Methylamine → HCID 178485719, compound

HRID 1063653Notes

Reaction equation

HRID 1063653 reaction equation
[Cl:1][C:2]1[CH:29]=[CH:28][C:5]([O:6][C:7]([N:9]([CH3:27])[CH2:10][CH2:11][C@H:12]2[CH2:17][CH2:16][C@H:15]([C:18]([N:20]([CH3:26])[CH2:21][CH2:22][C:23]([OH:25])=O)=[O:19])[CH2:14][CH2:13]2)=[O:8])=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[CH3:36][NH2:37]>C(Cl)Cl.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][C:7](=[O:8])[N:9]([CH3:27])[CH2:10][CH2:11][C@H:12]2[CH2:17][CH2:16][C@H:15]([C:18](=[O:19])[N:20]([CH3:26])[CH2:21][CH2:22][C:23](=[O:25])[NH:37][CH3:36])[CH2:14][CH2:13]2)=[CH:28][CH:29]=1

Participants

6

Reactant 3

HCID 6329MethylamineHCID 65578Oxalyl chlorideHCID 178483653HCID 178483653, compound

Product 1

HCID 178485719HCID 178485719, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A solution of 0.088 g (0.20 mmol) of trans-3-[(4-{2-[(4-chloro-phenoxycarbonyl)-methyl-amino]-ethyl}-cyclohexanecarbonyl)-methyl-amino]-propionic acid in 2 mL of CH2Cl2 was treated at RT with 1 drop of DMF, followed by 0.019 mL (0.22 mmol, 1.1 eq) of oxalyl chloride and stirring was continued for 90 min. The solvent was evaporated, the residue was redissolved in 2.5 mL of CH2Cl2 and added to a solution of 0.25 mL (2.00 mmol, 10 eq) of methylamine (33% solution in EtOH) in 2 mL of CH2Cl2 at 0° C. The reaction mixture was stirred at 0° C. for 3/4 h, then partitioned between Et2O (×3)/aqueous 10% KHSO4. The organic phases were washed once with aqueous 10% NaCl, dried over Na2SO4 and evaporated. Purification by flash-chromatography on 20 g silica gel (CH2Cl2:MeOH 98:2 to 95:5) gave 0.042 g (48%) of pure trans-methyl-(2-{4-[methyl-(2-methylcarbamoyl-ethyl)-carbamoyl]-cyclohexyl}-ethyl)-carbamic acid 4-chloro-phenyl ester, MS: 438 (MH+, 1Cl).

Workup

  1. customThe solvent was evaporated
  2. dissolutionthe residue was redissolved in 2.5 mL of CH2Cl2
  3. stirringThe reaction mixture was stirred at 0° C. for 3/4 h
  4. custompartitioned between Et2O (×3)/aqueous 10% KHSO4
  5. washThe organic phases were washed once with aqueous 10% NaCl
  6. dry with materialdried over Na2SO4
  7. customevaporated
  8. customPurification by flash-chromatography on 20 g silica gel (CH2Cl2:MeOH 98:2 to 95:5)

Sources & evidence

ORD record
ord-cfcd2e3713d84708812f5a7e605fff0d
Source dataset
uspto-grants-2005_11
Patent number
US06965048B2

Reaction notes

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