Methanol → N-{[(2S)-4-(3,4-dichlorobenzyl)morpholin-2-yl]methyl}-N'-[(2-methyl-2H-tetraazol-5-yl)methyl]urea

HRID 1371450Notes

Reaction equation

HRID 1371450 reaction equation
Cl.[CH3:2][N:3]1[N:7]=[N:6][C:5]([CH2:8][NH2:9])=[N:4]1.Cl.[Cl:11][C:12]1[CH:13]=[C:14]([CH:36]=[CH:37][C:38]=1[Cl:39])[CH2:15][N:16]1[CH2:21][CH2:20][O:19][C@@H:18]([CH2:22][NH:23][C:24](=O)[O:25]C2C=CC([N+]([O-])=O)=CC=2)[CH2:17]1.C(N(CC)C(C)C)(C)C.CO>CN(C)C=O>[Cl:11][C:12]1[CH:13]=[C:14]([CH:36]=[CH:37][C:38]=1[Cl:39])[CH2:15][N:16]1[CH2:21][CH2:20][O:19][C@@H:18]([CH2:22][NH:23][C:24]([NH:9][CH2:8][C:5]2[N:6]=[N:7][N:3]([CH3:2])[N:4]=2)=[O:25])[CH2:17]1

Participants

6

Reactant 4

HCID 887MethanolHCID 81531DiisopropylethylamineHCID 13789253(2-methyl-2H-1,2,3,4-tetrazol-5-yl)methanamine hydrochlorideHCID 867603444-Nitrophenyl [(2S)-4-(3,4-dichlorobenzyl)morpholin-2-yl]methylcarbamate Hydrochloride

Product 1

HCID 21070809N-{[(2S)-4-(3,4-dichlorobenzyl)morpholin-2-yl]methyl}-N'-[(2-methyl-2H-tetraazol-5-yl)methyl]ureaYield 86.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Intermediate 30 (0.041 g) was added to a stirred solution of Intermediate 29 (0.110 g) in N,N-dimethylformamide (2 ml) at 22° C., and N,N-diisopropylethylamine (0.052 ml) was added. After stirring for 20 h, the mixture was applied in two equal portions to ion exchange cartridges (10 g Isolute SCX pre conditioned with methanol). Elution with methanol (3 column volumes) followed by 10% 0.880 ammonia in methanol (2 column volumes) and evaporation of the first basic fractions in vacuo gave the crude product. Purification by Biotage flash chromatography on silica gel (8 g cartridge), eluting with 100:8:1 dichloromethane/ethanol/0.880 ammonia, gave the title compound as a white solid, (0.0828 g).

Workup

  1. washElution with methanol (3 column volumes)
  2. customfollowed by 10% 0.880 ammonia in methanol (2 column volumes) and evaporation of the first basic fractions in vacuo
  3. customgave the crude product
  4. customPurification by Biotage flash chromatography on silica gel (8 g cartridge)
  5. washeluting with 100:8:1 dichloromethane/ethanol/0.880 ammonia

Sources & evidence

ORD record
ord-8dc4361d18b449948acbb4e7a08b34a7
Source dataset
uspto-grants-2007_01
Patent number
US07157457B2

Reaction notes

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