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1-Hydroxybenzotriazole → tert-butyl (3S,5R)-3-{{({2-methoxy-6-{(4-methoxybutyl)amino}phenyl}amino)(oxo)acetyl}(2-methylpropyl)amino}-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate

HRID 1509465
Notes
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Reaction equation

HRID 1509465 reaction equation
[CH3:1][O:2][C:3]1[C:8]([NH2:9])=[C:7]([NH:10][CH2:11][CH2:12][CH2:13][CH2:14][O:15][CH3:16])[CH:6]=[CH:5][CH:4]=1.[C:17]([O:21][C:22]([N:24]1[CH2:29][C@H:28]([C:30]([N:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)=[O:31])[CH2:27][C@H:26]([N:38]([C:43](=[O:47])[C:44](O)=[O:45])[CH2:39][CH:40]([CH3:42])[CH3:41])[CH2:25]1)=[O:23])([CH3:20])([CH3:19])[CH3:18].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>ClCCCl.C(N(CC)CC)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]([NH:10][CH2:11][CH2:12][CH2:13][CH2:14][O:15][CH3:16])[C:8]=1[NH:9][C:44](=[O:45])[C:43]([N:38]([CH2:39][CH:40]([CH3:41])[CH3:42])[C@H:26]1[CH2:27][C@@H:28]([C:30]([N:32]2[CH2:33][CH2:34][O:35][CH2:36][CH2:37]2)=[O:31])[CH2:29][N:24]([C:22]([O:21][C:17]([CH3:18])([CH3:19])[CH3:20])=[O:23])[CH2:25]1)=[O:47]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 58355189{[(3S,5R)-1-(tert-butoxycarbonyl)-5-(morpholin-4-ylcarbonyl)piperidin-3-yl](2-methylpropyl)amino}(oxo)acetic acidHCID 583557266-Methoxy-2-(4-methoxybutylamino)aniline

Product 1

HCID 58355140
tert-butyl (3S,5R)-3-{{({2-methoxy-6-{(4-methoxybutyl)amino}phenyl}amino)(oxo)acetyl}(2-methylpropyl)amino}-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate
Yield 53.1%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
60 °C

Procedure

6-Methoxy-2-(4-methoxybutylamino)aniline (210 mg), {{(3S,5R)-1-(tert-butoxycarbonyl)-5-(morpholin-4-ylcarbonyl)piperidin-3-yl}(2-methylpropyl)amino}(oxo)acetic acid (308 mg), HOBt (97 mg) and triethylamine (370 μl) were dissolved in 1,2-dichloroethane (15 ml), WSC.HCl (430 mg) was added, and the mixture was stirred at 60° C. for 2 hr. The reaction mixture was concentrated under reduced pressure, diluted with saturated aqueous sodium hydrogen carbonate, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and the solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (2:8)-ethyl acetate was concentrated under reduced pressure to give the object product (240 mg).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additiondiluted with saturated aqueous sodium hydrogen carbonate
  3. extractionthe mixture was extracted with ethyl acetate
  4. dry with materialThe extract was dried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. washa fraction eluted with ethyl acetate-hexane (2:8)-ethyl acetate
  7. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-770f01becb7543df8984daae739743a1
Source dataset
uspto-grants-2015_12
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09221836B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes