Potassium Carbonate → N-{[4-(4-{3-[cyclobutyl(methyl)amino]propoxy}phenyl)tetrahydro-2H-pyran-4-yl]methyl}pyridin-2-amine

HRID 273043

Reaction equation

HRID 273043 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][CH2:8][C:9]1([C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=2)[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1.Cl[CH2:23][CH2:24][CH2:25][N:26]([CH3:31])[CH:27]1[CH2:30][CH2:29][CH2:28]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH:27]1([N:26]([CH3:31])[CH2:25][CH2:24][CH2:23][O:21][C:18]2[CH:19]=[CH:20][C:15]([C:9]3([CH2:8][NH:7][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=4)[CH2:10][CH2:11][O:12][CH2:13][CH2:14]3)=[CH:16][CH:17]=2)[CH2:30][CH2:29][CH2:28]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 68576572HCID 68576572, compoundHCID 685779444-{4-[(pyridin-2-ylamino)methyl]tetrahydro-2H-pyran-4-yl}phenol

Product 1

HCID 59837409N-{[4-(4-{3-[cyclobutyl(methyl)amino]propoxy}phenyl)tetrahydro-2H-pyran-4-yl]methyl}pyridin-2-amineYield 30%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-{4-[(pyridin-2-ylamino)methyl]tetrahydro-2H-pyran-4-yl}phenol (386 mg, 1.36 mmol), N-(3-chloropropyl)-N-methylcyclobutanamine (241 mg, 1.496 mmol) and potassium carbonate (280 mg, 2.03 mmol) were stirred in DMF (2 ml) at 45° C. for 24 hours until complete. Reaction was partitioned between ethyl acetate (40 ml) and saturated sodium bicarbonate solution (50 ml), then the organic layer washed with water (50 ml). Organic layer separated and dried over sodium sulphate, filtered and concentrated in vacuo. Crude product purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (100:0:0 to 90:10:1 by volume) to give the title compound (165 mg, 30%). 1H NMR (400 MHz, CDCl3) δ 1.55-1.72 (m, 2H), 1.80-1.99 (m, 6H), 2.00-2.09 (m, 2H), 2.10-2.20 (m, 4H), 2.40 (t, 2H), 2.80 (quintet, 1H), 3.50 (d, 2H), 3.54-3.62 (m, 2H), 3.78-3.88 (m, 2H), 4.00 (m, 3H), 6.20 (d, 1H), 6.50 (t, 1H), 6.92 (d, 2H), 7.22 (d, 2H), 7.32 (t, 1H), 8.00 (d, 1H). LRMS APCI+ m/z 410 [MH]+. HRMS ESI+ m/z 410.2794[MH]+.

Workup

  1. customReaction
  2. customwas partitioned between ethyl acetate (40 ml) and saturated sodium bicarbonate solution (50 ml)
  3. washthe organic layer washed with water (50 ml)
  4. customOrganic layer separated
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customCrude product purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (100:0:0 to 90:10:1 by volume)

Sources & evidence

ORD record
ord-b094daadfc5f46818ac11ce2148bee58
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Linked notes

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