Tetrahydrofuran → (4-(1H-Pyrazol-4-yl)-7H-pyrrolo(2,3-d)pyrimidin-7-yl)methyl pivalate

HRID 1467434Notes

Reaction equation

HRID 1467434 reaction equation
[C:1]([O:7][CH2:8][N:9]1[C:13]2[N:14]=[CH:15][N:16]=[C:17]([C:18]3[CH:19]=[N:20][N:21](C(OCC)C)[CH:22]=3)[C:12]=2[CH:11]=[CH:10]1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].C1COCC1.[OH-].[Na+]>Cl>[C:1]([O:7][CH2:8][N:9]1[C:13]2[N:14]=[CH:15][N:16]=[C:17]([C:18]3[CH:19]=[N:20][NH:21][CH:22]=3)[C:12]=2[CH:11]=[CH:10]1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 57868870(4-(1-(1-Ethoxyethyl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate

Product 1

HCID 57868869(4-(1H-Pyrazol-4-yl)-7H-pyrrolo(2,3-d)pyrimidin-7-yl)methyl pivalateYield 77%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

To a solution of crude {4-[1-(1-ethoxyethyl)-1H-pyrazol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-7-yl]methyl pivalate (4) in THF (1 L, 12.3 mol), a 4 N aqueous HCl solution (500 mL) was added at room temperature. The resulting reaction mixture was subsequently stirred at room temperature for 5 h. When the reaction was deemed complete as confirmed by TLC and LCMS, the reaction mixture was cooled to 0-5° C. before pH was adjusted to 9-10 with a 1 M aqueous sodium hydroxide (NaOH) solution (2 L). The mixture was concentrated under reduced pressure to remove most of THF and the resulting suspension was stirred at room temperature for 2 h. The solids were collected by filtration, washed with water (3×500 mL), and dried in vacuum to afford crude [4-(1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]methyl pivalate (5, 157.5 g, 204.43 g theoretical, 77% yield for three steps) as white to off-white solids, which was found to be sufficiently pure (>98 area % by HPLC) to do the subsequent reaction without further purification. For 5: 1H NMR (DMSO-d6, 400 MHz) δ ppm 13.42 (br s, 1H), 8.76 (s, 1H), 8.67 (s, 1H), 8.33 (s, 1H), 7.68 (d, 1H, J=3.8 Hz), 7.11 (d, 1H, J=3.8 Hz), 6.21 (s, 2H), 1.06 (s, 9H); 13C NMR (DMSO-d6, 100 MHz) δ ppm 177.74, 152.31, 152.09, 151.91, 139.52, 130.39, 120.51, 113.93, 101.91, 67.26, 38.98, 27.26; C15H17N5O2 (MW, 299.33), LCMS (EI) m/e 300 (M++H).

Workup

  1. customThe resulting reaction mixture
  2. temperaturethe reaction mixture was cooled to 0-5° C. before pH
  3. concentrationThe mixture was concentrated under reduced pressure
  4. customto remove most of THF
  5. stirringthe resulting suspension was stirred at room temperature for 2 h
  6. filtrationThe solids were collected by filtration
  7. washwashed with water (3×500 mL)
  8. customdried in vacuum

Sources & evidence

ORD record
ord-fda287d11c1c4aa0a153cec836f7b943
Source dataset
uspto-grants-2015_04
Patent number
US09000161B2

Reaction notes

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