Sodium Carbonate → HCID 68737513, 화합물

HRID 869953노트

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HRID 869953 반응식
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

참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 27631282-Methoxy-5-methylpyridine-3-boronic acidHCID 87555366HCID 87555366, 화합물

생성물 1

HCID 68737513HCID 68737513, 화합물수율 99.2%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 80711,2-Dimethoxyethane용매

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온도
120 °C

실험 절차

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)+.

후처리

  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)

출처 및 근거

ORD 기록
ord-a28c4e13db764d0184aecc733b7ac31a
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08969386B2

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