1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → {(R)-[4-(2-Morpholin-4-yl-ethoxy)-phenyl]-[(1S,2S)-2-phenyl-1-(4-propionyl-thiazol-2-ylcarbamoyl)-propylcarbamoyl]-methyl}-carbamic acid-tert-butyl ester

HRID 32821Notes

Reaction equation

HRID 32821 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)=[CH:15][CH:14]=1)[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].COC1C=CC([C@@H]2C(=O)[N:39]([C@@H:42]([C@H:55]([C:57]3[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=3)[CH3:56])[C:43]([NH:45][C:46]3[S:47][CH:48]=[C:49]([C:51](=[O:54])[CH2:52][CH3:53])[N:50]=3)=[O:44])C(=O)N2)=CC=1.Cl.CN(C)CCCN=C=NCC>O1CCCC1>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]([C:13]1[CH:14]=[CH:15][C:16]([O:19][CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)=[CH:17][CH:18]=1)[C:10](=[O:12])[NH:39][C@H:42]([C:43](=[O:44])[NH:45][C:46]1[S:47][CH:48]=[C:49]([C:51](=[O:54])[CH2:52][CH3:53])[N:50]=1)[C@H:55]([C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1)[CH3:56])([CH3:3])([CH3:2])[CH3:4]

Participants

5

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11577042(2S,3S)-2-[(R)-4-(4-Methoxy-phenyl)-2,5-dioxo-imidazolidin-1-yl]-3-phenyl-N-(4-propionyl-thiazol-2-yl)-butyramideHCID 68620207(R)-tert-butoxycarbonylamino-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-acetic acid

Product 1

HCID 86603386{(R)-[4-(2-Morpholin-4-yl-ethoxy)-phenyl]-[(1S,2S)-2-phenyl-1-(4-propionyl-thiazol-2-ylcarbamoyl)-propylcarbamoyl]-methyl}-carbamic acid-tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(R)-tert-butoxycarbonylamino-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-acetic acid (≈2.93 mmol) was dissolved in tetrahydrofuran (60 mL) and (2S,3S)-2-amino-3-phenyl-N-(4-propionyl-thiazol-2-yl)-butyramide (500 mg, 1.58 mmol) (prepared as described in example 4) was added followed by 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (600 mg, 3.12 mmol) at 0° C. The reaction mixture was allowed to slowly warm to room temperature. After stirring for 5.5 hours the reaction mixture was partitioned between ethyl acetate and brine, the organic extract was dried over sodium sulfate and concentrated in vacuo. The resulting residue purified by chromatography over silica gel eluted first with ethyl acetate and then gradient eluted with dichloromethane containing from 0 to 10% methanol. {(R)-[4-(2-Morpholin-4-yl-ethoxy)-phenyl]-[(1S,2S)-2-phenyl-1-(4-propionyl-thiazol-2-ylcarbamoyl)-propylcarbamoyl]-methyl}-carbamic acid-tert-butyl ester was obtained as a white solid (146 mg, 14%).

Workup

  1. customwas partitioned between ethyl acetate and brine
  2. extractionthe organic extract
  3. dry with materialwas dried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue purified by chromatography over silica gel
  6. washeluted first with ethyl acetate
  7. washgradient eluted with dichloromethane containing from 0 to 10% methanol

Sources & evidence

ORD record
ord-76e6f9b745e8434ba9b0de8020255fc2
Source dataset
uspto-grants-2008_09
Patent number
US07427635B2

Reaction notes

Loading…