Sodium Carbonate → HCID 178499303, 화합물

HRID 73212노트

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HRID 73212 반응식
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][CH:3]=1.[CH3:11][O:12][C:13]([C:15]1[S:16][C:17](I)=[CH:18][C:19]=1[N:20]([C:28]([C@H:30]1[CH2:35][CH2:34][C@H:33]([CH3:36])[CH2:32][CH2:31]1)=[O:29])[CH:21]1[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]1)=[O:14].C1(C)C=CC=CC=1.CO.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.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>[CH3:11][O:12][C:13]([C:15]1[S:16][C:17]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)=[CH:18][C:19]=1[N:20]([C:28]([C@H:30]1[CH2:31][CH2:32][C@H:33]([CH3:36])[CH2:34][CH2:35]1)=[O:29])[CH:21]1[CH2:22][CH2:23][N:24]([CH3:27])[CH2:25][CH2:26]1)=[O:14]

참가 물질

7

반응물 4

HCID 10340Sodium CarbonateHCID 742994-Chlorophenylboronic acidHCID 21867641Toluene methanolHCID 178499357HCID 178499357, 화합물

생성물 1

HCID 178499303HCID 178499303, 화합물수율 72.3%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 1140Toluene용매

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온도
70 °C

실험 절차

To the mixture of 4-chlorophenylboronic acid (46.9 mg, 0.3 mmol) and 5-iodo-3-[(trans-4-methyl-cyclohexanecarbonyl)-(1-methyl-piperidin-4-yl)-amino]-thiophene-2-carboxylic acid methyl ester (50 mg, 0.099 mmol), from step 5, in 5:1 mixture of toluene/MeOH (2.0 mL) was added a solution of Pd(PPh3)4 (12.0 mg, 0.01 mmol, 10 mol %) in toluene (1.0 mL) followed by aqueous 2M Na2CO3 solution (0.1 mL, 0.2 mmol). The resultant reaction mixture was heated at 70° C. for 16 h, cooled to room temperature, filtered off through MgSO4 and washed with EtOAc. Evaporation of the solvent and purification of the residue over preparative TLC (1 mm, 60 A°) using DCM/CHCl3/MeOH/Et3N (100:90:16:1) as an eluent furnished 5-(4-chloro-phenyl)-3-[(trans-4-methyl-cyclohexanecarbonyl)-(1-methyl-piperidin-4-yl)-amino]-thiophene-2-carboxylic acid methyl ester (35.0 mg, 71.5% yield). NMR 1H (CDCl3, 400 MHz): 7.53 (d, J=8.3, 2H), 7.4 (d, J=8.5, 2H), 7.0 (s, 1H), 4.67-4.58 (m, 1H), 3.84 (s, 3H), 2.82-2.64 (m, 1H), 2.2 (s, 3H), 2.14-1.35 (m), 0.763 (d, J=6.6, 3H), 0.76-0.56 (m, 2H).

후처리

  1. customThe resultant reaction mixture
  2. temperaturecooled to room temperature
  3. filtrationfiltered off through MgSO4
  4. washwashed with EtOAc
  5. customEvaporation of the solvent and purification of the residue over preparative TLC (1 mm, 60 A°)

출처 및 근거

ORD 기록
ord-996b89c1390d4703aa19a13933425eb8
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08829030B2

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