Sodium Bicarbonate → Ethyl 1-(1-methylazetidin-3-yl)-4-oxo-6-(6-(3-propylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-1,4-dihydroquinoline-3-carboxylate

HRID 2061820노트

반응식

HRID 2061820 반응식
I[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH:12]1[CH2:15][N:14]([CH3:16])[CH2:13]1)[CH:7]=[C:6]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:5]2=[O:22].[CH2:23]([NH:26][C:27](=[O:47])[NH:28][C:29]1[N:34]=[CH:33][C:32](B(O)O)=[C:31]([C:38]2[S:39][CH:40]=[C:41]([C:43]([F:46])([F:45])[F:44])[N:42]=2)[CH:30]=1)[CH2:24][CH3:25].C(=O)(O)[O-].[Na+]>C(COC)OC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:16][N:14]1[CH2:15][CH:12]([N:8]2[C:9]3[C:4](=[CH:3][C:2]([C:32]4[CH:33]=[N:34][C:29]([NH:28][C:27]([NH:26][CH2:23][CH2:24][CH3:25])=[O:47])=[CH:30][C:31]=4[C:38]4[S:39][CH:40]=[C:41]([C:43]([F:46])([F:44])[F:45])[N:42]=4)=[CH:11][CH:10]=3)[C:5](=[O:22])[C:6]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:7]2)[CH2:13]1

참가 물질

6

반응물 3

HCID 516892Sodium BicarbonateHCID 594160686-(3-Propylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid2회HCID 59416185Ethyl 6-iodo-1-(1-methylazetidin-3-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate2회

생성물 1

HCID 44540347Ethyl 1-(1-methylazetidin-3-yl)-4-oxo-6-(6-(3-propylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-1,4-dihydroquinoline-3-carboxylate

시약·촉매·용매 2

HCID 178418476HCID 178418476, 화합물촉매HCID 80711,2-Dimethoxyethane용매

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온도
30 °C

실험 절차

A suspension of ethyl 6-iodo-1-(1-methylazetidin-3-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate (Intermediate 31, 500 mg, 1.21 mmol) in dimethoxyethane (9.7 mL) in a vial was stirred with heating to obtain solution. The solution was cooled to 30° C. and trans dichlorobis(triphenylphosphine)palladium (II) (111 mg, 0.16 mmol) was added. The mixture was stirred for ˜10 min at room temperature, then 6-(3-propylureido)-4-(4-trifluoromethylthiazol-2-yl)pyridin-3-ylboronic acid (Intermediate 47, 1.3 eq) was added to the mixture followed by an aqueous solution of sodium bicarbonate (252 mg in 2.4 mL of water) and the vial was sealed. The mixture was stirred at 75° C. for 1 h and then cooled to 0° C. The solid that formed was isolated by filtration, washed with a small amount of dimethoxyethane, then methyl tert-butyl ether to give 735 mg of yellow solid, which was used without further purification.

후처리

  1. temperaturewith heating
  2. customto obtain solution
  3. stirringThe mixture was stirred for ˜10 min at room temperature
  4. customthe vial was sealed
  5. stirringThe mixture was stirred at 75° C. for 1 h
  6. temperaturecooled to 0° C
  7. customThe solid that formed
  8. customwas isolated by filtration
  9. washwashed with a small amount of dimethoxyethane

출처 및 근거

ORD 기록
ord-f208483c3ffc41368405248c7419654c
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08283361B2

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