Methyl chloroformate → HCID 178502276, compound

HRID 535743Notes

Reaction equation

HRID 535743 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([CH:18]2[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]([NH2:17])[CH3:16])[N:8]=1.C1COCC1.O.C([O-])(O)=O.[Na+].Cl[C:33]([O:35][CH3:36])=[O:34]>O>[Br:1][C:2]1[N:3]=[C:4]([CH:18]2[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 chloroformateHCID 516892Sodium BicarbonateHCID 21881883Oxolane--water (1/1)HCID 178462031HCID 178462031, compound

Product 1

HCID 178502276HCID 178502276, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of (S)—N1-(4-(4-bromo-2-cyclopropyl-1H-imidazol-5-yl)pyrimidin-2-yl)propane-1,2-diamine (13.3 g, 27.3 mmol, assumed theoretical yield) in 1:1 THF-water (200 mL) was cooled to 0° C. and solid NaHCO3 (20.6 g, 245 mmol) was added in portions. Methyl chloroformate (3.74 mL, 27.3 mmol) was added dropwise over 20 minutes and stirred for an additional 30 minutes. LCMS of an aliquot indicated complete reaction. Water (300 mL) was added and the resulting mixture was extracted with EtOAc (3×500 mL). The EtOAc layer was washed with brine (2×1 L), dried (Na2SO4) and concentrated. The resulting solid was suspended in a mixture of EtOAc (7 mL) and ethyl ether (25 mL) and the resulting suspension was allowed to settle at 0° C. The solids were collected and washed with cold Et2O (20 mL) to afford (S)-methyl 1-(4-(4-bromo-2-cyclopropyl-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate (9.56 g, 24.1 mmol, 89%) as an off-white solid: LCMS (m/z) 395.1 (MH+), tR=0.61 minute; 1H NMR (400 MHz, CDCl3) δ 0.91-1.03 (m, 2H), 1.08-1.19 (m, 2H), 1.22 (d, J=6.6 Hz, 3H), 1.77 (br s, 1H), 2.13-2.26 (m, 1H), 2.70-2.90 (m, 1H), 3.70 (s, 3H), 3.90-4.03 (m, 1H), 4.18-4.32 (m, 1H), 4.46-4.86 (m, 1H), 5.48-5.60 (m, 1H), 7.46 (d, J=5.5 Hz, 1H), 8.24 (d, J=5.4 Hz, 1H).

Workup

  1. customreaction
  2. extractionthe resulting mixture was extracted with EtOAc (3×500 mL)
  3. washThe EtOAc layer was washed with brine (2×1 L)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. additionThe resulting solid was suspended in a mixture of EtOAc (7 mL) and ethyl ether (25 mL)
  7. customto settle at 0° C
  8. customThe solids were collected
  9. washwashed with cold Et2O (20 mL)

Sources & evidence

ORD record
ord-988af0f4c29a42a5ab2e7fd78eb5555e
Source dataset
uspto-grants-2014_10
Patent number
US08859548B2

Reaction notes

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