67 Hz, 1 H) 9.10 (s, 1 H). LCMS m/z 467.20 (M+H)+.

Workup

  1. temperatureThe solution was warmed gradually to room temperature
  2. stirringstirred for 14 h
  3. concentrationThe reaction was concentrated under high vacuum
  4. customthe product was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-676b4eb38d374ae1825357d050d14455
Source dataset
uspto-grants-2012_02
Patent number
US08119624B2

Reaction notes

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