Binap, (A+-)- → HCID 58015857, compound

HRID 2189300Notes

Reaction equation

HRID 2189300 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH3:11])=[CH:9][N:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=3)[C:6]=2[N:7]=1.C(OC([N:25]1[CH2:30][CH2:29][N:28]([C:31]2[CH:32]=[N:33][C:34]([NH2:37])=[CH:35][CH:36]=2)[CH2:27][CH2:26]1)=O)(C)(C)C.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.CC(C)([O-])C.[Na+]>C(OCC)(=O)C.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].O1CCOCC1>[CH3:11][C:10]1[C:5]2[CH:4]=[N:3][C:2]([NH:37][C:34]3[CH:35]=[CH:36][C:31]([N:28]4[CH2:27][CH2:26][NH:25][CH2:30][CH2:29]4)=[CH:32][N:33]=3)=[N:7][C:6]=2[N:8]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)[CH:9]=1

Participants

8

Reactant 4

HCID 634876Binap, (A+-)-HCID 11737525tert-Butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylateHCID 23676156Sodium t-butoxideHCID 866373417H-Pyrrolo[2,3-d]pyrimidine, 2-chloro-5-methyl-7-(2-pyridinyl)-

Product 1

HCID 58015857HCID 58015857, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-Chloro-5-methyl-7-pyridin-2-yl-7H-pyrrolo[2,3-d]pyrimidine (15 mg, 0.06 mmol), 4-(6-Amino-pyridin-3-yl)-piperazine-1-carboxylic acid tert-butyl ester (20.5 mg, 0.075 mmol), Pd2(dba)3 (2.8 mg, 0.0031 mmol), BINAP (3.82 mg, 0.0061 mmol), sodium tert-butoxide (8.84 mg, 0.092 mmol), and 1,4-dioxane (4 mL) under nitrogen is heated in a sealed tube apparatus at 100° C. for 2.5 h. After cooling to room temperature the reaction mixture is diluted with ethyl acetate and washed with brine. The organic phase is dried (anhydrous Na2SO4) and the solvent is evaporated. The crude product is dissolved in DCM (2 mL) and TFA (0.5 ml was added). The solution is stirred at room temperature. The reaction mixture is diluted with ethyl acetate and washed with brine. The organic phase is dried (anhydrous Na2SO4) and the solvent is evaporated. The crude product is purified by hplc to afford (5-Methyl-7-pyridin-2-yl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-(5-piperazin-1-yl-pyridin-2-yl)-amine as a pale yellow solid (27%, two steps). 1H NMR (400 MHz, DMSO-d6) 8.80-8.81 (m, 2H), 8.51 (s, 1H), 8.12 (d, J=5.0 Hz, 1H), 8.0-8.11 (m, 1H), 8.0 (d, J=2.9 Hz, 1H), 7.90 (s, 1H), 7.49 (d, J=2.4 Hz, 1H), 7.32 (d, J=2.4 Hz, 1H), 3.04-3.06 (m, 4H), (2.86-2.89 (m, 4H), 2.32 (s, 3H). MS (ESI) m/z 387.09 [M+H]+.

Workup

  1. temperatureAfter cooling to room temperature the reaction mixture
  2. washwashed with brine
  3. dry with materialThe organic phase is dried (anhydrous Na2SO4)
  4. customthe solvent is evaporated
  5. dissolutionThe crude product is dissolved in DCM (2 mL)
  6. additionThe reaction mixture is diluted with ethyl acetate
  7. washwashed with brine
  8. dry with materialThe organic phase is dried (anhydrous Na2SO4)
  9. customthe solvent is evaporated
  10. customThe crude product is purified by hplc

Sources & evidence

ORD record
ord-d4344c38623c43cc903f97399d44bbf5
Source dataset
uspto-grants-2012_12
Patent number
US08324225B2

Reaction notes

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