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

反応式

HRID 557536 の反応式
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]

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
95 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-437d079a894d4149bc5f5440032eea06
出典データセット
uspto-grants-2011_11
特許番号
US08058446B2

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