Cyclopropanecarbonyl chloride → N-{[1-(Cyclopropylcarbonyl)piperidin-4-yl]methyl}-N'-{[(2S)-4-(3,4-dichlorobenzyl)morpholin-2-yl]methyl}urea

HRID 1371455Notes

Reaction equation

HRID 1371455 reaction equation
[CH:1]1([C:4](Cl)=[O:5])[CH2:3][CH2:2]1.Cl.Cl.[Cl:9][C:10]1[CH:11]=[C:12]([CH:32]=[CH:33][C:34]=1[Cl:35])[CH2:13][N:14]1[CH2:19][CH2:18][O:17][C@@H:16]([CH2:20][NH:21][C:22]([NH:24][CH2:25][CH:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)=[O:23])[CH2:15]1.C(N(CC)C(C)C)(C)C>ClCCl>[CH:1]1([C:4]([N:29]2[CH2:30][CH2:31][CH:26]([CH2:25][NH:24][C:22]([NH:21][CH2:20][C@@H:16]3[O:17][CH2:18][CH2:19][N:14]([CH2:13][C:12]4[CH:32]=[CH:33][C:34]([Cl:35])=[C:10]([Cl:9])[CH:11]=4)[CH2:15]3)=[O:23])[CH2:27][CH2:28]2)=[O:5])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 77637Cyclopropanecarbonyl chlorideHCID 81531DiisopropylethylamineHCID 69507286HCID 69507286, compound

Product 1

HCID 69507465N-{[1-(Cyclopropylcarbonyl)piperidin-4-yl]methyl}-N'-{[(2S)-4-(3,4-dichlorobenzyl)morpholin-2-yl]methyl}urea

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
23 °C

Procedure

Cyclopropanecarbonyl chloride (0.014 ml) was added to a solution of Intermediate 18 (0.54 g) and N,N-diisopropylethylamine (0.063 ml) in dichloromethane (2 ml). The solution was stirred for 3 h at 23° C. The solvent was removed in vacuo and the residue purified by solid phase extraction (Isolute SCX sulphonic acid column) eluting with methanol followed by 10% 0.880 ammonia solution in methanol. The basic fraction was concentrated in vacuo and the residue was further purified using a silica gel solid phase extraction cartridge (1 g Varian Bond Elut) eluting with 0–1% methanol in ethyl acetate, to give the title compound as a clear gum (0.023 g).

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue purified by solid phase extraction (Isolute SCX sulphonic acid column)
  3. washeluting with methanol
  4. concentrationThe basic fraction was concentrated in vacuo
  5. customthe residue was further purified
  6. extractiona silica gel solid phase extraction cartridge (1 g Varian Bond Elut)
  7. washeluting with 0–1% methanol in ethyl acetate

Sources & evidence

ORD record
ord-a509d44ee9ce4d188a3b0244b8fa2d94
Source dataset
uspto-grants-2007_01
Patent number
US07157457B2

Reaction notes

Loading…