Benzyl chloroformate → HCID 88575710, compound

HRID 713699Notes

Reaction equation

HRID 713699 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([CH2:8][C:9]([N:11]([O:13][CH3:14])[CH3:12])=[O:10])[CH:5]=[CH:4][CH:3]=1.CCN([CH:21]([CH3:23])[CH3:22])C(C)C.Cl[C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26]>C(Cl)Cl>[CH2:28]([O:27][C:25](/[N:1]=[C:2]1/[N:7]([C:25]([O:27][CH2:28][C:22]2[CH:21]=[CH:23][CH:34]=[CH:29][CH:30]=2)=[O:26])[C:6]([CH2:8][C:9]([N:11]([O:13][CH3:14])[CH3:12])=[O:10])=[CH:5][CH:4]=[CH:3]/1)=[O:26])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

5

Reactant 3

HCID 10387Benzyl chloroformate2×HCID 81531DiisopropylethylamineHCID 87106433HCID 87106433, compound

Product 1

HCID 88575710HCID 88575710, compoundYield 122.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-(6-aminopyridin-2-yl) N-methoxy-N-methylacetamide (84.4 mg, 0.43 mmol) in DCM (15 ml) was added DIEA (0.114 ml, 0.65 mmol) and the resulting mixture cooled via ice/water bath to 0° C. Benzyl chloroformate (0.08 ml, 0.60 mmol) was added after 5 minutes and the resulting solution stirred for 1 hour allowing to warm to room temperature. The major product was observed to be the di-Cbz protected intermediate via LC-MS and TLC. Therefore, an additional 1 eq of benzyl chloroformate was added to ensure that all the product was converted to the di-CBz product. The reaction was quenched with water (10 ml) and extracted with DCM (2×10 mL). The organics were combined, washed with water (5 mL) and brine (5 mL), dried over sodium sulfated, filtered, and concentrated under reduced pressure. The residue was purified by preparative TLC plate (1000 μM) eluting with 25% ethyl acetate in hexane to afforded the title compound (170.4 mg, 85%). LC-MS: C25H25N3O6 calculated 463.48 found m/z (ES) 464 (MH)+ and 330 (M-Cbz)+.

Workup

  1. temperatureto warm to room temperature
  2. customThe reaction was quenched with water (10 ml)
  3. extractionextracted with DCM (2×10 mL)
  4. washwashed with water (5 mL) and brine (5 mL)
  5. dry with materialdried over sodium
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by preparative TLC plate (1000 μM)
  9. washeluting with 25% ethyl acetate in hexane

Sources & evidence

ORD record
ord-9d15a7f11a034461a1e17fc9b81debd1
Source dataset
uspto-grants-2015_11
Patent number
US09186354B2

Reaction notes

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