Sodium Carbonate → HCID 67959573, compound

HRID 1529386Notes

Reaction equation

HRID 1529386 reaction equation
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

Participants

7

Reactant 3

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

Product 1

HCID 67959573HCID 67959573, compoundYield 82%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-f2d09b313fd54372883a61908200bd3e
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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