Methyl chloroformate → HCID 24890786, compound

HRID 39343Notes

Reaction equation

HRID 39343 reaction equation
[CH:1]1([N:6]2[C:15]3[N:14]=[C:13]([NH2:16])[N:12]=[CH:11][C:10]=3[N:9]3[CH:17]=[N:18][N:19]=[C:8]3[C@H:7]2[CH2:20][CH3:21])[CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].ClC(OC)=O.[Cl-].[NH4+:30]>CN(C=O)C>[CH:1]1([N:6]2[C:15]3[N:14]=[C:13]([NH:16][C:2]4[CH:3]=[N:30][CH:4]=[CH:5][CH:1]=4)[N:12]=[CH:11][C:10]=3[N:9]3[CH:17]=[N:18][N:19]=[C:8]3[C@H:7]2[CH2:20][CH3:21])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

6

Reactant 4

HCID 6586Methyl chloroformateHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 24890788HCID 24890788, compound

Product 1

HCID 24890786HCID 24890786, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To (R)-5-cyclopentyl-4-ethyl-4,5-dihydro-[1,2,4]triazolo[4,3-f]pteridin-7-amine (50 mg, 0.175 mmol) in DMF (1 ml) at 0° C. was added sodium hydride (60% in mineral oil, 7.7 mg, 0.193 mmol). The reaction mixture was stirred for 10 minutes, then methyl chloroformate (13.6 μL, 0.175 mmol) was added. The reaction was allowed to warm up to room temperature and was stirred for 18 hours. Ammonium chloride (5 ml, sat. aq. soln.) was added and extracted with EtOAc (3×10 ml). The combined organics were washed with brine (10 ml), dried over MgSO4, filtered and the solvent removed under vacuum. The crude product was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 M, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min] to afford the title compound as an off-white powder (25 mg, 31%).

Workup

  1. stirringwas stirred for 18 hours
  2. extractionextracted with EtOAc (3×10 ml)
  3. washThe combined organics were washed with brine (10 ml)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customthe solvent removed under vacuum
  7. customThe crude product was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 M, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]

Sources & evidence

ORD record
ord-4a4138a7f7ee4c84b8918cd380cea8f8
Source dataset
uspto-grants-2013_09
Patent number
US08524902B2

Reaction notes

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