Binap, (A+-)- → 4-{4-[7-(1-ethyl-propyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino]-phenyl}-piperazine-1-carboxylic acid tert-butyl ester

HRID 2189292Notes

Reaction equation

HRID 2189292 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(C)([O-])C.[Na+].Cl[C:28]1[N:29]=[CH:30][C:31]2[CH:36]=[CH:35][N:34]([CH:37]([CH2:40][CH3:41])[CH2:38][CH3:39])[C:32]=2[N:33]=1.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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:15]=[CH:16][C:17]([NH:20][C:28]3[N:29]=[CH:30][C:31]4[CH:36]=[CH:35][N:34]([CH:37]([CH2:40][CH3:41])[CH2:38][CH3:39])[C:32]=4[N:33]=3)=[CH:18][CH:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 634876Binap, (A+-)-HCID 11011301tert-Butyl 4-(4-aminophenyl)piperazine-1-carboxylateHCID 23676156Sodium t-butoxideHCID 580159322-Chloro-7-(pentan-3-yl)-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 690753604-{4-[7-(1-ethyl-propyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino]-phenyl}-piperazine-1-carboxylic acid tert-butyl esterYield 89.9%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
100 °C

Procedure

To a mixture of 4-(4-amino-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (133 mg, 0.48 mmol) and sodium tert-butoxide (57.6 mg, 0.6 mmol) in 1,4-dioxane (0.5 mL) is added a solution of 2-chloro-7-(1-ethyl-propyl)-7H-pyrrolo[2,3-d]pyrimidine (90 mg, 0.4 mmol) in 1,4-dioxane (1.0 mL), Pd2(dba)3 (18.3 mg, 0.02 mmol) and BINAP (25 mg, 0.04 mmol). The mixture is degassed, and heated at 100° C. for 3 h. The mixture is cooled to room temperature, diluted with EtOAc, and filtered through celite. The filtrate is concentrated under reduced pressure. The residue is purified by flash chromatography (SiO2, EtOAc:Hexane=1:1) to give 167 mg of 4-{4-[7-(1-ethyl-propyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino]-phenyl}-piperazine-1-carboxylic acid tert-butyl ester as a pale yellow solid.

Workup

  1. customThe mixture is degassed
  2. temperatureThe mixture is cooled to room temperature
  3. additiondiluted with EtOAc
  4. filtrationfiltered through celite
  5. concentrationThe filtrate is concentrated under reduced pressure
  6. customThe residue is purified by flash chromatography (SiO2, EtOAc:Hexane=1:1)

Sources & evidence

ORD record
ord-4316ac618800464baa98b6d2cfebf8fd
Source dataset
uspto-grants-2012_12
Patent number
US08324225B2

Reaction notes

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