1,8-Diazabicyclo(5.4.0)undec-7-ene → 2-(2-(4-(7-chloroimidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)spiro[3.3]heptan-2-yl)acetonitrile

HRID 1853089Notes

Reaction equation

HRID 1853089 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[N:10][NH:11][CH:12]=2)[N:5]2[CH:13]=[CH:14][N:15]=[C:4]2[CH:3]=1.[CH2:16]1[C:19]2([CH2:22][CH2:21][CH2:20]2)[CH2:18][C:17]1=[CH:23][C:24]#[N:25].C1CCN2C(=NCCC2)CC1>CC#N>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[CH:12]=[N:11][N:10]([C:17]3([CH2:23][C:24]#[N:25])[CH2:18][C:19]4([CH2:22][CH2:21][CH2:20]4)[CH2:16]3)[CH:9]=2)[N:5]2[CH:13]=[CH:14][N:15]=[C:4]2[CH:3]=1

Participants

5

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 674519072-(Spiro[3.3]heptan-2-ylidene)acetonitrileHCID 866853027-chloro-5-(1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine

Product 1

HCID 866853442-(2-(4-(7-chloroimidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)spiro[3.3]heptan-2-yl)acetonitrileYield 81%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

7-Chloro-5-(1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine (Preparation M, Step A; 0.380 g, 1.73 mmol), 2-(spiro[3.3]heptan-2-ylidene)acetonitrile (Example 160, Steps A-C, 0.461 g, 3.46 mmol) and DBU (0.130 mL, 0.865 mmol) were suspended in MeCN (10 mL) and stirred at ambient temperature overnight. The reaction mixture was partitioned between saturated aqueous NH4Cl and EtOAc. The organic layer was washed with brine, dried (MgSO4), filtered concentrated under reduced pressure to afford the crude material, which was purified by flash column chromatography, eluting with 2-3% (9:1 MeOH:NH4OH)/DCM to provide 2-(2-(4-(7-chloroimidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)spiro[3.3]heptan-2-yl)acetonitrile (0.493 g, 1.40 mmol, 81% yield). MS (apci) m/z=353.1 (M+H).

Workup

  1. customThe reaction mixture was partitioned between saturated aqueous NH4Cl and EtOAc
  2. washThe organic layer was washed with brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto afford the crude material, which
  7. customwas purified by flash column chromatography
  8. washeluting with 2-3% (9:1 MeOH:NH4OH)/DCM

Sources & evidence

ORD record
ord-bdd883d20f9340fb88cc16e1f82e3313
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

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