Hydrochloride methanol → 5-((4-chlorophenyl)(hydroxy)methyl)-3-(3-hydroxypropyl)-6-(2-isopropylphenyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 60446Notes

Reaction equation

HRID 60446 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:41])[C:9]2[C:18]3[C:17](=[O:19])[N:16]([CH2:20][CH2:21][CH2:22][O:23]C4CCCCO4)[C:15](=[O:30])[N:14]([CH3:31])[C:13]=3[N:12]=[CH:11][C:10]=2[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2[CH:38]([CH3:40])[CH3:39])=[CH:4][CH:3]=1.Cl.CO>CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:41])[C:9]2[C:18]3[C:17](=[O:19])[N:16]([CH2:20][CH2:21][CH2:22][OH:23])[C:15](=[O:30])[N:14]([CH3:31])[C:13]=3[N:12]=[CH:11][C:10]=2[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2[CH:38]([CH3:39])[CH3:40])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 21893726Hydrochloride methanolHCID 1188755455-((4-chloro phenyl) (hydroxy)methyl)-6-(2-isopropylphenyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

Product 1

HCID 1188755395-((4-chlorophenyl)(hydroxy)methyl)-3-(3-hydroxypropyl)-6-(2-isopropylphenyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dioneYield 35%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 5-((4-chlorophenyl)(hydroxy)methyl)-6-(2-isopropylphenyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (50 mg, 0.087 mmol) in MeOH (2 mL) was added saturated HCl/MeOH (2 mL, MeOH was saturated by HCl gas at 0° C.). The reaction was stirred at RT for 18 h, concentrated then diluted with EA (10 mL) and aq. NaHCO3 (3 mL). The organic layer was dried over Na2SO4 and concentrated to a residue which was purified by Prep HPLC to give 5-((4-chlorophenyl)(hydroxy)methyl)-3-(3-hydroxypropyl)-6-(2-isopropylphenyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (15 mg, 35% yield) as a white solid. 1H NMR (DMSO-d6) δ: 8.61 (s, 1H), 7.48-7.35 (m, 2H), 7.24-7.15 (m, 3H), 7.11-6.96 (m, 3H), 6.74 (m, 0.3H), 6.35 (m, 0.8H), 6.10 (m, 0.3H), 5.66 (m, 0.7H), 3.93 (m, 2H), 3.68 (s, 3H), 3.38 (m, 2H), 2.72 (m, 1H), 1.64 (m, 2H), 1.15 (d, J=6.8 Hz, 2H), 1.08 (m, 3H), 0.81 (d, J=6.7 Hz, 1H). LCMS: [M+ —OH] 476 and TR=2.931 min.

Workup

  1. concentrationconcentrated
  2. additionthen diluted with EA (10 mL) and aq. NaHCO3 (3 mL)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated to a residue which
  5. customwas purified by Prep HPLC

Sources & evidence

ORD record
ord-b411d9aa42f848b5b7db6b16103bc91c
Source dataset
uspto-grants-2016_09
Patent number
US09440972B2

Reaction notes

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