Triethylamine → methyl 3-((R)-1-(2-((R)-3-(2-ethoxyphenoxy)piperidin-1-yl)pyrimidine-5-carboxamido)ethyl)benzoate

HRID 59911

Reaction equation

HRID 59911 reaction equation
[CH2:1]([O:3][C:4]1[CH:25]=[CH:24][CH:23]=[CH:22][C:5]=1[O:6][C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13]2[N:18]=[CH:17][C:16]([C:19]([OH:21])=O)=[CH:15][N:14]=2)[CH2:8]1)[CH3:2].C(N(CC)CC)C.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[NH2:55][C@@H:56]([C:58]1[CH:59]=[C:60]([CH:65]=[CH:66][CH:67]=1)[C:61]([O:63][CH3:64])=[O:62])[CH3:57]>CN(C=O)C.O>[CH2:1]([O:3][C:4]1[CH:25]=[CH:24][CH:23]=[CH:22][C:5]=1[O:6][C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13]2[N:18]=[CH:17][C:16]([C:19]([NH:55][C@@H:56]([C:58]3[CH:59]=[C:60]([CH:65]=[CH:66][CH:67]=3)[C:61]([O:63][CH3:64])=[O:62])[CH3:57])=[O:21])=[CH:15][N:14]=2)[CH2:8]1)[CH3:2]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 55278390(R)-3-(1-Amino-ethyl)-benzoic acid methyl esterHCID 118366221(R)-2-(3-(2-ethoxyphenoxy)piperidin-1-yl)pyrimidine-5-carboxylic acid

Product 1

HCID 118366227methyl 3-((R)-1-(2-((R)-3-(2-ethoxyphenoxy)piperidin-1-yl)pyrimidine-5-carboxamido)ethyl)benzoateYield 76%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
22.5 °C

Procedure

To a stirred solution of (R)-2-(3-(2-ethoxyphenoxy)piperidin-1-yl)pyrimidine-5-carboxylic acid (797 mg, 2.32 mmol) in dry DMF (2.5 mL) at 0° C. were added triethylamine (0.36 mL, 2.5 mmol), 1-hydroxybenzotriazole (470 mg, 3.48 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1666 mg, 3.48 mmol). The mixture was stirred for 5 min and methyl (R)-3-(1-aminoethyl)benzoate (500 mg, 2.32 mmol) was added. The reaction mixture was allowed to warm to 20-25° C. and was stirred for 16 hours. The mixture was poured into water (20 mL) and extracted with ethyl acetate (3 times with 25 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The crude residue was purified via column chromatography to afford methyl 3-((R)-1-(2-((R)-3-(2-ethoxyphenoxy)piperidin-1-yl)pyrimidine-5-carboxamido)ethyl)benzoate (890 mg, 76%). MS (ES+) 505.2 (M+H).

Workup

  1. stirringwas stirred for 16 hours
  2. extractionextracted with ethyl acetate (3 times with 25 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue was purified via column chromatography

Sources & evidence

ORD record
ord-e3f21c9a1d3d410793464f84afd1452b
Source dataset
uspto-grants-2016_09
Patent number
US09440949B2

Linked notes

Loading…