Potassium Phosphate, Tribasic → 3-(3-hydroxypropyl)-5-isopentyl-1-methyl-6-(3-(trifluoromethoxy)benzyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 60514Notes

Reaction equation

HRID 60514 reaction equation
C([O:3][CH2:4][CH2:5][CH2:6][N:7]1[C:12](=[O:13])[C:11]2[C:14]([CH2:19][CH2:20][CH:21]([CH3:23])[CH3:22])=[C:15](Br)[CH:16]=[N:17][C:10]=2[N:9]([CH3:24])[C:8]1=[O:25])=O.CC1(C)C(C)(C)OB([CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[C:37]([O:41][C:42]([F:45])([F:44])[F:43])[CH:36]=2)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[OH:3][CH2:4][CH2:5][CH2:6][N:7]1[C:12](=[O:13])[C:11]2[C:14]([CH2:19][CH2:20][CH:21]([CH3:23])[CH3:22])=[C:15]([CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[C:37]([O:41][C:42]([F:43])([F:44])[F:45])[CH:36]=3)[CH:16]=[N:17][C:10]=2[N:9]([CH3:24])[C:8]1=[O:25]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 1188759113-(6-bromo-5-isopentyl-1-methyl-2,4-dioxo-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate2×HCID 131737094HCID 131737094, compound

Product 1

HCID 1188755303-(3-hydroxypropyl)-5-isopentyl-1-methyl-6-(3-(trifluoromethoxy)benzyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dioneYield 29%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of 3-(6-bromo-5-isopentyl-1-methyl-2,4-dioxo-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate (See Compound 48, step 2, 60 mg, 0.144 mmol) in dioxane (4 mL) was added 4,4,5,5-tetramethyl-2-(3-(trifluoromethoxy)benzyl)-1,3,2-dioxaborolane (90 mg, 0.288 mmol), Pd(dppf)Cl2 (10 mg) and aq. 2M K3PO4 (0.8 mL). The reaction was heated at 85° C. for 2 h, cooled to RT and filtered. The filtrate was concentrated, dried to a residue which was purified by Prep HPLC to give 3-(3-hydroxypropyl)-5-isopentyl-1-methyl-6-(3-(trifluoromethoxy)benzyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (20 mg, 28.7% yield) as a white solid. 1H NMR (DMSO-d6) δ: 8.61 (s, 1H), 7.43 (t, J=7.9 Hz, 1H), 7.19 (dd, J=25.5 and 8.5 Hz, 3H), 4.47 (s, 1H), 4.16 (s, 2H), 4.03-3.89 (m, 2H), 3.57 (s, 3H), 3.45 (dd, J=11.0 and 6.0 Hz, 2H), 3.12 (d, J=6.0 Hz, 2H), 1.81-1.64 (m, 2H), 1.51-1.56 (m, 1H), 1.03 (d, J=9.5 Hz, 2H), 0.81 (d, J=6.6 Hz, 6H). LCMS: MH+ 480 and TR=3.320 min.

Workup

  1. temperaturecooled to RT
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated
  4. customdried to a residue which
  5. customwas purified by Prep HPLC

Sources & evidence

ORD record
ord-3f9941e0f070467fa1cd3d4848c49901
Source dataset
uspto-grants-2016_09
Patent number
US09440972B2

Reaction notes

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