Tetrahydrofuran → HCID 70571586, compound

HRID 2403591Notes

Reaction equation

HRID 2403591 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]([N:12]([CH2:14][C:15]1[CH:16]=[C:17]([C:21]2[CH:22]=[N:23][C:24]([N:27]3[CH2:32][CH2:31][N:30]([C:33]4[C:41]([Cl:42])=[CH:40][C:36]([C:37](O)=[O:38])=[CH:35][N:34]=4)[CH2:29][CH2:28]3)=[N:25][CH:26]=2)[CH:18]=[CH:19][CH:20]=1)[CH3:13])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1COCC1.C(Cl)(=O)OCC(C)C.[BH4-].[Na+]>O>[Cl:42][C:41]1[C:33]([N:30]2[CH2:29][CH2:28][N:27]([C:24]3[N:23]=[CH:22][C:21]([C:17]4[CH:16]=[C:15]([CH:20]=[CH:19][CH:18]=4)[CH2:14][N:12]([CH3:13])[C:10](=[O:11])[CH2:9][NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[CH:26][N:25]=3)[CH2:32][CH2:31]2)=[N:34][CH:35]=[C:36]([CH2:37][OH:38])[CH:40]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 62365Isobutyl chloroformateHCID 4311764Sodium borohydrideHCID 68106169HCID 68106169, compound

Product 1

HCID 70571586HCID 70571586, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
-78 °C

Procedure

Under ice-cooling, 6-(4-{5-[3-({[N-(tert-butoxycarbonyl)glycyl](methyl)amino}methyl)phenyl]pyrimidin-2-yl}piperazin-1-yl)-5-chloronicotinic acid (303 mg), THF (9 ml), and TEA (65 mg) were mixed, and isobutyl chlorocarbonate (77 mg) was added thereto, followed by stirring at the same temperature for 1.5 hours. The reaction mixture was cooled to −78° C., and a solution of sodium borohydride (77 mg) in water (1.1 ml) was added thereto, followed by warming to 0° C. and stirring for 30 minutes. To the reaction mixture was added water, followed by extraction with EtOAc, and the organic layer was washed with water and saturated brine, and dried over Na2SO4. Under reduced pressure, the solvent was evaporated, and the obtained residue was purified by silica gel column chromatography (NH silica) to obtain tert-butyl (2-{[3-(2-{4-[3-chloro-5-(hydroxymethyl)pyridin-2-yl]piperazin-1-yl}pyrimidin-5-yl)benzyl](methyl)amino}-2-oxoethyl)carbamate (296 mg).

Workup

  1. temperatureUnder ice-cooling
  2. temperatureby warming to 0° C.
  3. stirringstirring for 30 minutes
  4. extractionfollowed by extraction with EtOAc
  5. washthe organic layer was washed with water and saturated brine
  6. dry with materialdried over Na2SO4
  7. customUnder reduced pressure, the solvent was evaporated
  8. customthe obtained residue was purified by silica gel column chromatography (NH silica)

Sources & evidence

ORD record
ord-9ffe520b6a524aacb9dff0d213e29915
Source dataset
uspto-grants-2014_08
Patent number
US08802679B2

Reaction notes

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