1,2-Dichloroethane → HCID 58504584, compound

HRID 2367423Notes

Reaction equation

HRID 2367423 reaction equation
CC([N:5]([C@H:9]1[CH2:14][CH2:13][C@@H:12]([CH3:15])[N:11]([C:16]2[CH:21]=[C:20]([C:22]3[CH:27]=[CH:26][C:25]([C:28]#[N:29])=[C:24]([F:30])[CH:23]=3)[N:19]=[C:18]([NH2:31])[N:17]=2)[CH2:10]1)[C:6](=O)[O-:7])(C)C.Cl.C(O)(=O)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1>O1CCOCC1.CN(C=O)C.O>[NH2:31][C:18]1[N:17]=[C:16]([N:11]2[C@H:12]([CH3:15])[CH2:13][CH2:14][C@H:9]([NH:5][C:6](=[O:7])[C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH2:10]2)[CH:21]=[C:20]([C:22]2[CH:27]=[CH:26][C:25]([C:28]#[N:29])=[C:24]([F:30])[CH:23]=2)[N:19]=1

Participants

10

Reactant 6

HCID 111,2-DichloroethaneHCID 243Benzoic AcidHCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 86659190HCID 86659190, compound

Product 1

HCID 58504584HCID 58504584, compoundYield 29.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Procedure

To 1,1-dimethylethyl{(3S,6R)-1-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-6-methyl-3-piperidinyl}carbamate (100 mg, 0.234 mmol) in a 20 mL vial was added 2 mL of 4M HCl in 1,4-dioxane, and the solution was stirred at room temperature for 30 minutes. The reaction was then concentrated. To the resulting whitish solid was added a premixed solution of benzoic acid (34.4 mg, 0.281 mmol), EDC (67.4 mg, 0.352 mmol), HOBT (71.8 mg, 0.469 mmol), and N-methylmorpholine (0.129 mL, 1.172 mmol) in DMF (2 mL), and the resulting solution was stirred at room temperature overnight. The reaction was diluted with water (10 mL), then extracted with EtOAc (3×10 mL). The organics were combined, washed with brine, then dried over MgSO4, filtered and concentrated to afford the crude title compound (30 mg) as a yellow oil. LC-MS (ES) m/z=431 [M+H]+.

Workup

  1. concentrationThe reaction was then concentrated
  2. stirringthe resulting solution was stirred at room temperature overnight
  3. extractionextracted with EtOAc (3×10 mL)
  4. washwashed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-6143d2ab4886453db92cf08104f26300
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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