Hydrochloric Acid → (R)-3-(1-(6-chloro-5-cyanopyrazin-2-yl)piperidin-3-yl)-1-methyl-1-phenylurea

HRID 1050623Notes

Reaction equation

HRID 1050623 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][CH2:11][C@@H:10]([NH:14][C:15](=[O:21])OC(C)(C)C)[CH2:9]2)[CH:5]=[N:4][C:3]=1[C:22]#[N:23].Cl.CCN(C(C)C)C(C)C.[CH3:34][N:35]([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)C(Cl)=O>O1CCOCC1.CCOC(C)=O>[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][CH2:11][C@@H:10]([NH:14][C:15](=[O:21])[N:35]([CH3:34])[C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[CH2:9]2)[CH:5]=[N:4][C:3]=1[C:22]#[N:23]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 77969Carbamic chloride, N-methyl-N-phenyl-HCID 81531DiisopropylethylamineHCID 118114972(R)-tert-butyl 1-(6-chloro-5-cyanopyrazin-2-yl)piperidin-3-ylcarbamate

Product 1

HCID 118115165(R)-3-(1-(6-chloro-5-cyanopyrazin-2-yl)piperidin-3-yl)-1-methyl-1-phenylureaYield 119.1%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

(R)-tert-Butyl 1-(6-chloro-5-cyanopyrazin-2-yl)piperidin-3-ylcarbamate (87, 400 mg, 1.20 mmol) was treated with 10 mL 4N HCl in dioxane for 2 hours. The mixture was concentrated in vacuo to dryness. It was dissolved in 3 mL DMF/15 mL dioxane. To it were added DIEA (2.09 mL, 12 mmol) and then N-methyl-N-phenylcarbamoyl chloride (610 mg, 3.6 mmol). The mixture was stirred for 3 hours, diluted with 100 mL EtOAc, washed with water ×3, dried, concentrated and subjected to flash column with 0 to 4% MeOH in DCM to isolate (R)-3-(1-(6-chloro-5-cyanopyrazin-2-yl)piperidin-3-yl)-1-methyl-1-phenylurea (513, 530 mg) in quantitative yield.

Workup

  1. concentrationThe mixture was concentrated in vacuo to dryness
  2. dissolutionIt was dissolved in 3 mL DMF/15 mL dioxane
  3. washwashed with water ×3
  4. customdried
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-48ffdcaf184546e99048b4ec40732f5f
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

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