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Sodium Carbonate → 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(5-methyl-6-(3-oxo-1,3-dihydroisobenzofuran-5-yl)pyridin-2-yl)cyclopropanecarboxamide

HRID 1442837
ノート
印刷プレビュー

反応式

HRID 1442837 の反応式
CC1(C)C(C)(C)OB([C:9]2[CH:17]=[C:16]3[C:12]([CH2:13][O:14][C:15]3=[O:18])=[CH:11][CH:10]=2)O1.Cl[C:21]1[N:26]=[C:25]([NH:27][C:28]([C:30]2([C:33]3[CH:43]=[CH:42][C:36]4[O:37][C:38]([F:41])([F:40])[O:39][C:35]=4[CH:34]=3)[CH2:32][CH2:31]2)=[O:29])[CH:24]=[CH:23][C:22]=1[CH3:44].C([O-])([O-])=O.[Na+].[Na+]>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.COCCOC>[F:41][C:38]1([F:40])[O:37][C:36]2[CH:42]=[CH:43][C:33]([C:30]3([C:28]([NH:27][C:25]4[CH:24]=[CH:23][C:22]([CH3:44])=[C:21]([C:9]5[CH:17]=[C:16]6[C:12](=[CH:11][CH:10]=5)[CH2:13][O:14][C:15]6=[O:18])[N:26]=4)=[O:29])[CH2:32][CH2:31]3)=[CH:34][C:35]=2[O:39]1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 59165796N-(6-chloro-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropane-1-carboxamideHCID 591659366-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1(3H)-isobenzofuranone

生成物 1

HCID 591661131-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(5-methyl-6-(3-oxo-1,3-dihydroisobenzofuran-5-yl)pyridin-2-yl)cyclopropanecarboxamide

試薬・触媒・溶媒 2

HCID 178418397
HCID 178418397、化合物
触媒
HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
120 °C

実験手順

6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isobenzofuran-1(3H)-one (39 mg, 0.15 mmol), N-(6-chloro-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (37 mg, 0.10 mmol) and Pd(PPh3)4 (6 mg, 0.005 mmol) were placed in a microwave vial. DME (1 mL) and saturated aq. Na2CO3 (100 μL) were added and the reaction vial was flushed with N2 and sealed. The reaction was heated in the microwave at 120° C. for 20 minutes before it was partitioned between ethyl acetate and H2O. The organic layer was filtered and concentrated. The residue was dissolved in DMSO and purified by reverse-phase HPLC to yield 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(5-methyl-6-(3-oxo-1,3-dihydroisobenzofuran-5-yl)pyridin-2-yl)cyclopropanecarboxamide. ESI-MS m/z calc. 464.1, found 465.3 (M+1)+. Retention time 1.96 minutes. 1H NMR (400 MHz, DMSO-d6) δ 8.99 (s, 1H), 7.94-7.86 (m, 3H), 7.76-7.73 (m, 2H), 7.56 (d, J=1.5 Hz, 1H), 7.41-7.33 (m, 2H), 5.47 (s, 2H), 2.26 (s, 3H), 1.53-1.50 (m, 2H), 1.19-1.16 (m, 2H).

後処理

  1. customthe reaction
  2. customvial was flushed with N2
  3. customsealed
  4. customwas partitioned between ethyl acetate and H2O
  5. filtrationThe organic layer was filtered
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in DMSO
  8. custompurified by reverse-phase HPLC

出典と根拠

ORDレコード
ord-e1cc49ba7d0947f9bd7afaed4cd4c18f
出典データセット
uspto-grants-2010_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07659268B2

反応ノート

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