1,3-dimethyl-1H-pyrazol-4-amine → 4-(4-Cyclobutoxy-2-((1,3-dimethyl-1H-pyrazol-4-yl)amino)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-N-methylbenzamide

HRID 1487688Notes

Reaction equation

HRID 1487688 reaction equation
Cl[C:2]1[N:3]=[C:4]([O:29][CH:30]2[CH2:33][CH2:32][CH2:31]2)[C:5]2[C:10]([C:11]3[CH:20]=[CH:19][C:14]([C:15]([NH:17][CH3:18])=[O:16])=[CH:13][CH:12]=3)=[CH:9][N:8]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:6]=2[N:7]=1.[CH3:34][N:35]1[CH:39]=[C:38]([NH2:40])[C:37]([CH3:41])=[N:36]1.CC(C)([O-])C.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC(C)C)=CC=CC=2OC(C)C)CCCCC1>O1CCOCC1>[CH:30]1([O:29][C:4]2[C:5]3[C:10]([C:11]4[CH:20]=[CH:19][C:14]([C:15]([NH:17][CH3:18])=[O:16])=[CH:13][CH:12]=4)=[CH:9][N:8]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:6]=3[N:7]=[C:2]([NH:40][C:38]3[C:37]([CH3:41])=[N:36][N:35]([CH3:34])[CH:39]=3)[N:3]=2)[CH2:33][CH2:32][CH2:31]1

Participants

6

Reactant 4

HCID 44310561,3-dimethyl-1H-pyrazol-4-amineHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 23676156Sodium t-butoxideHCID 867264544-(2-Chloro-4-cyclobutoxy-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-N-methylbenzamide

Product 1

HCID 867265154-(4-Cyclobutoxy-2-((1,3-dimethyl-1H-pyrazol-4-yl)amino)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-N-methylbenzamideYield 37%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a degassed mixture of 4-(2-chloro-4-cyclobutoxy-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-N-methylbenzamide (1 equiv), 1,3-dimethyl-1H-pyrazol-4-amine (1 equiv) and sodium tert-butoxide (2 equiv) in 1,4-dioxane (0.15 M) was added chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2′,4′,6′-tri-1-propyl-1,1′-biphenyl][2-(2-aminoethyl)phenyl]palladium(II), (0.06 equiv) and dicyclohexyl(2′,6′-diisopropoxy-[1,1′-biphenyl]-2-yl)phosphine (0.06 equiv). The reaction was stirred at 100° C. for 16 h. The reaction mixture was cooled to room temperature, and concentrated. The residue was purified by silica gel chromatography (0-5% MeOH in DCM) to afford the title compound (37% yield). MS (ESI) m/z 562.3 [M+1]+.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. concentrationconcentrated
  3. customThe residue was purified by silica gel chromatography (0-5% MeOH in DCM)

Sources & evidence

ORD record
ord-ae5ff0a2951d41e2bec7fe0513f25f75
Source dataset
uspto-grants-2016_08
Patent number
US09428509B2

Reaction notes

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