Diisopropylethylamine → (S)-(6-chloro-4-cyclopentyloxy-2-methyl-pyridin-3-ylmethyl)-methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)-amine

HRID 251643Notes

Reaction equation

HRID 251643 reaction equation
Cl.[Cl:2][C:3]1[N:8]=[C:7]([CH3:9])[C:6]([CH2:10]Cl)=[C:5]([O:12][CH:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)[CH:4]=1.[CH3:18][NH:19][C@@H:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:23][CH2:22][CH2:21]1.C(N(CC)C(C)C)(C)C>C(#N)C>[Cl:2][C:3]1[N:8]=[C:7]([CH3:9])[C:6]([CH2:10][N:19]([CH3:18])[C@@H:20]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[CH2:23][CH2:22][CH2:21]2)=[C:5]([O:12][CH:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)[CH:4]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 7128547(1S)-1,2,3,4-Tetrahydro-N-methyl-1-naphthalenamineHCID 865939866-Chloro-3-chloromethyl-4-cyclopentyloxy-2-methyl-pyridine hydrochloride salt

Product 1

HCID 86593987(S)-(6-chloro-4-cyclopentyloxy-2-methyl-pyridin-3-ylmethyl)-methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)-amine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 6-chloro-3-chloromethyl-4-cyclopentyloxy-2-methyl-pyridine hydrochloride salt, (S)-methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)-amine (3.0 g, 18.6 mmol), N,N-diisopropylethylamine (4.0 mL, 22.9 mmol), and anhydrous acetonitrile (50 mL) is stirred for 5 hours at 80° C. The reaction is cooled to ambient temperature and concentrated in vacuo. The obtained residue is dissolved in a mixture of hexane and ethyl:acetate (4:1, 100 mL) and filtered over a small pad of silica gel (35 g), which is subsequently rinsed with additional 100 mL of the same mixture of hexane and ethyl acetate. The filtered solution is concentrated in vacuo and the resultant residue is chromatographed on silica gel (hexane/ethyl Acetate 4:1) to afford (S)-(6-chloro-4-cyclopentyloxy-2-methyl-pyridin-3-ylmethyl)-methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)-amine. 1H NMR: (CDCl3) 7.53 (m, 1H), 7.09 (m, 2H), 7.02 (m, 1H), 6.63 (s, 1H), 4.77 (m, 1H), 3.83 (d, 1H), 3.73 (dd, 1H), 3.56 (d, 1H), 2.73 (m, 2H), 2.63 (s, 3H), 2.07 (m, 2H), 2.04 (s, 3H), 1.98 (m, 2H), 1.82 (m, 4H), 1.68 (m, 4H).

Workup

  1. temperatureThe reaction is cooled to ambient temperature
  2. concentrationconcentrated in vacuo
  3. dissolutionThe obtained residue is dissolved in a mixture of hexane and ethyl:acetate (4:1, 100 mL)
  4. filtrationfiltered over a small pad of silica gel (35 g), which
  5. washis subsequently rinsed with additional 100 mL of the same mixture of hexane and ethyl acetate
  6. concentrationThe filtered solution is concentrated in vacuo
  7. customthe resultant residue is chromatographed on silica gel (hexane/ethyl Acetate 4:1)

Sources & evidence

ORD record
ord-70a58b2e714a418bb22fe801318d29ff
Source dataset
uspto-grants-2011_01
Patent number
US07863454B2

Reaction notes

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