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 877050Notes

Reaction equation

HRID 877050 reaction equation
[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]

Participants

7

Reactant 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

Product 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

Reagents, catalysts & solvents 3

HCID 178477754HCID 178477754, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-f78e78a895674c169e1203c6207284a3
Source dataset
uspto-grants-2015_03
Patent number
US08987286B2

Reaction notes

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