Hydrochloric Acid → (4-(4-(2-chloropyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(isoxazol-5-ylcarbonyl)piperidin-4-yl)acetonitrile

HRID 1876847Notes

Reaction equation

HRID 1876847 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[N:10][N:11]([C:13]3([CH2:26][C:27]#[N:28])[CH2:18][CH2:17][N:16]([C:19]([O:21]C(C)(C)C)=O)[CH2:15][CH2:14]3)[CH:12]=2)[CH:5]=[CH:4][N:3]=1.Cl.C(N(CC)CC)C.[O:37]1[C:41](C(Cl)=O)=[CH:40][CH:39]=[N:38]1>O1CCOCC1.C(Cl)Cl>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[N:10][N:11]([C:13]3([CH2:26][C:27]#[N:28])[CH2:18][CH2:17][N:16]([C:19]([C:41]4[O:37][N:38]=[CH:39][CH:40]=4)=[O:21])[CH2:15][CH2:14]3)[CH:12]=2)[CH:5]=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric Acid2×HCID 8471TriethylamineHCID 2736707Isoxazole-5-carbonyl chlorideHCID 86637283tert-butyl 4-(4-(2-chloropyrimidin-4-yl)-1H-pyrazol-1-yl)-4-(cyanomethyl)piperidine-1-carboxylate

Product 1

HCID 86637284(4-(4-(2-chloropyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(isoxazol-5-ylcarbonyl)piperidin-4-yl)acetonitrile

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent2×

Procedure

To a mixture of tert-butyl 4-(4-(2-chloropyrimidin-4-yl)-1H-pyrazol-1-yl)-4-(cyanomethyl)piperidine-1-carboxylate (0.259 g, 0.643 mmol) in 2 mL of dioxane was added 4 M HCl in dioxane (4.0 mL). The reaction was stirred at room temperature for 30 min, then evaporated to dryness. To the resulting crude HCl salt in methylene chloride (5.0 mL) was added triethylamine (0.269 mL, 1.93 mmol) followed by isoxazole-5-carbonyl chloride (0.0744 mL, 0.771 mmol). The mixture was stirred at room temperature for 30 min, washed with saturated sodium bicarbonate, dried, and evaporated to dryness. The residue was used directly in next step (233 mg, 91%). LCMS (M+H) 398.0.

Workup

  1. customevaporated to dryness
  2. stirringThe mixture was stirred at room temperature for 30 min
  3. washwashed with saturated sodium bicarbonate
  4. customdried
  5. customevaporated to dryness

Sources & evidence

ORD record
ord-ddb2244734f849fabb91952d17403aef
Source dataset
uspto-grants-2012_11
Patent number
US08309718B2

Reaction notes

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