Sodium Carbonate → 7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-5-(isopropylamino)-3-methylpyrido[4,3-d]pyrimidin-4(3H)-one

HRID 1805761Notes

Reaction equation

HRID 1805761 reaction equation
Cl[C:2]1[N:11]=[C:10]([NH:12][CH:13]([CH3:15])[CH3:14])[C:9]2[C:8](=[O:16])[N:7]([CH3:17])[CH:6]=[N:5][C:4]=2[CH:3]=1.CC1(C)C(C)(C)OB([C:26]2[CH:27]=[CH:28][C:29]([C:32]([OH:35])([CH3:34])[CH3:33])=[N:30][CH:31]=2)O1.C([O-])([O-])=O.[Na+].[Na+].O1CCOCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.CO.O>[OH:35][C:32]([C:29]1[N:30]=[CH:31][C:26]([C:2]2[N:11]=[C:10]([NH:12][CH:13]([CH3:15])[CH3:14])[C:9]3[C:8](=[O:16])[N:7]([CH3:17])[CH:6]=[N:5][C:4]=3[CH:3]=2)=[CH:27][CH:28]=1)([CH3:34])[CH3:33]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 580929322-[5-(Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]propan-2-olHCID 580929447-Chloro-5-(isopropylamino)-3-methylpyrido[4,3-d]pyrimidin-4(3H)-one

Product 1

HCID 580929667-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-5-(isopropylamino)-3-methylpyrido[4,3-d]pyrimidin-4(3H)-one

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of crude 7-chloro-5-(isopropylamino)-3-methylpyrido[4,3-d]pyrimidin-4(3H)-one (455 mg, ˜1.80 mmol), crude 2-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)propan-2-ol (570 mg, ˜2.10 mmol), Pd(PPh3)4 (208 mg, 0.18 mmol) and Na2CO3 (1.90 g, 18.0 mol) in a mixed solvent of dioxane (30 mL) and H2O (10 mL) was purged with N2, heated at 90° C. for 16 hours, poured into water (400 mL) and extracted with EtOAc (5×70 mL). The combined organic phases were washed with brine (20 mL), dried over Na2SO4, and evaporated to result in a residue that was subjected to chromatography with gradient mixed solvents from DCM/MeOH/28% aqueous NH4OH (24:10:1) to (15:10:1) to afford the title compound. 1H NMR (DMSO-d6) 1.29 (d, J=6.4 Hz, 6H, 2CH3), 1.47 (s, 6H, 2CH3), 3.44 (s, 3H, NCH3), 4.42 (m, 1H), 5.30 (s, 1H, OH), 7.23 (s, 1H), 7.76 (d, J=8.4 Hz, 1H), 8.44 (d, J=8.4 Hz, 1H), 8.45 (s, 1H), 8.75 (d, J=6.8 Hz, 1H, NH), 9.22 (s, 1H); ESI-MS m/z 354.2 (MH+); Anal. Calcd for C19H23N5O2: C, 64.57; H, 6.56; N, 19.82. Found: C, 64.39; H, 6.47; N, 19.75.

Workup

  1. customwas purged with N2
  2. additionpoured into water (400 mL)
  3. extractionextracted with EtOAc (5×70 mL)
  4. washThe combined organic phases were washed with brine (20 mL)
  5. dry with materialdried over Na2SO4
  6. customevaporated
  7. customto result in a residue that

Sources & evidence

ORD record
ord-0777b7365384453fa184a8f8af1f9505
Source dataset
uspto-grants-2013_01
Patent number
US08354526B2

Reaction notes

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