1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → N-{[4-(3,4-Dichlorobenzyl)morpholin-2-yl]methyl}-2-[2-(4-fluorophenyl)-5-methyl-1,3-oxazol-4-yl]acetamide

HRID 2212012Notes

Reaction equation

HRID 2212012 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([CH3:17])=[C:11]([CH2:13][C:14]([OH:16])=O)[N:12]=2)=[CH:4][CH:3]=1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[Cl:41][C:42]1[CH:43]=[C:44]([CH:54]=[CH:55][C:56]=1[Cl:57])[CH2:45][N:46]1[CH2:51][CH2:50][O:49][CH:48]([CH2:52][NH2:53])[CH2:47]1>CN(C)C=O.C(N(CC)C(C)C)(C)C.ClCCl.CO>[NH3:12].[CH3:8][OH:9].[Cl:41][C:42]1[CH:43]=[C:44]([CH:54]=[CH:55][C:56]=1[Cl:57])[CH2:45][N:46]1[CH2:51][CH2:50][O:49][CH:48]([CH2:52][NH:53][C:14](=[O:16])[CH2:13][C:11]2[N:12]=[C:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[O:9][C:10]=2[CH3:17])[CH2:47]1

Participants

10

Reactant 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 10308229[4-(3,4-Dichlorobenzyl)morpholin-2-yl]methylamineHCID 219629032-(2-(4-Fluorophenyl)-5-methyl-1,3-oxazol-4-yl)acetic acid

Product 2

HCID 21705897Ammonia methanolHCID 21962949N-{[4-(3,4-Dichlorobenzyl)morpholin-2-yl]methyl}-2-[2-(4-fluorophenyl)-5-methyl-1,3-oxazol-4-yl]acetamideYield 91.7%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolventHCID 81531DiisopropylethylamineSolvent

Conditions

Temperature
22 °C

Procedure

Intermediate 12 (0.050 g) was treated with N,N-dimethylformamide (0.5 ml) followed by 1-hydroxybenzotriazole hydrate (0.027 g), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.044 g) and Intermediate 1 (0.042 g) in N,N-dimethylformamide (0.5 ml) and N,N-diisopropylethylamine (0.027 ml). The mixture was stirred at 22° C. for 20 h, then left to stand for 6 days. The solution was diluted with dichloromethane (10 ml) and washed successively with dilute aqueous sodium hydrogen carbonate (10 ml) and dilute aqueous sodium chloride (2×10 ml). The organic phase was isolated using a hydrophobic frit (6 ml) and drained directly onto an SCX column (2 g Isolute SPE) which had been prepared by application of methanol. Elution with methanol, then 0.880 ammonia:methanol 10:90 gave the title compound (0.048 g) as an orange glassy solid.

Workup

  1. waitleft
  2. waitto stand for 6 days
  3. washwashed successively with dilute aqueous sodium hydrogen carbonate (10 ml) and dilute aqueous sodium chloride (2×10 ml)
  4. customThe organic phase was isolated
  5. washElution with methanol

Sources & evidence

ORD record
ord-e2affc2001684342beb036dcf7bfdb62
Source dataset
uspto-grants-2006_09
Patent number
US07101882B2

Reaction notes

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