Triethylamine → 2-[6-(4-Chloro-benzyl)-2-(2'-methyl-3,4,5,6-tetrahydro-2H-[1,4']bipyridinyl-4-ylamino)-pyrimidin-4-yl]-propan-2-ol

HRID 451422Notes

Reaction equation

HRID 451422 reaction equation
[Cl:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][C:7]2[N:12]=[C:11]([NH:13][CH:14]3[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]3)[N:10]=[C:9]([C:20]([OH:23])([CH3:22])[CH3:21])[CH:8]=2)=[CH:4][CH:3]=1.Cl[C:27]1[CH:32]=[CH:31][N:30]=[C:29]([CH3:33])[CH:28]=1.C(N(CC)CC)C>S1(CCCC1)(=O)=O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][C:7]2[N:12]=[C:11]([NH:13][CH:14]3[CH2:19][CH2:18][N:17]([C:27]4[CH:32]=[CH:31][N:30]=[C:29]([CH3:33])[CH:28]=4)[CH2:16][CH2:15]3)[N:10]=[C:9]([C:20]([OH:23])([CH3:22])[CH3:21])[CH:8]=2)=[CH:24][CH:25]=1

Participants

6

Reactant 3

HCID 8471Triethylamine2×HCID 5813924-Chloro-2-methylpyridine2×HCID 673418332-[6-(4-Chloro-benzyl)-2-(piperidin-4-ylamino)-pyrimidin-4-yl]-propan-2-ol

Product 1

HCID 533534252-[6-(4-Chloro-benzyl)-2-(2'-methyl-3,4,5,6-tetrahydro-2H-[1,4']bipyridinyl-4-ylamino)-pyrimidin-4-yl]-propan-2-olYield 40%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31347SulfolaneSolvent

Conditions

Temperature
150 °C

Procedure

A solution of 2-[6-(4-chloro-benzyl)-2-(piperidin-4-ylamino)-pyrimidin-4-yl]-propan-2-ol (76 mg, 0.19 mmol), 4-chloro-2-picoline (24 mg, 0.19 mmol) and triethylamine (53 μL, 0.38 mmol) in sulfolane (0.76 mL) was stirred in a preheated oil bath at 150° C. for 30 minutes. After further addition of 4-chloro-2-picoline (24 mg, 0.19 mmol) and triethylamine (53 μL, 0.38 mmol) the solution was stirred for further 60 minutes at 150° C. It was diluted with ethyl acetate (15 mL) and was washed with 1 M aqueous sodium carbonate solution (20 mL), water (15 mL) and brine (15 mL). The combined aqueous layers were extracted with ethyl acetate (15 mL). The organic layer was dried over sodium sulfate. Concentration and purification by chromatography (SiO2, dichloromethane/methanol/triethylamine=95:4.5:0.5) afforded the title compound (34 mg, 40%) as an off-white foam.

Workup

  1. washwas washed with 1 M aqueous sodium carbonate solution (20 mL), water (15 mL) and brine (15 mL)
  2. extractionThe combined aqueous layers were extracted with ethyl acetate (15 mL)
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. concentrationConcentration and purification by chromatography (SiO2, dichloromethane/methanol/triethylamine=95:4.5:0.5)

Sources & evidence

ORD record
ord-3b1d01032bbb4952b20e15c18aba111d
Source dataset
uspto-grants-2013_07
Patent number
US08486967B2

Reaction notes

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