N-Methyl-N-[(3R,4R)-4-methylpiperidin-3-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine → Tofacitinib

HRID 1594375Notes

Reaction equation

HRID 1594375 reaction equation
[CH3:1][N:2]([C@@H:12]1[C@H:17]([CH3:18])[CH2:16][CH2:15][NH:14][CH2:13]1)[C:3]1[C:4]2[CH:11]=[CH:10][NH:9][C:5]=2[N:6]=[CH:7][N:8]=1.O=C1CCC(=O)N1[O:26][C:27](=O)[CH2:28][C:29]#[N:30]>C(O)C>[CH3:18][C@@H:17]1[CH2:16][CH2:15][N:14]([C:27](=[O:26])[CH2:28][C:29]#[N:30])[CH2:13][C@@H:12]1[N:2]([CH3:1])[C:3]1[C:4]2[CH:11]=[CH:10][NH:9][C:5]=2[N:6]=[CH:7][N:8]=1

Participants

4

Reactant 2

HCID 23401507N-Methyl-N-[(3R,4R)-4-methylpiperidin-3-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amineHCID 534158962,5-Dioxopyrrolidin-1-yl 2-cyanoacetate

Product 1

HCID 9926791TofacitinibYield 86.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a stirred solution of the product from Method B (1.0 g) dissolved in 30 mL of ethanol was added 0.82 g of cyano-acetic acid 2,5-dioxo-pyrrolidin-1-yl ester and the resulting mixture stirred at room temperature for 2 h. The reaction mixture was filtered through Celite® and concentrated in vacuo. The residue was redissolved in dichloromethane, washed with saturated, aqueous sodium bicarbonate, dried over sodium sulfate, filtered and concentrated to dryness in vacuo affording 1.1 g (86%) of the title compound as a yellow foam. LRMS: 313 (M+1).

Workup

  1. filtrationThe reaction mixture was filtered through Celite®
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was redissolved in dichloromethane
  4. washwashed with saturated, aqueous sodium bicarbonate
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness in vacuo

Sources & evidence

ORD record
ord-fab41313f5474ba3a29c20fae2961a36
Source dataset
uspto-grants-2007_11
Patent number
US07301023B2

Reaction notes

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