Sodium Carbonate → (4-methyl-piperazin-1-yl)-(4-{5-[2-(6-methyl-pyridin-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-pyridin-3-yl}-phenyl)-methanone

HRID 1878595Notes

Reaction equation

HRID 1878595 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2[C:9]3[CH:23]=[CH:22][NH:21][C:10]=3[N:11]=[C:12]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([CH3:20])[N:15]=3)[N:13]=2)[CH:5]=[N:6][CH:7]=1.[CH3:24][N:25]1[CH2:30][CH2:29][N:28]([C:31]([C:33]2[CH:38]=[CH:37][C:36](B3OC(C)(C)C(C)(C)O3)=[CH:35][CH:34]=2)=[O:32])[CH2:27][CH2:26]1.C([O-])([O-])=O.[Na+].[Na+].[OH-].[Na+]>COCCOC.CCO.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:24][N:25]1[CH2:30][CH2:29][N:28]([C:31]([C:33]2[CH:38]=[CH:37][C:36]([C:2]3[CH:7]=[N:6][CH:5]=[C:4]([C:8]4[C:9]5[CH:23]=[CH:22][NH:21][C:10]=5[N:11]=[C:12]([C:14]5[CH:19]=[CH:18][CH:17]=[C:16]([CH3:20])[N:15]=5)[N:13]=4)[CH:3]=3)=[CH:35][CH:34]=2)=[O:32])[CH2:27][CH2:26]1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 27600304-(4-Methylpiperazine-1-carbonyl)phenylboronic acid pinacol esterHCID 441944484-(5-Bromo-pyridin-3-yl)-2-(6-methyl-pyridin-2-yl)-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 44194349(4-methyl-piperazin-1-yl)-(4-{5-[2-(6-methyl-pyridin-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-pyridin-3-yl}-phenyl)-methanone

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 20074477Dimethoxyethane ethanolSolvent

Procedure

To a solution of 4-(5-bromo-pyridin-3-yl)-2-(6-methyl-pyridin-2-yl)-7H-pyrrolo[2,3-d]pyrimidine (Example 16) (1 eq, 0.273 mmol, 100 mg) and 4-(4-methylpiperazine-1-carbonyl)phenyl-boronic acid pinacol ester (ABCR GmbH & Co. KG, Karlsruhe, Germany) (1.1 eq, 0.300 mmol, 101 mg) in DME/EtOH (1:1, 2 ml), aqueous Na2CO3 solution (2 M, 3 eq, 0.82 mmol, 0.41 ml) and Pd(PPh3)4 (0.05 eq, 0.014 mmol, 16 mg) are added. The resulting mixture is heated using microwave radiation at 140° C. for 20 min. The mixture is diluted with water, basified with aqueous NaOH (1 M), extracted with DCM, and the organic layer is dried with MgSO4 and filtered. After evaporation of the solvent the crude product is purified by reversed phase HPLC giving the title compound; [M+H]+=490; 1H-NMR (400 MHz, CDCl3): δ 13.09 (s, 1H), 9.50 (d, 1H), 8.98 (d, 1H), 8.78 (d, 1H), 8.66 (d, 1H), 7.84 (t, 1H), 7.76 (d, 2H), 7.58 (d, 2H), 7.45 (m, 1H), 7.33 (d, 1H), 6.87 (d, 1H), 3.84 (m, 2H), 3.53 (m, 2H), 2.74 (s, 3H), 2.55-2.35 (m, 4H), 2.34 (s, 3H).

Workup

  1. temperatureThe resulting mixture is heated
  2. customat 140° C.
  3. customfor 20 min
  4. extractionextracted with DCM
  5. dry with materialthe organic layer is dried with MgSO4
  6. filtrationfiltered
  7. customAfter evaporation of the solvent the crude product
  8. customis purified by reversed phase HPLC

Sources & evidence

ORD record
ord-23ed0822b61b4b26a593e7acb2598a5e
Source dataset
uspto-grants-2012_11
Patent number
US08314112B2

Reaction notes

Loading…