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

HRID 1509407Notes

Reaction equation

HRID 1509407 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][C@H:12]([C:14]([N:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)=[O:15])[CH2:11][C@H:10]([N:22]([C:27](=[O:31])[C:28]([OH:30])=O)[CH2:23][CH:24]([CH3:26])[CH3:25])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[CH3:54][O:55][CH2:56][CH2:57][CH2:58][CH2:59][NH:60][C:61]1[C:62]([NH2:67])=[CH:63][CH:64]=[CH:65][CH:66]=1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[CH3:54][O:55][CH2:56][CH2:57][CH2:58][CH2:59][NH:60][C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][C:62]=1[NH:67][C:28](=[O:30])[C:27]([N:22]([CH2:23][CH:24]([CH3:25])[CH3:26])[C@H:10]1[CH2:11][C@@H:12]([C:14]([N:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)=[O:15])[CH2:13][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[CH2:9]1)=[O:31]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 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 58355733N-(4-methoxybutyl)benzene-1,2-diamine

Product 1

HCID 58355596tert-butyl (3S,5R)-3-{[({2-[(4-methoxybutyl)amino]phenyl}amino)(oxo)acetyl](2-methylpropyl)amino}-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylateYield 63.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

{[(3S,5R)-1-(tert-Butoxycarbonyl)-5-(morpholin-4-ylcarbonyl)piperidin-3-yl](2-methylpropyl)amino}(oxo)acetic acid (10.3 g), HOBt (4.13 g) and WSC.HCl (6.28 g) were dissolved in DMF (50 ml), N-(4-methoxybutyl)benzene-1,2-diamine (4.67 g) and diisopropylethylamine (11.3 ml) were added, and the mixture was stirred at room temperature for 15 hr and at 60° C. for 2 hr. The reaction mixture was concentrated, and the residue was diluted with aqueous sodium bicarbonate, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate was concentrated under reduced pressure to give the object product (9.11 g).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additionthe residue was diluted with aqueous sodium bicarbonate
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. washa fraction eluted with ethyl acetate
  8. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-2f0953e5d60044b3a2ff88e172b3672d
Source dataset
uspto-grants-2015_12
Patent number
US09221836B2

Reaction notes

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