4-Methylmorpholine → N-(trityl-oxy)-2-(R)-[(4-methoxybenzenesulfonyl) (4-picolyl)amino]-2-[(N-(2-(2,3-methylenedioxy-phenyl)-ethoxycarbonyl))-4-piperidinyl]acetamide

HRID 399344Notes

Reaction equation

HRID 399344 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([N:12]([CH2:37][C:38]2[CH:43]=[CH:42][N:41]=[CH:40][CH:39]=2)[C@H:13]([CH:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][CH2:26][CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[C:30]4[O:34][CH2:35][O:36][C:29]=34)=[O:24])[CH2:19][CH2:18]2)[C:14]([OH:16])=O)(=[O:11])=[O:10])=[CH:5][CH:4]=1.[C:44]([O:63][NH2:64])([C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1)([C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1.CN1CCOCC1.ON1C2N=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>C(Cl)Cl.C(OCC)(=O)C>[C:44]([O:63][NH:64][C:14](=[O:16])[C@H:13]([N:12]([S:9]([C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)(=[O:11])=[O:10])[CH2:37][C:38]1[CH:39]=[CH:40][N:41]=[CH:42][CH:43]=1)[CH:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][CH2:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[C:30]3[O:34][CH2:35][O:36][C:29]=23)=[O:24])[CH2:19][CH2:18]1)([C:51]1[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=1)([C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1)[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 3015602O-(triphenylmethyl)hydroxylamineHCID 186658192-(R)-[(4-methoxybenzenesulfonyl)(4-picolyl)amino]-2-[(N-(2-(2,3-methylenedioxyphenyl)-ethoxycarbonyl))-4-piperidinyl]acetic acid

Product 1

HCID 86753206N-(trityl-oxy)-2-(R)-[(4-methoxybenzenesulfonyl) (4-picolyl)amino]-2-[(N-(2-(2,3-methylenedioxy-phenyl)-ethoxycarbonyl))-4-piperidinyl]acetamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the crude 2-(R)-[(4-methoxybenzenesulfonyl)(4-picolyl)amino]-2-[(N-(2-(2,3-methylenedioxyphenyl)-ethoxycarbonyl))-4-piperidinyl]acetic acid (0.66 mmol) in methylene chloride (35 ml) is added O-tritylhydroxylamine (547 mg, 1.98 mmol), N-methylmorpholine (0.44 ml, 3.97 mmol), 1-hydroxy-7-azabenzotriazole (90 mg, 0.66 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (165 mg, 0.86 mmol). The reaction mixture is stired at room temperature for 18 hours, diluted with ethyl acetate and washed with water. The aqueous layer is extracted with ethyl acetate, the combined organic layers are washed with brine, dried over sodium sulfate, and concentrated in vacuo. The crude product is purified by silica gel chromatography (2% to 4% methanol in methylene chloride) to provide N-(trityl-oxy)-2-(R)-[(4-methoxybenzenesulfonyl) (4-picolyl)amino]-2-[(N-(2-(2,3-methylenedioxy-phenyl)-ethoxycarbonyl))-4-piperidinyl]acetamide.

Workup

  1. washwashed with water
  2. extractionThe aqueous layer is extracted with ethyl acetate
  3. washthe combined organic layers are washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude product is purified by silica gel chromatography (2% to 4% methanol in methylene chloride)

Sources & evidence

ORD record
ord-1a202d59dc4148bd88cc2f91873995c2
Source dataset
uspto-grants-1998_10
Patent number
US05817822

Reaction notes

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