4-Methylmorpholine → HCID 67464995, compound

HRID 2043759Notes

Reaction equation

HRID 2043759 reaction equation
Cl.[NH2:2][C@@H:3]([CH2:18][OH:19])[C:4]([N:6]([CH3:17])[C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH2:10][CH2:9][CH2:8]1)=[O:5].CN1CCOCC1.[CH3:27][C:28]1[N:32]([CH2:33][C:34]([N:36]2[CH2:41][CH2:40][CH:39]([C:42](O)=[O:43])[CH2:38][CH2:37]2)=[O:35])[N:31]=[C:30]([C:45]([F:48])([F:47])[F:46])[CH:29]=1.ON1C2C=CC=CC=2N=N1.CC(N=C=NC(C)C)C>O1CCCC1>[OH:19][CH2:18][C@H:3]([NH:2][C:42]([CH:39]1[CH2:40][CH2:41][N:36]([C:34](=[O:35])[CH2:33][N:32]2[C:28]([CH3:27])=[CH:29][C:30]([C:45]([F:46])([F:48])[F:47])=[N:31]2)[CH2:37][CH2:38]1)=[O:43])[C:4]([N:6]([CH3:17])[C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH2:10][CH2:9][CH2:8]1)=[O:5]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 12734DiisopropylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 67460128HCID 67460128, compound2×HCID 67463716HCID 67463716, compound2×

Product 1

HCID 67464995HCID 67464995, compoundYield 54.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (2S)-2-amino-3-hydroxy-N-methyl-N-[(1R)-1,2,3,4-tetrahydro-1-naphthalenyl]propanamide monohydrochloride (546.33 mg, 2.2 mmol) (i.e. the product of Example 17, Step B) and N-methylmorpholine (222.53 mg, 2.2 mmol) in 8 mL of tetrahydrofuran was cooled to 0° C. and 1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinylcarboxylic acid (638.56 mg, 2 mmol) (i.e. the product of Example 17, Step D) was added followed by N-hydroxybenzotriazole (27 mg, 0.2 mmol) and N,N-diisopropylcarbodiimide (265 mg, 2.1 mmol). The reaction mixture was stirred for 16 h at room temperature and filtered. The precipitate was washed with tetrahydrofuran and the resulting filtrate and washings were concentrated in vacuo. The residue was dissolved in dichloromethane and the resulting solution was washed with water, 1 M aqueous hydrochloric acid, water, saturated aqueous solution of sodium bicarbonate and brine, dried over MgSO4 and concentrated in vacuo. The resulting product was purified by medium-pressure liquid chromatography on silica gel using 0-20% methanol in ethyl acetate as eluant to give 600 mg of the title compound as a white solid.

Workup

  1. filtrationfiltered
  2. washThe precipitate was washed with tetrahydrofuran
  3. concentrationthe resulting filtrate and washings were concentrated in vacuo
  4. dissolutionThe residue was dissolved in dichloromethane
  5. washthe resulting solution was washed with water, 1 M aqueous hydrochloric acid, water, saturated aqueous solution of sodium bicarbonate and brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe resulting product was purified by medium-pressure liquid chromatography on silica gel using 0-20% methanol in ethyl acetate as eluant

Sources & evidence

ORD record
ord-baa52d0e05264824a38778dec687d7f8
Source dataset
uspto-grants-2013_11
Patent number
US08586611B2

Reaction notes

Loading…