Iodine → (R)-(4-(1-(2-cyano-1-cyclopentylethyl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate

HRID 1467456Notes

Reaction equation

HRID 1467456 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@@H:23]([CH:27]4[CH2:31][CH2:30][CH2:29][CH2:28]4)[CH2:24][CH:25]=O)[CH:22]=3)[C:12]=2[CH:11]=[CH:10]1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].O1CCCC1.[OH-].[NH4+:38].II>O>[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@@H:23]([CH:27]4[CH2:31][CH2:30][CH2:29][CH2:28]4)[CH2:24][C:25]#[N:38])[CH:22]=3)[C:12]=2[CH:11]=[CH:10]1)(=[O:6])[C:2]([CH3:4])([CH3:5])[CH3:3]

Participants

6

Reactant 4

HCID 807IodineHCID 8028TetrahydrofuranHCID 14923Ammonium HydroxideHCID 59420185(1R)-(4-(1-(1-cyclopentyl-3-oxopropyl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate

Product 1

HCID 59420145(R)-(4-(1-(2-cyano-1-cyclopentylethyl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalateYield 86.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of (1R)-(4-(1-(1-cyclopentyl-3-oxopropyl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate ((R)-37, 169 mg, 0.399 mmol) in tetrahydrofuran (THF, 1.2 mL, 15 mmol) at room temperature was added a 14.3 M solution of ammonium hydroxide (NH4OH) in water (1.2 mL), followed by iodine (I2, 112 mg, 0.439 mmol, 1.1 equiv). The resulting reaction mixture was stirred at room temperature for 25 min. When LCMS showed that the reaction was deemed complete, the reaction mixture was quenched with 10% aqueous Na2S2O3 (10 mL) before being extracted with EtOAc (2×15 mL). The combined organic layers were washed with brine, dried over magnesium sulfate (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by Combiflash (SiO2) with 0-60% EtOAc/hexane gradient elution to afford (R)-(4-(1-(2-cyano-1-cyclopentylethyl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate ((R)-12, 145.6 mg, 167.8 mg theoretical, 86.8% yield) as a colorless foam.

Workup

  1. customThe resulting reaction mixture
  2. customthe reaction mixture was quenched with 10% aqueous Na2S2O3 (10 mL)
  3. extractionbefore being extracted with EtOAc (2×15 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over magnesium sulfate (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by Combiflash (SiO2) with 0-60% EtOAc/hexane gradient elution

Sources & evidence

ORD record
ord-b6939768148642b89992d97cda567021
Source dataset
uspto-grants-2015_04
Patent number
US09000161B2

Reaction notes

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