5-(1-hydroxy-3-methylbutyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy) propyl)-6-(3-(trifluoromethoxy)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione → 5-(1-hydroxy-3-methylbutyl)-3-(3-hydroxypropyl)-1-methyl-6-(3-(trifluoromethoxy)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 60508Notes

Reaction equation

HRID 60508 reaction equation
[OH:1][CH:2]([C:7]1[C:16]2[C:15](=[O:17])[N:14]([CH2:18][CH2:19][CH2:20][O:21]C3CCCCO3)[C:13](=[O:28])[N:12]([CH3:29])[C:11]=2[N:10]=[CH:9][C:8]=1[O:30][C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([O:37][C:38]([F:41])([F:40])[F:39])[CH:32]=1)[CH2:3][CH:4]([CH3:6])[CH3:5]>Cl.CO.CC(=O)OCC.O>[OH:1][CH:2]([C:7]1[C:16]2[C:15](=[O:17])[N:14]([CH2:18][CH2:19][CH2:20][OH:21])[C:13](=[O:28])[N:12]([CH3:29])[C:11]=2[N:10]=[CH:9][C:8]=1[O:30][C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([O:37][C:38]([F:39])([F:41])[F:40])[CH:32]=1)[CH2:3][CH:4]([CH3:5])[CH3:6]

Participants

5

Reactant 1

HCID 1188755245-(1-hydroxy-3-methylbutyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy) propyl)-6-(3-(trifluoromethoxy)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

Product 1

HCID 1188755015-(1-hydroxy-3-methylbutyl)-3-(3-hydroxypropyl)-1-methyl-6-(3-(trifluoromethoxy)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dioneYield 38.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 21893726Hydrochloride methanolSolvent

Procedure

5-(1-hydroxy-3-methylbutyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-6-(3-(trifluoromethoxy)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (60 mg, 0.104 mmol) was dissolved in 2N HCl/MeOH (5 mL). The reaction was stirred at RT for 1 h then diluted with EA (10 mL) and water (10 mL). The organic layer was washed with brine (10 mL), dried over Na2SO4 and concentrated to a residue which was purified by Prep HPLC to give 5-(1-hydroxy-3-methylbutyl)-3-(3-hydroxypropyl)-1-methyl-6-(3-(trifluoromethoxy)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (20 mg, 38.5% yield) as a white solid. 1H NMR (DMSO-d6) δ: 8.59 (s, 1H), 7.48 (t, J=8.4 Hz, 1H), 7.09 (d, J=8.4 Hz, 1H), 6.98-6.92 (m, 3H), 5.62-5.60 (m, 2H), 4.54 (t, J=5.2 Hz, 1H), 4.06-4.01 (m, 2H), 3.60 (s, 3H), 3.46-3.52 (m, 2H), 1.92-1.90 (m, 1H), 1.80-1.72 (m, 3H), 1.24-1.19 (m, 1H), 0.83 (d, J=6.8 Hz, 3H), 0.75 (d, J=6.8 Hz, 3H). LCMS: MH+ 498 and TR=3.186 min.

Workup

  1. washThe organic layer was washed with brine (10 mL)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated to a residue which
  4. customwas purified by Prep HPLC

Sources & evidence

ORD record
ord-c23e12f0fda84821ab2d87945794f82d
Source dataset
uspto-grants-2016_09
Patent number
US09440972B2

Reaction notes

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