Lithium hydroxide, monohydrate → HCID 118875472, compound

HRID 60479Notes

Reaction equation

HRID 60479 reaction equation
O[CH:2]([C:38]1[CH:39]=[N:40][C:41]([C:44]([F:47])([F:46])[F:45])=[CH:42][CH:43]=1)[C:3]1[C:12]2[C:11](=[O:13])[N:10]([CH2:14][CH2:15][CH2:16][O:17]C3CCCCO3)[C:9](=[O:24])[N:8]([CH3:25])[C:7]=2[N:6]=[CH:5][C:4]=1[O:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([O:33][C:34]([F:37])([F:36])[F:35])[CH:28]=1.O[Li].O>C(O)=O.[Zn]>[OH:17][CH2:16][CH2:15][CH2:14][N:10]1[C:11](=[O:13])[C:12]2[C:3]([CH2:2][C:38]3[CH:39]=[N:40][C:41]([C:44]([F:47])([F:46])[F:45])=[CH:42][CH:43]=3)=[C:4]([O:26][C:27]3[CH:32]=[CH:31][CH:30]=[C:29]([O:33][C:34]([F:35])([F:36])[F:37])[CH:28]=3)[CH:5]=[N:6][C:7]=2[N:8]([CH3:25])[C:9]1=[O:24]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 1188755065-(hydroxy(6-(trifluoromethyl)-pyridin-3-yl)methyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-6-(3-(trifluoromethoxy)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

Product 1

HCID 118875472HCID 118875472, compoundYield 29.4%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 284Formic AcidSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 5-(hydroxy(6-(trifluoromethyl)pyridin-3-yl)methyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-6-(3-(trifluoromethoxy)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (40 mg, 0.06 mmol) in HCOOH (2 mL) was added Zn dust (19.5 mg, 0.3 mmol). The reaction was heated at 100° C. for 1 h then cooled to RT and filtered. The filtrate was concentrated and dried to a residue which was dissolved in water (1 ml) and THF (1 mL). Next LiOH.H2O (25 mg, 0.6 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)-1-methyl-6-(3-(trifluoromethoxy)phenoxy)-5-((6-(trifluoromethyl)pyridin-3-yl)methyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (10 mg, 29.4% yield) as clear oil. 1H NMR (CDCl3) δ: 8.65 (s, 1H), 8.40 (s, 1H), 7.78 (d, J=6.8 Hz, 1H), 7.53 (d, J=8.1 Hz, 1H), 7.36 (t, J=8.3 Hz, 1H), 7.01 (d, J=8.3 Hz, 1H), 6.81 (dd, J=8.3, 2.2 Hz, 1H), 6.75 (s, 1H), 4.82 (s, 2H), 4.23 (t, J=6.2 Hz, 2H), 3.57 (t, J=5.5 Hz, 2H), 2.93 (s, 1H), 2.00-1.87 (m, 2H). LCMS: MH+ 571 and TR=3.069 min.

Workup

  1. temperaturethen cooled to RT
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated
  4. customdried to a residue which
  5. dissolutionwas dissolved in water (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-c2a46960945c45ffbb4c4c205cf993e0
Source dataset
uspto-grants-2016_09
Patent number
US09440972B2

Reaction notes

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