Sodium Carbonate → HCID 67959573, 화합물

HRID 1529386노트

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HRID 1529386 반응식
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

참가 물질

7

반응물 3

HCID 10340Sodium CarbonateHCID 38742473-(Cyclopropylaminocarbonyl)phenylboronic acidHCID 67959732HCID 67959732, 화합물

생성물 1

HCID 67959573HCID 67959573, 화합물수율 82%

시약·촉매·용매 3

HCID 178418476HCID 178418476, 화합물촉매HCID 962Water용매HCID 312751,4-Dioxane용매

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온도
120 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-f2d09b313fd54372883a61908200bd3e
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09090593B2

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