Diisopropylethylamine → HCID 86692136, compound

HRID 527902Notes

Reaction equation

HRID 527902 reaction equation
[CH3:1][Si:2]([CH3:30])([CH3:29])[CH2:3][CH2:4][O:5][CH2:6][N:7]1[C:11]2[N:12]=[CH:13][N:14]=[C:15]([N:16]3[CH2:20][CH2:19][C@@H:18]([NH:21][C:22](=O)OC(C)(C)C)[CH2:17]3)[C:10]=2[CH:9]=[CH:8]1.ClC1[CH:39]=[CH:38][C:35]([C:36]#[N:37])=[CH:34][N:33]=1.CCN(C(C)C)C(C)C>Cl.O>[CH3:29][Si:2]([CH3:30])([CH3:1])[CH2:3][CH2:4][O:5][CH2:6][N:7]1[C:11]2[N:12]=[CH:13][N:14]=[C:15]([N:16]3[CH2:20][CH2:19][C@@H:18]([NH:21][C:22]4[CH:39]=[CH:38][C:35]([C:36]#[N:37])=[CH:34][N:33]=4)[CH2:17]3)[C:10]=2[CH:9]=[CH:8]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 51520946-Chloro-3-pyridinecarbonitrileHCID 68029225HCID 68029225, compound

Product 1

HCID 86692136HCID 86692136, compound

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

A solution of (R)-tert-butyl 1-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrrolidin-3-ylcarbamate (700 mg, 1.61 mmol) in HCl (in MeOH, 6 N, 5 mL) was stirred at ambient temperature for 3 hours. The volatiles were removed under reduced pressure. The residue was dissolved in DMSO (3 mL). 6-chloronicotinonitrile (323 mg, 2.41 mmol), KI (10 mg, 0.06 mmol) and DIPEA (311 mg, 2.41 mmol) were then added. The reaction mixture was stirred at 120° C. for 14 h, cooled to ambient temperature, diluted with H2O (20 mL), and extracted with EtOAc (3×40 mL). The combined extracts were washed with brine (3×10 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by chromatography to give the title compound. MS (m/z): 436 (M+H)+.

Workup

  1. customThe volatiles were removed under reduced pressure
  2. dissolutionThe residue was dissolved in DMSO (3 mL)
  3. temperaturecooled to ambient temperature
  4. extractionextracted with EtOAc (3×40 mL)
  5. washThe combined extracts were washed with brine (3×10 mL)
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by chromatography

Sources & evidence

ORD record
ord-086b428846fd46a1919b34691a70c2ba
Source dataset
uspto-grants-2016_05
Patent number
US09346810B2

Reaction notes

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