2-Chloropyrimidine → HCID 11654126, compound

HRID 272959Notes

Reaction equation

HRID 272959 reaction equation
[N:1]1([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3([CH2:22][NH2:23])[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl[C:25]1[N:30]=[CH:29][CH:28]=[CH:27][N:26]=1.C(N(CC)C(C)C)(C)C>CN1CCCC1=O>[N:1]1([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3([CH2:22][NH:23][C:25]4[N:30]=[CH:29][CH:28]=[CH:27][N:26]=4)[CH2:17][CH2:18][O:19][CH2:20][CH2:21]3)=[CH:12][CH:11]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 744042-ChloropyrimidineHCID 81531DiisopropylethylamineHCID 11645410(4-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]tetrahydropyran-4-yl}methylamine

Product 1

HCID 11654126HCID 11654126, compoundYield 17.7%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
180 °C

Procedure

A mixture of {4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydropyran-4-yl}methylamine (100 mg, 0.314 mmol), 2-chloropyrimidine (50 mg, 0.346 mmol) and N,N-diisopropylethylamine (112 μl, 0.629 mmol) in N-methylpyrrolidinone (0.5 ml) was heated at 180° C. in the microwave (Smith Personal Synthesiser) for 600 seconds. The reaction mixture was partitioned between ethyl acetate (10 ml) and saturated NaHCO3 (10 ml). The organic washings were dried over Na2SO4 and concentrated in vacuo to give an oil. The compound was purified by column chromatography on silica gel, eluting with dichloromethane:methanol:ammonia, 100:0:0 to 88:12:1.2. Compound still impure so purified further on the Fraction Lynx automated LC system to give the title compound as a solid (22 mg, 17%) 1H NMR (400 MHz, CDCl3) δ 8.30 (brs, 2H), 7.34 (d, 2H), 6.92 (d, 2H), 6.70 (t, 1H), 4.10 (t, 2H), 3.78-3.84 (m, 2H), 3.62-3.72 (multiple peaks, 4H), 3.44-3.55 (m, 2H), 3.40 (m, 2H), 3.04-3.18 (m, 2H), 1.85-2.25 (multiple peaks, 10H).

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate (10 ml) and saturated NaHCO3 (10 ml)
  2. dry with materialThe organic washings were dried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customto give an oil
  5. customThe compound was purified by column chromatography on silica gel
  6. washeluting with dichloromethane
  7. customCompound still impure so purified further on the Fraction Lynx automated LC system

Sources & evidence

ORD record
ord-5339b251f7644fdb890c499a4d1b16c8
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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