Methyl chloroformate → Methyl {(1R)-1-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-[2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-1-oxo-2,8-diazaspiro[4.5]dec-8-yl]ethyl}carbamate

HRID 1848545Notes

Reaction equation

HRID 1848545 reaction equation
[NH2:1][C@H:2]([C:22]1[C:23]([CH3:32])=[C:24]2[C:28](=[CH:29][CH:30]=1)[C:27](=[O:31])[O:26][CH2:25]2)[CH2:3][N:4]1[CH2:21][CH2:20][C:7]2([C:11](=[O:12])[N:10]([C:13]3[CH2:14][O:15][C:16](=[O:19])[C:17]=3[CH3:18])[CH2:9][CH2:8]2)[CH2:6][CH2:5]1.C(N(CC)CC)C.Cl[C:41]([O:43][CH3:44])=[O:42]>ClCCl>[CH3:32][C:23]1[C:24]2[CH2:25][O:26][C:27](=[O:31])[C:28]=2[CH:29]=[CH:30][C:22]=1[C@@H:2]([NH:1][C:41](=[O:42])[O:43][CH3:44])[CH2:3][N:4]1[CH2:5][CH2:6][C:7]2([C:11](=[O:12])[N:10]([C:13]3[CH2:14][O:15][C:16](=[O:19])[C:17]=3[CH3:18])[CH2:9][CH2:8]2)[CH2:20][CH2:21]1

Participants

5

Reactant 3

HCID 6586Methyl chloroformate2×HCID 8471Triethylamine2×HCID 72948650(R)-8-(2-amino-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one

Product 1

HCID 72948651Methyl {(1R)-1-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-[2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-1-oxo-2,8-diazaspiro[4.5]dec-8-yl]ethyl}carbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-8-(2-amino-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one (Example 62) (35 mg, 0.08 mmol) and triethylamine (17 μL, 0.12 mmol) in dichloromethane (2 mL) was added methyl chloroformate (11 mg, 0.12 mmol) at 0° C. under nitrogen atmosphere. The reaction mixture was allowed to warm to room temperature and stir for 2 h. TLC indicated half of starting material remained. The reaction mixture was re-cooled to 0° C. and triethylamine (17 μL, 0.12 mmol) was added thereto, followed by methyl chloroformate (11 mg, 0.12 mmol). The reaction mixture was allowed to warm to room temperature and stirred for another 2 h. TLC showed the reaction was complete. The resulting mixture was concentrated in vacuo. The residue was taken up into small amount of DCM and purified by preparative TLC (dichloromethane:methanol=15:1) to afford the title compound. MS-ESI (m/z): 498 (M+1)+.

Workup

  1. temperatureThe reaction mixture was re-cooled to 0° C.
  2. temperatureto warm to room temperature
  3. stirringstirred for another 2 h
  4. concentrationThe resulting mixture was concentrated in vacuo
  5. custompurified by preparative TLC (dichloromethane:methanol=15:1)

Sources & evidence

ORD record
ord-82d1557aed5d448398bf48c0341b747c
Source dataset
uspto-grants-2015_02
Patent number
US08952166B2

Reaction notes

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