N-methyl-2-pyrrolidone → HCID 86677718, compound

HRID 1499791Notes

Reaction equation

HRID 1499791 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:14]([C:16]3[C:17]([O:35][CH3:36])=[C:18]([CH:24]4[CH2:27][N:26]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:25]4)[C:19]([CH3:23])=[C:20](Cl)[CH:21]=3)[CH3:15])[N:9]=[C:10]([CH:11]([F:13])[F:12])[C:3]=12.[CH3:37][N:38]1CCCC1=O>[Zn].CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.[C-]#N.[Zn+2].[C-]#N>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:14]([C:16]3[C:17]([O:35][CH3:36])=[C:18]([CH:24]4[CH2:27][N:26]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:25]4)[C:19]([CH3:23])=[C:20]([C:37]#[N:38])[CH:21]=3)[CH3:15])[N:9]=[C:10]([CH:11]([F:13])[F:12])[C:3]=12

Participants

6

Reactant 2

HCID 13387N-methyl-2-pyrrolidoneHCID 86677716HCID 86677716, compound

Product 1

HCID 86677718HCID 86677718, compoundYield 96%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 178418851HCID 178418851, compoundCatalyst

Conditions

Temperature
130 °C

Procedure

Zinc (11 mg, 0.17 mmol) and bis(tri-t-butylphosphine)palladium (71 mg, 0.14 mmol) were weighed into a microwave vial then a solution of tert-butyl 3-(3-{1-[4-amino-3-(difluoromethyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]ethyl}-5-chloro-2-methoxy-6-methylphenyl)azetidine-1-carboxylate (182 mg, 0.348 mmol, racemic intermediate from Examples 127/128, step 4) in N-methylpyrrolidinone (2.0 mL) was added. The mixture was degassed with N2 for a few minutes before adding zinc cyanide (82 mg, 0.70 mmol). The resulting mixture was stirred at 130° C. for 3 h. After cooling, the mixture was filtered through a pad of Celite and concentrated. The crude was purified on silica gel, eluted with 0-5% MeOH in dichloromethane. The product eluted right away, along with NMP. The fractions were combined and concentrated then taken up in EtOAc and washed with brine (3×). The organic was dried, filtered, and concentrated to give 0.17 g (96%) of the desired product. LCMS calculated for C25H30F2N7O3 (M+H)+: m/z=514.2; Found: 514.1.

Workup

  1. customThe mixture was degassed with N2 for a few minutes
  2. temperatureAfter cooling
  3. filtrationthe mixture was filtered through a pad of Celite
  4. concentrationconcentrated
  5. customThe crude was purified on silica gel
  6. washeluted with 0-5% MeOH in dichloromethane
  7. washThe product eluted right away, along with NMP
  8. concentrationconcentrated
  9. washwashed with brine (3×)
  10. customThe organic was dried
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-2826fc11f8a5449b8b62569b76626847
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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