(S)-(4-(3,4-Dichlorobenzyl)morpholin-2-YL)methanamine → N-[[(2S)-4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-2-(5-methyl-2-pyridin-3-yl-1,3-oxazol-4-yl)acetamide;formic acid

HRID 2212023Notes

Reaction equation

HRID 2212023 reaction equation
[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=2)=[N:4][C:3]=1[CH2:13][C:14]([OH:16])=[O:15].[Cl:17][C:18]1[CH:19]=[C:20]([CH:30]=[CH:31][C:32]=1[Cl:33])[CH2:21][N:22]1[CH2:27][CH2:26][O:25][C@@H:24]([CH2:28][NH2:29])[CH2:23]1>>[CH:14]([OH:16])=[O:15].[Cl:17][C:18]1[CH:19]=[C:20]([CH:30]=[CH:31][C:32]=1[Cl:33])[CH2:21][N:22]1[CH2:27][CH2:26][O:25][C@@H:24]([CH2:28][NH:29][C:14](=[O:16])[CH2:13][C:3]2[N:4]=[C:5]([C:7]3[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=3)[O:6][C:2]=2[CH3:1])[CH2:23]1

Participants

3

Reactant 2

HCID 10171585(S)-(4-(3,4-Dichlorobenzyl)morpholin-2-YL)methanamineHCID 21962835(5-Methyl-2-pyridin-3-yl-1,3-oxazol-4-yl)acetic acid

Product 1

HCID 86604281N-[[(2S)-4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-2-(5-methyl-2-pyridin-3-yl-1,3-oxazol-4-yl)acetamide;formic acidYield 209.3%

Conditions

Temperature
22 °C

Procedure

N,N′-carbonyldiimidazole (15 mg) was added to a stirred solution of Intermediate 34 (20 mg) at 22° C. under nitrogen, and the mixture was stirred at 22° C. for 1 h. Intermediate 9 (26 mg) was added and the mixture stirred at 22° C. for 24 h. The mixture was applied directly to a sulphonic acid ion exchange cartridge (Isolute SCX, 2 g) and eluted with methanol followed by 10% 0.880 ammonia in methanol. Evaporation of the methanolic ammonia fraction gave a gum (50 mg) which was further purified by solid phase extraction on silica gel (1 g Varian Bondelut cartridge), eluting with chloroform, ether, ethyl acetate, acetone and methanol to give a gum (38 mg). The gum was partitioned between dichloromethane and water, and the organic layer treated with polystyrene methylisocyanate resin (Argonaut, 95 mg, 1.6 mmol/g). After shaking for 4 h the resin was filtered off and the filtrate evaporated to give a gum (29 mg), which was further purified by chromatography on silica gel, eluting with dichloromethane:ethanol:0.880 ammonia 100:0:0-95:5:0.5, followed by mass directed preparative HPLC to give the title compound (7.6 mg).

Workup

  1. stirringthe mixture stirred at 22° C. for 24 h
  2. washeluted with methanol
  3. customEvaporation of the methanolic ammonia fraction

Sources & evidence

ORD record
ord-1054881519454b32a6364b9cd913a0a2
Source dataset
uspto-grants-2006_09
Patent number
US07101882B2

Reaction notes

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