Ethyl chloroformate → HCID 86705398, compound

HRID 926130Notes

Reaction equation

HRID 926130 reaction equation
[H-].[Na+].[NH2:3][C:4]1[N:11]=[CH:10][C:9]([CH2:12][N:13]2[CH2:18][C@@H:17]([CH3:19])[O:16][C@@H:15]([CH3:20])[CH2:14]2)=[CH:8][C:5]=1[C:6]#[N:7].Cl[C:22]([O:24][CH2:25][CH3:26])=[O:23].C(=O)(O)[O-].[Na+]>C1COCC1>[C:6]([C:5]1[C:4]([NH:3][C:22](=[O:23])[O:24][CH2:25][CH3:26])=[N:11][CH:10]=[C:9]([CH2:12][N:13]2[CH2:14][C@@H:15]([CH3:20])[O:16][C@@H:17]([CH3:19])[CH2:18]2)[CH:8]=1)#[N:7]

Participants

6

Reactant 4

HCID 10928Ethyl chloroformateHCID 24758Sodium hydride2×HCID 516892Sodium BicarbonateHCID 86705399HCID 86705399, compound

Product 1

HCID 86705398HCID 86705398, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride in mineral oil (60%, 25 mg, 0.61 mmol) was added to 2-amino-5-(((2S,6R)-2,6-dimethylmorpholino)methyl)nicotinonitrile (100 mg, 0.41 mmol) in THF (2 mL) and the mixture was stirred for 5 minutes. Ethyl chloroformate (0.05 mL, 0.48 mmol) was added followed by additional sodium hydride (16 mg, 0.41 mmol) and the reaction stirred at room temperature for 3 h. The reaction was poured into a saturated solution of sodium bicarbonate (10 mL), extracted with EtOAc (3×5 mL), dried (Na2SO4) and concentrated under reduced pressure. The residue was taken up in methanol (10 mL) and stirred with potassium carbonate (170 mg) for 10 minutes, then poured into saturated sodium bicarbonate (10 mL) and extracted with EtOAc (3×5 mL). The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure. Purification (FCC, SiO2, 0-100%, EtOAc/hexanes) afforded the title compound as a white powder (104 mg, 80%). 1H NMR (400 MHz, DMSO-d6) δ 1.04 (d, J=6.27 Hz, 6H), 1.26 (t, J=7.03 Hz, 3H), 1.69 (t, J=10.60 Hz, 2H), 2.67 (d, J=10.67 Hz, 2H), 3.51 (s, 2H), 3.54-3.62 (m, 2H), 4.17 (q, J=7.11 Hz, 2H), 8.12-8.24 (m, 1H), 8.56 (d, J=2.01 Hz, 1H), 10.37 (s, 1H).

Workup

  1. stirringthe reaction stirred at room temperature for 3 h
  2. extractionextracted with EtOAc (3×5 mL)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated under reduced pressure
  5. stirringstirred with potassium carbonate (170 mg) for 10 minutes
  6. additionpoured into saturated sodium bicarbonate (10 mL)
  7. extractionextracted with EtOAc (3×5 mL)
  8. dry with materialThe combined organic layers were dried (Na2SO4)
  9. concentrationconcentrated under reduced pressure
  10. customPurification (FCC, SiO2, 0-100%, EtOAc/hexanes)

Sources & evidence

ORD record
ord-9627ce2192204560acd26e92250efa2c
Source dataset
uspto-grants-2016_03
Patent number
US09284335B2

Reaction notes

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