Methyl chloroformate → HCID 178502278, compound

HRID 1043737Notes

Reaction equation

HRID 1043737 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([CH:18]2[CH2:21][CH2:20][CH2:19]2)[NH:5][C:6]=1[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH2:14][CH:15]([NH2:17])[CH3:16])[N:8]=1.C([O-])(O)=O.[Na+].C1COCC1.Cl[C:33]([O:35][CH3:36])=[O:34]>C1COCC1.O>[Br:1][C:2]1[N:3]=[C:4]([CH:18]2[CH2:21][CH2:20][CH2:19]2)[NH:5][C:6]=1[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH2:14][C@@H:15]([NH:17][C:33](=[O:34])[O:35][CH3:36])[CH3:16])[N:8]=1

Participants

6

Reactant 4

HCID 6586Methyl chloroformate2×HCID 8028TetrahydrofuranHCID 516892Sodium Bicarbonate2×HCID 178464560HCID 178464560, compound

Product 1

HCID 178502278HCID 178502278, compoundYield 108%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

A solution of S)—N1-(4-(4-bromo-2-cyclobutyl-1H-imidazol-5-yl)pyrimidin-2-yl)propane-1,2-diamine (0.25 g, 0.72 mmol) in THF-water (1:1, 8 mL) was cooled to 0° C. and then solid NaHCO3 (0.10 g, 1.2 mmol) was added with concomitant frothing. After 5 minutes, a THF solution of methyl chloroformate (0.1 M in THF, 4.3 mL, 0.43 mmol) was added dropwise to the mixture and the reaction was maintained overnight allowing the cooling bath to expire. LCMS indicate incomplete reaction and addition methyl chloroformate solution and NaHCO3 was added. After the reaction was deemed complete by LCMS, the reaction mixture was extracted with EtOAc. The organic phase was washed with brine and dried (Na2SO4), and concentrated to give (S)-methyl 1-(4-(4-bromo-2-cyclobutyl-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate as a yellow solid (0.19 g): LCMS (m/z) 409.0 (MH+), tR=0.63 minute.

Workup

  1. temperaturethe reaction was maintained overnight
  2. additionwas added
  3. extractionthe reaction mixture was extracted with EtOAc
  4. washThe organic phase was washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-dff3086c5ae540069349d9d2786c6539
Source dataset
uspto-grants-2013_10
Patent number
US08563553B2

Reaction notes

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