4-Methylmorpholine → HCID 18923219, compound

HRID 1900008Notes

Reaction equation

HRID 1900008 reaction equation
[C:1](Cl)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[C:8]([O:12][C:13]([N:15]1[CH2:22][CH2:21][CH2:20][C@H:16]1[C:17]([OH:19])=O)=[O:14])([CH3:11])([CH3:10])[CH3:9].[CH3:23]N1CCOCC1.[NH2:30][CH2:31][C:32]([N:34]([C:36]1[C:37]([Cl:56])=[C:38]([C:52]([Cl:55])=[CH:53][CH:54]=1)[CH2:39][O:40][C:41]1[C:42]2[N:43]([C:47]([Br:51])=[C:48]([CH3:50])[N:49]=2)[CH:44]=[CH:45][CH:46]=1)[CH3:35])=[O:33]>ClCCl>[Br:51][C:47]1[N:43]2[CH:44]=[CH:45][CH:46]=[C:41]([O:40][CH2:39][C:38]3[C:52]([Cl:55])=[CH:53][CH:54]=[C:36]([N:34]([C:32](=[O:33])[CH2:31][NH:30][C:17](=[O:19])[C@@H:16]4[CH2:20][CH2:21][CH2:22][N:15]4[C:13]([O:12][C:8]([CH3:9])([CH3:10])[CH3:11])=[O:14])[CH3:35])[C:37]=3[Cl:56])[C:42]2=[N:49][C:48]=1[CH3:50].[Br:51][C:47]1[N:43]2[CH:44]=[CH:45][CH:46]=[C:41]([O:40][CH2:39][C:38]3[C:52]([Cl:55])=[CH:53][CH:54]=[C:36]([NH:34][C:32](=[O:33])[CH2:31][N:30]([CH3:23])[C:1](=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3])[C:37]=3[Cl:56])[C:42]2=[N:49][C:48]=1[CH3:50]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62493Pivaloyl chlorideHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 10790603HCID 10790603, compound

Product 2

HCID 18923219HCID 18923219, compoundHCID 67626277HCID 67626277, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Pivaloyl chloride (0.04 ml) was added dropwise to a mixture of tert-butoxycarbonyl-L-proline (77 mg), N-methylmorpholine (0.04 ml) and dichloromethane (3 ml) under a dry ice-tetrachloromethane bath cooling. This mixture was stirred for 5 minutes under an ice-water bath cooling and cooled under a dry ice-tetrachloromethane bath cooling. To the mixture was added a solution of 8-[3-(N-glycyl-N-methylamino)-2,6-dichlorobenzyloxy]-3-bromo-2-methylimidazo[1,2-a]pyridine (139 mg) in dichloromethane (4 ml). The mixture was stirred for 30 minutes at ambient temperature and washed with saturated aqueous solution of sodium hydrogen carbonate and water. The organic layer was dried over magnesium sulfate and evaporated in vacuo. The residue was purified by preparative thin-layer chromatography (dichloromethane:methanol=19:1, V/V) to give 3-bromo-8-[3-[N-(tert-butoxycarbonyl-L-prolylglycyl)-N-methylamino]-2,6-dichlorobenzyloxy]-2-methylimidazo[1,2-a]pyridine (72 mg) (Compound A), and 3-bromo-8-[2,6-dichloro-3-(N-methyl-N-pivaloylglycylamino)benzyloxy]-2-methylimidazo[1,2-a]pyridine (93 mg) (Compound B).

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. temperaturecooled under a dry ice-tetrachloromethane bath
  4. temperaturecooling
  5. stirringThe mixture was stirred for 30 minutes at ambient temperature
  6. washwashed with saturated aqueous solution of sodium hydrogen carbonate and water
  7. dry with materialThe organic layer was dried over magnesium sulfate
  8. customevaporated in vacuo
  9. customThe residue was purified by preparative thin-layer chromatography (dichloromethane:methanol=19:1, V/V)

Sources & evidence

ORD record
ord-f59ebafdb5e64e108c62dc43a65dd356
Source dataset
uspto-grants-1996_11
Patent number
US05574042

Reaction notes

Loading…