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 1184136Notes

Reaction equation

HRID 1184136 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]

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 58355140tert-butyl (3S,5R)-3-{{({2-methoxy-6-{(4-methoxybutyl)amino}phenyl}amino)(oxo)acetyl}(2-methylpropyl)amino}-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylateYield 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-50f05c8b25e44020836b4584973f7fa4
Source dataset
uspto-grants-2014_03
Patent number
US08664380B2

Reaction notes

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