Sodium Carbonate → HCID 68737513、化合物

HRID 869953ノート

反応式

HRID 869953 の反応式
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]([C:11]2([C:14]3[CH:24]=[CH:23][C:17]4[O:18][C:19]([F:22])([F:21])[O:20][C:16]=4[CH:15]=3)[CH2:13][CH2:12]2)=[O:10])[CH:5]=[C:4]([CH3:25])[CH:3]=1.[CH3:26][O:27][C:28]1[C:33](B(O)O)=[CH:32][C:31]([CH3:37])=[CH:30][N:29]=1.C([O-])([O-])=O.[Na+].[Na+]>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>[F:21][C:19]1([F:22])[O:18][C:17]2[CH:23]=[CH:24][C:14]([C:11]3([C:9]([NH:8][C:6]4[N:7]=[C:2]([C:33]5[C:28]([O:27][CH3:26])=[N:29][CH:30]=[C:31]([CH3:37])[CH:32]=5)[CH:3]=[C:4]([CH3:25])[CH:5]=4)=[O:10])[CH2:13][CH2:12]3)=[CH:15][C:16]=2[O:20]1

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 27631282-Methoxy-5-methylpyridine-3-boronic acidHCID 87555366HCID 87555366、化合物

生成物 1

HCID 68737513HCID 68737513、化合物収率 99.2%

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
120 °C

実験手順

To a mixture of N-(6-chloro-4-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (60 mg, 0.16 mmol) and 2-methoxy-5-methylpyridin-3-ylboronic acid (41 mg, 0.25 mmol) in DME (2 mL) and Na2CO3 (2M, 0.165 mL, 0.32 mmol) was added Pd(PPh3)4 (9.5 mg, 0.008 mmol). The mixture was heated in microwave oven at 120° C. for 30 min. The reaction was re-partitioned between EtOAc and H2O and the aqueous layer was extracted with ethyl acetate twice. The combined organic layers were washed with brine and dried over MgSO4. After the removal of solvent, the residue was purified by column chromatography (0-20% EtOAc-Hexane) to yield 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(2′-methoxy-4,5′-dimethyl-2,3′-bipyridin-6-yl)cyclopropanecarboxamide (72 mg, 97%). 1H NMR (400 MHz, CDCl3) 7.98 (s, 1H), 7.96 (dd, J=0.7, 2.4 Hz, 1H), 7.77 (d, J=2.3 Hz, 1H), 7.68 (s, 1H), 7.48 (d, J=9.0 Hz, 1H), 7.23 (dd, J=1.7, 9.4 Hz, 2H), 7.10 (d, J=8.2 Hz, 1H), 3.96 (s, 3H), 2.40 (s, 3H), 2.26 (s, 3H), 1.77-1.70 (m, 2H), 1.19-1.11 (m, 2H). Retention time: 2.01 min; ESI-MS m/z calc. 453.4. found 454.2 (M+H)+.

後処理

  1. customThe reaction was re-partitioned between EtOAc and H2O
  2. extractionthe aqueous layer was extracted with ethyl acetate twice
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. customAfter the removal of solvent
  6. customthe residue was purified by column chromatography (0-20% EtOAc-Hexane)

出典と根拠

ORDレコード
ord-a28c4e13db764d0184aecc733b7ac31a
出典データセット
uspto-grants-2015_03
特許番号
US08969386B2

反応ノート

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