Sodium Carbonate → 5-[2-(4-{1-[(Tert-butoxycarbonyl)amino]cyclobutyl}phenyl)-3-phenylpyrimido[1,2-b]indazol-8-yl]pyrazole-1-carboxylic acid tert-butyl ester

HRID 877050Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 877050
[C:1]([O:5][C:6](=[O:38])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:31]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)=[CH:30][N:21]4[N:22]=[C:23]5[C:28]([CH:27]=[CH:26][C:25](Br)=[CH:24]5)=[C:20]4[N:19]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[C:39]([O:43][C:44]([N:46]1[C:50](B(O)O)=[CH:49][CH:48]=[N:47]1)=[O:45])([CH3:42])([CH3:41])[CH3:40].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe]>[C:39]([O:43][C:44]([N:46]1[C:50]([C:25]2[CH:26]=[CH:27][C:28]3[C:23]([CH:24]=2)=[N:22][N:21]2[CH:30]=[C:31]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)[C:18]([C:15]4[CH:16]=[CH:17][C:12]([C:8]5([NH:7][C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:38])[CH2:11][CH2:10][CH2:9]5)=[CH:13][CH:14]=4)=[N:19][C:20]=32)=[CH:49][CH:48]=[N:47]1)=[O:45])([CH3:42])([CH3:40])[CH3:41]

Komponenten

7

Edukt 3

HCID 10340Sodium CarbonateHCID 467389241H-Pyrazole-5-boronic acid, N1-BOC protectedHCID 86702528{1-[4-(8-Bromo-3-phenylpyrimido[1,2-b]indazol-2-yl)phenyl]-cyclobutyl}carbamic acid tert-butyl ester

Produkt 1

HCID 679912345-[2-(4-{1-[(Tert-butoxycarbonyl)amino]cyclobutyl}phenyl)-3-phenylpyrimido[1,2-b]indazol-8-yl]pyrazole-1-carboxylic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178477754HCID 178477754, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
105 °C

Versuchsvorschrift

100 mg (0.18 mmol) {1-[4-(8-Bromo-3-phenylpyrimido[1,2-b]indazol-2-yl)phenyl]-cyclobutyl}carbamic acid tert-butyl ester, intermediate example Int-2-2, 74.5 mg (0.35 mmol) [1-(tert-butoxycarbonyl)-1H-pyrazol-5-yl]boronic acid, 14.3 mg (0.02 mmol) 1,1 bis(diphenylphosphino)ferrocenedichloro-palladium(II) and 55.8 mg (0.53 mmol) sodium carbonate in 1.8 mL dioxane and 0.3 mL water (both solvents had been degassed) were heated in the microwave for 30′ at 105° C. The reaction mixture was poured on water/dichloromethane/saturated ammonium chloride and vigorously stirred for 30′. The organic phase was separated, washed twice with brine, dried (sodium sulfate) and filtrated. The solvent was evaporated and the crude residue (181 mg>100%) was used in the next step without further purification.

Aufarbeitung

  1. additionThe reaction mixture was poured on water/dichloromethane/saturated ammonium chloride
  2. customThe organic phase was separated
  3. washwashed twice with brine
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltrated
  6. customThe solvent was evaporated
  7. customthe crude residue (181 mg>100%) was used in the next step without further purification

Quellen und Nachweise

ORD-Eintrag
ord-f78e78a895674c169e1203c6207284a3
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08987286B2

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