Sodium Carbonate → N-cyclopropylmethyl-6-[2-methyl-5-(3-pyridin-2-yl-phenylcarbamoyl)-phenyl]-nicotinamide

HRID 1246026노트

반응식

HRID 1246026 반응식
Cl[C:2]1[CH:14]=[CH:13][C:5]([C:6]([NH:8][CH2:9][CH:10]2[CH2:12][CH2:11]2)=[O:7])=[CH:4][N:3]=1.[CH3:15][C:16]1[CH:36]=[CH:35][C:19]([C:20]([NH:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=3)[CH:24]=2)=[O:21])=[CH:18][C:17]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.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>[CH:10]1([CH2:9][NH:8][C:6](=[O:7])[C:5]2[CH:13]=[CH:14][C:2]([C:17]3[CH:18]=[C:19]([C:20](=[O:21])[NH:22][C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=5)[CH:24]=4)[CH:35]=[CH:36][C:16]=3[CH3:15])=[N:3][CH:4]=2)[CH2:12][CH2:11]1

참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 112758456-chloro-N-(cyclopropylmethyl)pyridine-3-carboxamide2회HCID 219145484-methyl-N-(3-pyridin-2-yl-phenyl)-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzamide2회

생성물 1

HCID 21914529N-cyclopropylmethyl-6-[2-methyl-5-(3-pyridin-2-yl-phenylcarbamoyl)-phenyl]-nicotinamide수율 60.1%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 6228Dimethylformamide용매

실험 절차

6-Chloro-N-cyclopropylmethylnicotinamide (Intermediate 1) (18.5 mg, 0.073 mmol) and 4-methyl-N-(3-pyridin-2-yl-phenyl)-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzamide (Intermediate 6) (30 mg, 0.072 mmol), aqueous sodium carbonate (2N, 0.5 ml) and tetrakis(triphenylphosphine)palladium (4 mg) were heated at 90° C. in DMF (1 ml) for 4 hours. The reaction was absorbed onto silica, applied to a bond-elut (5 g, silica) and eluted with an ethylacetate/cyclohexane (0 to 100%) and then acetone. The solvent was evaporated from the product fractions under vacuum and the residue triturated with ether to give N-cyclopropylmethyl-6-[2-methyl-5-(3-pyridin-2-yl-phenylcarbamoyl)-phenyl]-nicotinamide as a white solid (20 mg). LCMS: retention time 3.18 min, MH+ 463. NMR: δH [2H6]-DMSO 10.43,(1H, s), 9.14,(1H, s), 8.86,(1H, t), 8.69,(1H, s), 8.53,(1H, s), 8.34,(1H, d), 8.11,(1H, s), 8.01,(1H, d), 7.95–7.89,(3H, m), 7.81–7.78,(2H, m), 7.53–7.46, (2H, m), 7.38,(1H, t), 3.21,(2H, t), 2.44,(3H, s), 1.07,(1H, m), 0.47,(2H, m), 0.27,(2H, m).

후처리

  1. customThe reaction was absorbed onto silica
  2. washeluted with an ethylacetate/cyclohexane (0 to 100%)
  3. customThe solvent was evaporated from the product fractions under vacuum
  4. customthe residue triturated with ether

출처 및 근거

ORD 기록
ord-c4d32240fb15467ea08825990858d169
출처 데이터셋
uspto-grants-2006_10
특허 번호
US07125898B2

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