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

반응식

HRID 557536 반응식
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]

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 80711,2-Dimethoxyethane용매

반응 조건

온도
95 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-437d079a894d4149bc5f5440032eea06
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08058446B2

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