Cesium carbonate → HCID 69079901, compound

HRID 2189334Notes

Reaction equation

HRID 2189334 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:14]([CH:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)[C:8]2[N:9]=[C:10](Cl)[N:11]=[CH:12][C:7]=2[C:6]=1[CH3:20])=[O:4].[C:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32][N:31]([C:34]2[CH:35]=[N:36][C:37]([NH2:40])=[CH:38][CH:39]=2)[CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>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]>[CH3:1][O:2][C:3]([C:5]1[N:14]([CH:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)[C:8]2[N:9]=[C:10]([NH:40][C:37]3[CH:38]=[CH:39][C:34]([N:31]4[CH2:32][CH2:33][N:28]([C:26]([O:25][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:27])[CH2:29][CH2:30]4)=[CH:35][N:36]=3)[N:11]=[CH:12][C:7]=2[C:6]=1[CH3:20])=[O:4]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 11737525tert-Butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylateHCID 866373522-chloro-7-cyclopentyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid methyl ester

Product 1

HCID 69079901HCID 69079901, compoundYield 17.5%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A mixture of 2-chloro-7-cyclopentyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid methyl ester (110 mg, 0.374 mmol), 4-(6-Amino-pyridin-3-yl)-piperazine-1-carboxylic acid tert-butyl ester (114.66 mg, 0.412 mmol), Pd2(dba)3 (17.144 mg, 0.02 mmol), Xantphos (21.67 mg, 0.037 mmol) and cesium carbonate (183 mg, 0.562 mmol) in dioxane (5 mL) is degassed and back-filled with nitrogen three times. The reaction mixture is heated to 100° C. for 4 h. Water is added and the solution is extracted with ethyl acetate three times. The organic layers are combined, washed with brine and dried over anhydrous sodium sulfate. The solvent is evaporated and the crude product is dissolved in a small amount of ethyl acetate. White solid precipitates out and filters to give 2-[5-(4-tert-Butoxycarbonyl-piperazin-1-yl)-pyridin-2-ylamino]-7-cyclopentyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid methyl ester as a white solid (35 mg, 17%) which was carried onto the next step without further purification. [M+H]+=536.35.

Workup

  1. customis degassed
  2. additionback-filled with nitrogen three times
  3. additionWater is added
  4. extractionthe solution is extracted with ethyl acetate three times
  5. washwashed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent is evaporated
  8. dissolutionthe crude product is dissolved in a small amount of ethyl acetate
  9. customWhite solid precipitates out and filters

Sources & evidence

ORD record
ord-7ce60a41f2184673a30b1c2b3c9a3da6
Source dataset
uspto-grants-2012_12
Patent number
US08324225B2

Reaction notes

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