Sodium Carbonate → HCID 67959573、化合物

HRID 1529386ノート

反応式

HRID 1529386 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[N:6]=[C:5]2[C:17]1[N:22]=[C:21]([O:23][C@H:24]2[CH2:31][N:30]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:29][CH2:28][C:25]32[CH2:27][CH2:26]3)[CH:20]=[N:19][CH:18]=1.[CH:39]1([NH:42][C:43]([C:45]2[CH:46]=[C:47](B(O)O)[CH:48]=[CH:49][CH:50]=2)=[O:44])[CH2:41][CH2:40]1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH:39]1([NH:42][C:43]([C:45]2[CH:50]=[C:49]([C:2]3[CH:3]=[C:4]4[C:8](=[CH:9][CH:10]=3)[N:7]([CH:11]3[CH2:16][CH2:15][CH2:14][CH2:13][O:12]3)[N:6]=[C:5]4[C:17]3[N:22]=[C:21]([O:23][C@H:24]4[CH2:31][N:30]([C:32]([O:34][C:35]([CH3:36])([CH3:38])[CH3:37])=[O:33])[CH2:29][CH2:28][C:25]54[CH2:27][CH2:26]5)[CH:20]=[N:19][CH:18]=3)[CH:48]=[CH:47][CH:46]=2)=[O:44])[CH2:40][CH2:41]1

参加物

7

反応物 3

HCID 10340Sodium CarbonateHCID 38742473-(Cyclopropylaminocarbonyl)phenylboronic acidHCID 67959732HCID 67959732、化合物

生成物 1

HCID 67959573HCID 67959573、化合物収率 82%

試薬・触媒・溶媒 3

HCID 178418476HCID 178418476、化合物触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
120 °C

実験手順

A glass microwave reaction vessel was charged with (4R)-tert-butyl 4-(6-(5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)-6-azaspiro[2.5]octane-6-carboxylate (115 mg, 0.20 mmol), 3-(cyclopropylcarbamoyl)phenylboronic acid (81 mg, 0.39 mmol), PdCl2(PPh3)2 (11 mg, 0.016 mmol) and Na2CO3 (104 mg, 0.98 mmol) in dioxane (0.8 mL) and water (0.2 mL). The reaction was stirred and heated in a Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 120° C. for 20 min. The layers were separated and the organic phase was dried over anhydrous Na2SO4, filtered and concentrated. The crude was purified by silica gel chromatography, eluting with a gradient of 0-75% EtOAc in hexanes, to provide (4R)-tert-butyl 4-(6-(5-(3-(cyclopropylcarbamoyl)phenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)-6-azaspiro[2.5]octane-6-carboxylate (107 mg, 0.16 mmol, 82% yield) as a clear, colorless oil. MS (ESI, pos. ion) m/z: 665.3 (M+1).

後処理

  1. customA glass microwave reaction vessel
  2. customThe layers were separated
  3. dry with materialthe organic phase was dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude was purified by silica gel chromatography
  7. washeluting with a gradient of 0-75% EtOAc in hexanes

出典と根拠

ORDレコード
ord-f2d09b313fd54372883a61908200bd3e
出典データセット
uspto-grants-2015_07
特許番号
US09090593B2

反応ノート

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