Ethyl Acetate → HCID 59834738, compound

HRID 271565Notes

Reaction equation

HRID 271565 reaction equation
[CH3:1][C:2]([CH3:32])([CH3:31])[CH2:3][N:4]1[C:8]2[N:9]=[C:10]([C:13]#[N:14])[N:11]=[CH:12][C:7]=2[CH:6]=[C:5]1[CH2:15][N:16]1[CH2:21][CH2:20][N:19]([C:22]2N=CC([N+]([O-])=O)=CN=2)[CH2:18][CH2:17]1.[CH3:33][S:34](Cl)(=[O:36])=[O:35].CCO[C:41]([CH3:43])=O>CO.N1C=CC=CC=1.O=[Pt]=O>[C:13]([C:10]1[N:11]=[CH:12][C:7]2[CH:6]=[C:5]([CH2:15][N:16]3[CH2:21][CH2:20][N:19]([C:22]4[CH:43]=[CH:41][C:3]([NH:4][S:34]([CH3:33])(=[O:36])=[O:35])=[CH:2][CH:1]=4)[CH2:18][CH2:17]3)[N:4]([CH2:3][C:2]([CH3:31])([CH3:32])[CH3:1])[C:8]=2[N:9]=1)#[N:14]

Participants

7

Reactant 3

HCID 8857Ethyl AcetateHCID 31297Methanesulfonyl chlorideHCID 68927817HCID 68927817, compound

Product 1

HCID 59834738HCID 59834738, compoundYield 49%

Reagents, catalysts & solvents 3

HCID 345198Adams' catalystCatalystHCID 887MethanolSolventHCID 1049PyridineSolvent

Procedure

To a suspension of catalytic amount of PtO2 in MeOH (20 ml) and AcOEt (20 ml), 7-(2,2-dimethyl-propyl)-6-[4-(5-nitro-pyrimidin-2-yl)-piperazin-1-ylmethyl]-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile (1.15 mmol) is added and the mixture is stirred under H2 atmosphere. After being stirred for 3 h, the reaction mixture is filtered through celite and concentrated under reduced pressure to give crude amine. To a solution of the crude amine in pyridine (10 ml), methanesulfonyl chloride (1.99 mmol) is added at 0° C. and the mixture is allowed to warm to ambient temperature and stirred for 2 h. The reaction mixture is poured into ice water and extracted with AcOEt. The combined extracts are washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (eluent; n-hexane:AcOEt=1:1) to give 296 mg of desired N-(4-{4-[2-cyano-7-(2,2-dimethyl-propyl)-7H-pyrrolo[2,3-d]pyrimidin-6-ylmethyl]-piperazin-1-yl}-phenyl)-methanesulfonamide in 49% yield. Rf=0.52 (AcOEt only). 1H NMR (400 MHz, CDCl3) δ 1.02 (s, 9H), 2.55-2.65 (m, 4H), 2.94 (s, 3H), 3.15-3.25 (m, 4H), 3.85 (s, 2H), 4.37 (s, 2H), 6.17 (brs, 1H), 6.61 (s, 1H), 6.88 (d, 2H), 7.15 (d, 2H), 8.91 (s, 1H)

Workup

  1. additionis added
  2. stirringAfter being stirred for 3 h
  3. filtrationthe reaction mixture is filtered through celite and
  4. concentrationconcentrated under reduced pressure
  5. customto give crude amine
  6. stirringstirred for 2 h
  7. extractionextracted with AcOEt
  8. washThe combined extracts are washed with brine
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe residue is purified by silica gel column chromatography (eluent; n-hexane:AcOEt=1:1)

Sources & evidence

ORD record
ord-5d17591f5d974dea8e2b0488c13485f9
Source dataset
uspto-grants-2008_11
Patent number
US07452886B2

Reaction notes

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