Pyridine → HCID 69832975, compound

HRID 370041Notes

Reaction equation

HRID 370041 reaction equation
[CH2:1]([O:3][C:4](=[O:31])[N:5]([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C@H:6]1[C:15]2[C:10](=[CH:11][C:12]([O:18][CH3:19])=[C:13]([O:16][CH3:17])[CH:14]=2)[N:9]([C:20](Cl)=[O:21])[C@@H:8]([CH3:23])[CH2:7]1)[CH3:2].[N:32]1[CH:37]=CC=C[CH:33]=1.Cl.CNC.[OH-].[K+]>ClCCl.C(OCC)(=O)C.O>[CH2:1]([O:3][C:4](=[O:31])[N:5]([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C@H:6]1[C:15]2[C:10](=[CH:11][C:12]([O:18][CH3:19])=[C:13]([O:16][CH3:17])[CH:14]=2)[N:9]([C:20](=[O:21])[N:32]([CH3:37])[CH3:33])[C@@H:8]([CH3:23])[CH2:7]1)[CH3:2]

Participants

8

Reactant 4

HCID 1049PyridineHCID 10473Dimethylamine, hydrochlorideHCID 14797Potassium HydroxideHCID 88014990HCID 88014990, compound

Product 1

HCID 69832975HCID 69832975, compoundYield 24%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of cis-4-benzyl-(1-chlorocarbonyl-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl)-carbamic acid ethyl ester (Example 107A) (38 mg, 0.085 mmol), pyridine (0.5 mL), and dimethylamine hydrochloride (12 mg, 0.14 mmol) in anhydrous dichloromethane (1 mL) was stirred at room temperature overnight. Then, 10 mL water and 10 mL 2N KOH were added followed by extration with ethyl acetate (3×10 mL). The combined organic phases were washed with 1N HCl (2×10 mL), 10 mL of a saturated sodium bicarbonate solution, and 10 ml of brine. The combined washed organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. Purification by silica gel chromatography using 0-75% ethyl acetate/hexanes as eluent afforded cis-benzyl-(1-dimethylcarbamoyl-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl)-carbamic acid ethyl ester (Example 108A) (10 mg, 24%) MS m/z 455 (M+), 277 (M+ -178); 1H NMR (CDCl3) δ 3.79 (C6/7, s, 3H), 3.70 (C6/7, s, 3H), 2.79 (N1, s, 6H); and cis-benzyl-[6,7-dimethoxy-2-methyl-1-(5-oxo-penta-1,3-dienylcarbamoyl)-1,2,3,4-tetrahydro-quinolin-4-yl]-carbamic acid ethyl ester (Example 108B) (7 mg, 15%): MS m/z 508 (M+ +1), 329 (M+ -178); 1H NMR (CDCl3) δ 9.46 (aldehyde, d, 1H), 3.85 (C6/7, s, 3H), 3.79 (C6/7, s, 3H).

Workup

  1. washThe combined organic phases were washed with 1N HCl (2×10 mL), 10 mL of a saturated sodium bicarbonate solution, and 10 ml of brine
  2. washThe combined washed organic extracts
  3. dry with materialwere dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-75ea8d9146a0442faf47a7b2f3dcb8a9
Source dataset
uspto-grants-2000_10
Patent number
US06140342

Reaction notes

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