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Cesium carbonate → tert-butyl 9-((5-chloro-2-((1-methyl-1H-imidazol-4-yl)amino)pyrimidin-4-yl)amino)-3-azaspiro[5.5]undecane-3-carboxylate

HRID 1478047
Notes
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Reaction equation

HRID 1478047 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][CH:9]2[CH2:14][CH2:13][C:12]3([CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]3)[CH2:11][CH2:10]2)[C:5]([Cl:27])=[CH:4][N:3]=1.[CH3:28][N:29]1[CH:33]=[C:32]([NH2:34])[N:31]=[CH:30]1.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:27][C:5]1[C:6]([NH:8][CH:9]2[CH2:10][CH2:11][C:12]3([CH2:15][CH2:16][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:24])[CH3:25])=[O:21])[CH2:18][CH2:19]3)[CH2:13][CH2:14]2)=[N:7][C:2]([NH:34][C:32]2[N:31]=[CH:30][N:29]([CH3:28])[CH:33]=2)=[N:3][CH:4]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 108986491-Methyl-1H-imidazol-4-amineHCID 118390013Tert-butyl 3-[(2,5-dichloropyrimidin-4-yl)amino]-9-azaspiro[5.5]undecane-9-carboxylate

Product 1

HCID 118389996tert-butyl 9-((5-chloro-2-((1-methyl-1H-imidazol-4-yl)amino)pyrimidin-4-yl)amino)-3-azaspiro[5.5]undecane-3-carboxylate
Yield 50.97%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of tert-butyl 3-[(2,5-dichloropyrimidin-4-yl)amino]-9-azaspiro[5.5]undecane-9-carboxylate (500 mg, 1.204 mmol), 1-methylimidazol-4-amine (176.1 mg, 1.813 mmol) and cesium carbonate (1.19 g, 3.65 mmol) in anhydrous dioxane (10 mL) were added BINAP (148.6 mg, 0.2386 mmol) and Pd(OAc)2 (54.1 mg, 0.241 mmol). The reaction was under an inert atmosphere and stirred at 150° C. under microwave irradiation for 2 h. The reaction solution was concentrated in vacuo and the residue was purified by silica gel column chromatography with (DCM/MeOH (v/v)=30/1) to give the title compound as a yellow solid (292 mg, 50.97%).

Workup

  1. concentrationThe reaction solution was concentrated in vacuo
  2. customthe residue was purified by silica gel column chromatography with (DCM/MeOH (v/v)=30/1)

Sources & evidence

ORD record
ord-a1f87d6ca56a440e8e8b317dc0133db0
Source dataset
uspto-grants-2016_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09403801B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes