1,2-Dichloroethane → HCID 86659193, compound

HRID 2367429Notes

Reaction equation

HRID 2367429 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](S(C)(=O)=O)[N:5]=[C:4]([N:12]2[C@H:17]([C:18]([F:21])([F:20])[F:19])[CH2:16][CH2:15][C@H:14]([C:22]([OH:24])=O)[CH2:13]2)[CH:3]=1.C[CH2:26][N:27](C(C)C)C(C)C.CN.C1[CH:37]=[CH:38][C:39]2[N:44](O)N=N[C:40]=2[CH:41]=1.C(Cl)CCl.CN1CCOCC1.C1(N)CCCC1>O1CCOCC1.C1COCC1.O>[Cl:1][C:2]1[N:7]=[C:6]([NH:27][CH3:26])[N:5]=[C:4]([N:12]2[C@H:17]([C:18]([F:19])([F:20])[F:21])[CH2:16][CH2:15][C@H:14]([C:22]([NH:44][CH:39]3[CH2:38][CH2:37][CH2:41][CH2:40]3)=[O:24])[CH2:13]2)[CH:3]=1

Participants

11

Reactant 7

HCID 111,2-DichloroethaneHCID 2906CyclopentylamineHCID 6329Methylamine2×HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 86659192HCID 86659192, compound

Product 1

HCID 86659193HCID 86659193, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

Into a 20 mL vial, cis-1-[6-chloro-2-(methylsulfonyl)-4-pyrimidinyl]-6-(trifluoromethyl)-3-piperidinecarboxylic acid (77 mg, 0.199 mmol) was dissolved in 1,4-dioxane (1 mL), and Hunig's base was added (0.14 mL, 0.794 mmol) followed by methylamine (0.199 mL, 0.397 mmol). The reaction mixture was stirred at room temperature overnight. Additional 100 uL of 2M methylamine in THF were added, and the reaction mixture was stirred at room temperature until LCMS analysis indicates>95% completion. The reaction was concentrated, then re-dissolved with DMF (2 mL), and added HOBT (60.8 mg, 0.397 mmol), EDC (57.1 mg, 0.298 mmol), N-methylmorpholine (0.109 mL, 0.993 mmol) and cyclopentylamine (0.029 mL, 0.298 mmol). The reaction was stirred at room temperature overnight. Water (15 mL) was added, and the resulting mixture was extracted with EtOAc (3×10 mL). The organics were combined, washed with brine, dried (MgSO4), filtered, and concentrated. The resulting material was dissolved in 1 mL DMSO and purified on HPLC (HPLC condition: open-access Gilson using Unipoint software with a Varian Polaris 5u C18(2) 100A, 50×30.00 mm 5 micron. 10-minute run (30 ml/min, 40% CH3CN/H2O, 0.1% TFA to 60% CH3CN/H2O, 0.1% TFA) with UV detection at 254 nm). Product fractions were pooled and concentrated and freeze-dried to afford the title compound (40 mg) as a white solid. LC-MS (ES) m/z=406 [M+H]+.

Workup

  1. stirringthe reaction mixture was stirred at room temperature until LCMS analysis
  2. concentrationThe reaction was concentrated
  3. dissolutionre-dissolved with DMF (2 mL)
  4. stirringThe reaction was stirred at room temperature overnight
  5. extractionthe resulting mixture was extracted with EtOAc (3×10 mL)
  6. washwashed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. dissolutionThe resulting material was dissolved in 1 mL DMSO
  11. custompurified on HPLC (HPLC condition
  12. custom10-minute
  13. concentrationconcentrated
  14. customfreeze-dried

Sources & evidence

ORD record
ord-927f604f73a042638aaa4e12fcfb5441
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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