Methyl chloroformate → (R)-methyl 4-(2-fluoro-3-(3-(2-methylpyridin-4-yl)ureido)benzyl)-2-methylpiperazine-1-carboxylate

HRID 539724Notes

Reaction equation

HRID 539724 reaction equation
[F:1][C:2]1[C:25]([NH:26][C:27]([NH:29][C:30]2[CH:35]=[C:34]([CH3:36])[N:33]=[CH:32][CH:31]=2)=[O:28])=[CH:24][CH:23]=[CH:22][C:3]=1[CH2:4][N:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][CH2:14]C2C=CC=CC=2)=[O:12])[C@H:7]([CH3:21])[CH2:6]1.CCN(CC)CC.ClC(OC)=O>CO.[Pd]>[F:1][C:2]1[C:25]([NH:26][C:27]([NH:29][C:30]2[CH:31]=[CH:32][N:33]=[C:34]([CH3:36])[CH:35]=2)=[O:28])=[CH:24][CH:23]=[CH:22][C:3]=1[CH2:4][N:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][CH3:14])=[O:12])[C@H:7]([CH3:21])[CH2:6]1

Participants

6

Reactant 3

HCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 58919234(R)-benzyl 4-(2-fluoro-3-(3-(2-methylpyridin-4-yl)ureido)benzyl)-2-methylpiperazine-1-carboxylate

Product 1

HCID 58919235(R)-methyl 4-(2-fluoro-3-(3-(2-methylpyridin-4-yl)ureido)benzyl)-2-methylpiperazine-1-carboxylateYield 53%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of (R)-benzyl 4-(2-fluoro-3-(3-(6-methylpyridin-4-yl)ureido)benzyl)-2-methylpiperazine-1-carboxylate (190 mg, 0.39 mmol, 1.0 equiv) in MeOH (20 mL) was added 10% Pd/C (approx. 100 mg). The resulting suspension was stirred and sparged with hydrogen gas using a balloon and needle. After 1 h, reaction was complete, as determined by LCMS. The mixture was filtered through a pad of Celite, and the celite pad was washed with additional methanol. The mixture was concentrated in vacuo, and the resulting residue was dissolved in dry DCM (10 mL). To this room temperature solution was added Et3N (167 uL, 1.2 mmol, 3.0 equiv), followed by the addition of methyl chloroformate (46 uL, 0.60 mmol, 1.5 equiv) by syringe. After 10 minutes the reaction mixture was quenched by the addition of methanol. The solvent was removed in vacuo, and the mixture was purified by preparative TLC (0.5% Et3N/7% MeOH/92.5% DCM) to provide (R)-methyl 4-(2-fluoro-3-(3-(2-methylpyridin-4-yl)ureido)benzyl)-2-methylpiperazine-1-carboxylate (85.9 mg, 50%). LCMS m/z (APCI)=416.3 (M+H).

Workup

  1. customsparged with hydrogen gas
  2. customreaction
  3. filtrationThe mixture was filtered through a pad of Celite
  4. washthe celite pad was washed with additional methanol
  5. concentrationThe mixture was concentrated in vacuo
  6. dissolutionthe resulting residue was dissolved in dry DCM (10 mL)
  7. customAfter 10 minutes the reaction mixture was quenched by the addition of methanol
  8. customThe solvent was removed in vacuo
  9. customthe mixture was purified by preparative TLC (0.5% Et3N/7% MeOH/92.5% DCM)

Sources & evidence

ORD record
ord-d890c20292eb4cf796e17e60296ae22b
Source dataset
uspto-grants-2014_10
Patent number
US08871768B2

Reaction notes

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