3,5-Dibromo-1-methylpyridin-2(1H)-one → N-(3-(5-Amino-6-methoxypyridin-3-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide

HRID 557536

Reaction equation

HRID 557536 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH2:10])[C:5]([O:8][CH3:9])=[N:6][CH:7]=1.[CH3:11][C:12]1[C:17](B2OC(C)(C)C(C)(C)O2)=[CH:16][CH:15]=[CH:14][C:13]=1[NH:27][C:28]([C:30]1[S:34][C:33]2[CH2:35][CH2:36][CH2:37][CH2:38][C:32]=2[CH:31]=1)=[O:29].BrC1C(=O)N(C)C=C(Br)C=1>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:10][C:4]1[CH:3]=[C:2]([C:17]2[C:12]([CH3:11])=[C:13]([NH:27][C:28]([C:30]3[S:34][C:33]4[CH2:35][CH2:36][CH2:37][CH2:38][C:32]=4[CH:31]=3)=[O:29])[CH:14]=[CH:15][CH:16]=2)[CH:7]=[N:6][C:5]=1[O:8][CH3:9]

Participants

6

Reactant 3

HCID 36143503,5-Dibromo-1-methylpyridin-2(1H)-oneHCID 447548695-Bromo-2-methoxypyridin-3-amineHCID 58729134N-(2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide

Product 1

HCID 59740583N-(3-(5-Amino-6-methoxypyridin-3-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamideYield 65%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
95 °C

Procedure

In a 48 mL sealed tube equipped with a magnetic stirring bar was placed 5-bromo-2-methoxypyridin-3-amine (16) (1.0 g, 4.0 mmol), N-(2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide (1(2.4 g, 6.7 mmol), and Pd(PPh3)4 (0.30 g, 0.20 mmol) in DME/1N Na2CO3 (10 mL, 1/1). After the reaction mixture was degassed for 15 min., it was heated at 95° C. for 16 h. Then, the mixture was cooled to room temperature and diluted with dichloromethane (10 mL) and H2O (10 mL), and the layers were separated. The aqueous phase was extracted with dichloromethane (3×10 mL), and the combined organic extracts were washed with H2O (5 mL) and brine (5 mL), dried (Na2SO4), and concentrated. The crude mixture was purified by column chromatography, gradient 0-25% MeOH in dichloromethane, to afford 1.0 g (65%) of N-(3-(5-amino-6-methoxypyridin-3-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide (17) as a solid.

Workup

  1. customIn a 48 mL sealed tube
  2. customequipped with a magnetic stirring bar
  3. customAfter the reaction mixture was degassed for 15 min.
  4. temperatureThen, the mixture was cooled to room temperature
  5. additiondiluted with dichloromethane (10 mL) and H2O (10 mL)
  6. customthe layers were separated
  7. extractionThe aqueous phase was extracted with dichloromethane (3×10 mL)
  8. washthe combined organic extracts were washed with H2O (5 mL) and brine (5 mL)
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated
  11. customThe crude mixture was purified by column chromatography, gradient 0-25% MeOH in dichloromethane

Sources & evidence

ORD record
ord-437d079a894d4149bc5f5440032eea06
Source dataset
uspto-grants-2011_11
Patent number
US08058446B2

Linked notes

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