Acetic Acid → (R)-4-[1-(2-cyano-1-cyclopentylethyl)-1H-pyrazol-4-yl]-2-methoxy-7H-pyrrolo[2,3-d]pyrimidin-5-yl acetate

HRID 403192Notes

Reaction equation

HRID 403192 reaction equation
[CH:1]1([CH:6]([N:10]2[CH:14]=[C:13]([C:15]3[C:16]4[C:25](I)=[CH:24][NH:23][C:17]=4[N:18]=[C:19]([O:21][CH3:22])[N:20]=3)[CH:12]=[N:11]2)[CH2:7][C:8]#[N:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.[C:27]([OH:30])(=[O:29])[CH3:28]>C([O-])(=O)C.[Ag+]>[C:27]([O:30][C:25]1[C:16]2[C:15]([C:13]3[CH:12]=[N:11][N:10]([C@@H:6]([CH:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)[CH2:7][C:8]#[N:9])[CH:14]=3)=[N:20][C:19]([O:21][CH3:22])=[N:18][C:17]=2[NH:23][CH:24]=1)(=[O:29])[CH3:28]

Participants

4

Reactant 2

HCID 176Acetic AcidHCID 670948833-cyclopentyl-3-[4-(5-iodo-2-methoxy-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile

Product 1

HCID 58220995(R)-4-[1-(2-cyano-1-cyclopentylethyl)-1H-pyrazol-4-yl]-2-methoxy-7H-pyrrolo[2,3-d]pyrimidin-5-yl acetate

Reagents, catalysts & solvents 1

HCID 11246Silver acetateCatalyst

Conditions

Temperature
70 °C

Procedure

A solution of 3-cyclopentyl-3-[4-(5-iodo-2-methoxy-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile (0.25 g, 0.54 mmol) in acetic acid (3 mL) was treated with silver acetate (0.27 g, 1.6 mmol) and heated to 70° C. for 16 h. The mixture was filtered, rinsed with MeCN, water was added to the filtrate and this mixture was stirred for 20 min, Solid sodium chloride was added to this solution. The product was obtained by extraction of this aqueous mixture with three portions of ethyl acetate. The combined extracts were dried over sodium sulfate, decanted and concentrated. A portion of the product was used in the hydrolysis step (Step 4) without further purification. 1H NMR (300 MHz, CDCl3): δ 9.87 (br s, 1H), 8.39 (s, 1H), 8.37 (s, 1H), 7.33 (s, 1H), 4.22 (dt, 1H), 4.06 (s, 3H), 3.14 (dd, 1H), 2.94 (dd, 1H), 2.64-2.47 (m, 1H), 2.36 (s, 3H), 2.03-1.86 (m, 1H), 1.79-1.12 (m, 7H); LCMS (M+H)+: 395.1.

Workup

  1. filtrationThe mixture was filtered
  2. washrinsed with MeCN, water
  3. additionwas added to the filtrate
  4. additionSolid sodium chloride was added to this solution
  5. customThe product was obtained by extraction of this aqueous mixture with three portions of ethyl acetate
  6. dry with materialThe combined extracts were dried over sodium sulfate
  7. customdecanted
  8. concentrationconcentrated
  9. customA portion of the product was used in the hydrolysis step (Step 4) without further purification

Sources & evidence

ORD record
ord-40c6cf35c00f49dc921d28378762ae4a
Source dataset
uspto-grants-2014_06
Patent number
US08748401B2

Reaction notes

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