Pyridine → (1R,2S)-1-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-2,3-dihydro-1H-inden-2-yl acetate

HRID 1612124Notes

Reaction equation

HRID 1612124 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]([CH2:28][CH3:29])[C:12]([NH:17][C@@H:18]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH2:20][C@@H:19]2[OH:27])=[N:13][C:14]=1[CH2:15][CH3:16].N1C=CC=CC=1.[C:36](Cl)(=[O:38])[CH3:37]>ClCCl>[C:36]([O:27][C@H:19]1[CH2:20][C:21]2[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=2)[C@H:18]1[NH:17][C:12]1[C:11]([CH2:28][CH3:29])=[N:10][C:9]([C:3]2[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=2[Cl:1])=[C:14]([CH2:15][CH3:16])[N:13]=1)(=[O:38])[CH3:37]

Participants

5

Reactant 3

HCID 1049PyridineHCID 6367Acetyl chlorideHCID 58583246(1R,2S)-1-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-2,3-dihydro-1H-inden-2-ol

Product 1

HCID 10288660(1R,2S)-1-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-2,3-dihydro-1H-inden-2-yl acetate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of (1R,2S)-1-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-2,3-dihydro-1H-inden-2-ol (214 mg, 0.5 mmol) and pyridine (44 μL, 0.55 mmol) in dichloromethane (5 mL) was purged with nitrogen and cooled to 0° C. The light yellow homogenous solution was treated with acetyl chloride (34 μL, 0.48 mmol) with no visible change. The reaction mixture was gradually warmed to RT. After 16 hrs, the volatiles were removed under reduced pressure and the resulting residue was absorbed on 4 g silica gel and purified by Biotage MPLC (40 g column, 15% ethyl acetate/heptane) to afford the title compound as an off-white solid. IR (diffuse reflectance) 2971, 2934, 1743, 1568, 1550, 1498, 1467, 1393, 1372, 1238, 1207, 1177, 1101, 1036, 751 cm−1; OAMS supporting ions at: ESI+ 470.1; MS (EI) m/z 469 (M+); HRMS (FAB) calcd for C25H25CL2N3O2+H1 470.1402, found 470.1404. [α]25D=73 (c 0.60, methylene chloride); Anal. Calcd for C25H25Cl2N3O2: C, 63.83; H, 5.36; N, 8.93. Found: C, 63.45; H, 5.40; N, 8.79.

Workup

  1. temperatureThe reaction mixture was gradually warmed to RT
  2. customthe volatiles were removed under reduced pressure
  3. customthe resulting residue was absorbed on 4 g silica gel
  4. custompurified by Biotage MPLC (40 g column, 15% ethyl acetate/heptane)

Sources & evidence

ORD record
ord-4433d1fc2c424f54b3de2f71a38b1039
Source dataset
uspto-grants-2006_01
Patent number
US06992087B2

Reaction notes

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