Ethyl Acetate → 6-(2,4-Difluorophenoxy)-8-ethyl-2-(3-hydroxy-tetrahydro-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8h)-one

HRID 270728Notes

Reaction equation

HRID 270728 reaction equation
[F:1][C:2]1[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:3]=1[O:4][C:5]1[C:21](=[O:22])[N:20]([CH2:23][CH3:24])[C:8]2[N:9]=[C:10]([NH:13][CH:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[N:11]=[CH:12][C:7]=2[CH:6]=1.N[C@@H]1CC[O:34]C[C@H]1O.C(OCC)(=O)C>CN1CCCC1=O>[F:1][C:2]1[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:3]=1[O:4][C:5]1[C:21](=[O:22])[N:20]([CH2:23][CH3:24])[C:8]2[N:9]=[C:10]([NH:13][CH:14]3[CH2:19][CH2:18][O:17][CH2:16][CH:15]3[OH:34])[N:11]=[CH:12][C:7]=2[CH:6]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 234345386-(2,4-Difluorophenoxy)-8-ethyl-2-(tetrahydro-2h-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8h)-oneHCID 54857363trans-4-Aminotetrahydropyran-3-ol

Product 1

HCID 234345996-(2,4-Difluorophenoxy)-8-ethyl-2-(3-hydroxy-tetrahydro-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8h)-oneYield 21.9%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A mixture of the sulfone (see example 95 for preparation) (0.50 g, 1.31 mmol) and trans-4-amino-3-hydroxy-tetrahydropyran (0.23 g, 1.97 mmol) (see following ref for preparation: (a) Marquis, Robert W et al J. Med. Chem. (2001), 44(5), 725-736. (b) Gribble, Andrew D et al PCT Int. Appl. (1998), 74 pp. (c) Mochalin, V. B et al Zh. Org. Khim. (1971), 7(4), 825-8). in 2 mL of 1-methyl-2-pyrrolidinone was heated at 100° C. for 12 h. The reaction mixture was cooled, ethyl acetate (15 mL) was added and the organic solution was washed with water (3×, 15 mL), brine and then dried (MgSO4). Evaporation of the solvent under reduced pressure and column chromatography (CH2Cl2/methanol—97/3) afforded 120 mg of product (mpt. 174.9-176.3° C., MS (M+H)=419)

Workup

  1. temperatureThe reaction mixture was cooled
  2. washthe organic solution was washed with water (3×, 15 mL), brine
  3. dry with materialdried (MgSO4)
  4. customEvaporation of the solvent under reduced pressure and column chromatography (CH2Cl2/methanol—97/3)

Sources & evidence

ORD record
ord-9dcf224b676943719f52a102058b5be0
Source dataset
uspto-grants-2008_11
Patent number
US07449581B2

Reaction notes

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