1-Hydroxybenzotriazole → tert-butyl(2R)-2-({cyclopropyl[4-methoxy-3-(3-methoxypropoxy)benzyl]amino}carbonyl)morpholin-4-carboxylate

HRID 872010Notes

Reaction equation

HRID 872010 reaction equation
ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[C:23]([O:27][C:28]([N:30]1[CH2:35][CH2:34][O:33][C@@H:32]([C:36]([OH:38])=O)[CH2:31]1)=[O:29])([CH3:26])([CH3:25])[CH3:24].Cl.[CH3:40][O:41][C:42]1[CH:52]=[CH:51][C:45]([CH2:46][NH:47][CH:48]2[CH2:50][CH2:49]2)=[CH:44][C:43]=1[O:53][CH2:54][CH2:55][CH2:56][O:57][CH3:58]>CN(C)C=O.O.C(N(CC)CC)C>[CH:48]1([N:47]([CH2:46][C:45]2[CH:51]=[CH:52][C:42]([O:41][CH3:40])=[C:43]([O:53][CH2:54][CH2:55][CH2:56][O:57][CH3:58])[CH:44]=2)[C:36]([C@@H:32]2[O:33][CH2:34][CH2:35][N:30]([C:28]([O:27][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:29])[CH2:31]2)=[O:38])[CH2:49][CH2:50]1

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 6559076(2R)-4-((tert-butoxy)carbonyl)morpholine-2-carboxylic acidHCID 67542002n-[4-Methoxy-3-(3-methoxypropoxy)benzyl]cyclopropanamine hydrochloride

Product 1

HCID 59494725tert-butyl(2R)-2-({cyclopropyl[4-methoxy-3-(3-methoxypropoxy)benzyl]amino}carbonyl)morpholin-4-carboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

1-Hydroxybenzotriazole (175 mg), triethylamine (145 μl) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (249 mg) were added to a solution of (2R)-(tert-butoxycarbonyl)morpholin-2-carboxylic acid (200 mg) and N-[4-methoxy-3-(3-methoxypropoxy)benzyl]cyclopropanamine hydrochloride (a compound of Reference Example 1(2), 313 mg) in N,N-dimethylformamide (5 ml) successively and the mixture was stirred at room temperature for 3 hours. Water was added to the mixture under ice-cooling and it was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium bicarbonate and saturated brine successively, dried over sodium sulfate and concentrated in vacuo. The resulted residue was purified with a silica gel column chromatography (eluting solvent: n-hexane/ethyl acetate=1/1) to give tert-butyl(2R)-2-({cyclopropyl[4-methoxy-3-(3-methoxypropoxy)benzyl]amino}carbonyl)morpholin-4-carboxylate (368 mg) as a colorless oil.

Workup

  1. temperaturecooling
  2. extractionit was extracted with ethyl acetate
  3. washThe organic layer was washed with a saturated aqueous solution of sodium bicarbonate and saturated brine successively
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe resulted residue was purified with a silica gel column chromatography (eluting solvent: n-hexane/ethyl acetate=1/1)

Sources & evidence

ORD record
ord-dce39f7e9490414d88c6b3af70cbc803
Source dataset
uspto-grants-2015_03
Patent number
US08975252B2

Reaction notes

Loading…