5-Isocyanato-2-methylpyridine → (R)-benzyl 4-(2-fluoro-3-(3-(6-methylpyridin-3-yl)ureido)benzyl)-2-methylpiperazine-1-carboxylate

HRID 539721Notes

Reaction equation

HRID 539721 reaction equation
[NH2:1][C:2]1[C:3]([F:26])=[C:4]([CH:23]=[CH:24][CH:25]=1)[CH2:5][N:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])[C@H:8]([CH3:22])[CH2:7]1.[N:27]([C:30]1[CH:31]=[CH:32][C:33]([CH3:36])=[N:34][CH:35]=1)=[C:28]=[O:29]>C1COCC1>[F:26][C:3]1[C:2]([NH:1][C:28]([NH:27][C:30]2[CH:35]=[N:34][C:33]([CH3:36])=[CH:32][CH:31]=2)=[O:29])=[CH:25][CH:24]=[CH:23][C:4]=1[CH2:5][N:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])[C@H:8]([CH3:22])[CH2:7]1

Participants

4

Reactant 2

HCID 73305055-Isocyanato-2-methylpyridineHCID 58919233(R)-benzyl 4-(3-amino-2-fluorobenzyl)-2-methylpiperazine-1-carboxylate

Product 1

HCID 58919236(R)-benzyl 4-(2-fluoro-3-(3-(6-methylpyridin-3-yl)ureido)benzyl)-2-methylpiperazine-1-carboxylateYield 71%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a room temperature solution of (R)-benzyl 4-(3-amino-2-fluorobenzyl)-2-methylpiperazine-1-carboxylate (250 mg, 0.70 mmol, 1.0 equiv) in dry THF (3 mL) was added 5-isocyanato-2-methylpyridine (94 mg, 0.70 mmol, 1.0 equiv). After 1 h, the reaction was complete, as determined by LCMS. The reaction was washed with aq. satd. NaHCO3 and brine, dried over sodium sulfate, and concentrated in vacuo. Flash chromatography (2%-10% MeOH/DCM) provided (R)-benzyl 4-(2-fluoro-3-(3-(6-methylpyridin-3-yl)ureido)benzyl)-2-methylpiperazine-1-carboxylate (244 mg, 71%). LCMS m/z (APCI)=492.2 (M+H).

Workup

  1. washThe reaction was washed with aq. satd
  2. dry with materialNaHCO3 and brine, dried over sodium sulfate
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5919cfc412ec4dc48ac0e64f79d65f4b
Source dataset
uspto-grants-2014_10
Patent number
US08871768B2

Reaction notes

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