Lithium hydroxide, monohydrate → 3-(3-hydroxypropyl)-5-isopentyl-1-methyl-6-(5-methylpyridin-3-yloxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 60481Notes

Reaction equation

HRID 60481 reaction equation
O[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:32]=[N:33][CH:34]=[C:35]([CH3:37])[CH:36]=1)[CH2:3][CH:4]([CH3:6])[CH3:5].O[Li].O>C(O)=O.[Zn]>[OH:21][CH2:20][CH2:19][CH2:18][N:14]1[C:15](=[O:17])[C:16]2[C:7]([CH2:2][CH2:3][CH:4]([CH3:6])[CH3:5])=[C:8]([O:30][C:31]3[CH:32]=[N:33][CH:34]=[C:35]([CH3:37])[CH:36]=3)[CH:9]=[N:10][C:11]=2[N:12]([CH3:29])[C:13]1=[O:28]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 1188755335-(1-hydroxy-3-methylbutyl)-1-methyl-6-(5-methylpyridin-3-yloxy)-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

Product 1

HCID 1188755133-(3-hydroxypropyl)-5-isopentyl-1-methyl-6-(5-methylpyridin-3-yloxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dioneYield 15.2%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 284Formic AcidSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 5-(1-hydroxy-3-methylbutyl)-1-methyl-6-(5-methylpyridin-3-yloxy)-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (100 mg, 0.04 mmol) in HCOOH (2 mL) was added Zn dust (64 mg, 0.375 mmol). The reaction was heated at 100° C. for 1 h, cooled to RT and filtered. The filtrate was concentrated, dried to a residue then dissolved in THF (1 ml) and water (1 mL). Next LiOH.H2O (33.6 mg, 0.8 mmol) was added and the reaction was stirred at RT for 10 min then extracted with EA (3×5 mL). The combined organic layers were dried over Na2SO4 and concentrated to a residue which was purified by Prep HPLC to give 3-(3-hydroxypropyl)-5-isopentyl-1-methyl-6-(5-methylpyridin-3-yloxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (2.5 mg, 7% yield) as clear oil. 1H NMR (CDCl3) δ: 8.29 (s, 1H), 8.22 (s, 1H), 8.16 (s, 1H), 6.99 (s, 1H), 4.26 (t, J=6.1 Hz, 2H), 3.72 (s, 3H), 3.56 (d, J=18.8 Hz, 2H), 3.33-3.23 (m, 2H), 3.20 (s, 1H), 2.33 (s, 3H), 1.99-1.92 (m, 2H), 1.68 (dt, J=11.9, 6.0 Hz, 1H), 1.40 (dt, J=10.7, 6.8 Hz, 2H), 0.91 (d, J=6.6 Hz, 6H). LCMS: MH+ 413 and TR=2.549 min.

Workup

  1. temperaturecooled to RT
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated
  4. customdried to a residue
  5. dissolutionthen dissolved in THF (1 ml)
  6. extractionthen extracted with EA (3×5 mL)
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. concentrationconcentrated to a residue which
  9. customwas purified by Prep HPLC

Sources & evidence

ORD record
ord-ea597f5745a44528b1b8d78dbf32a018
Source dataset
uspto-grants-2016_09
Patent number
US09440972B2

Reaction notes

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