Methanol → 8-Cyclopentyl-6-[3-(Hydroxymethyl)phenyl]-4-Methyl-2-(Methylamino)pyrido[2,3-D]pyrimidin-7(8h)-One

HRID 472209Notes

Reaction equation

HRID 472209 reaction equation
Br[C:2]1[C:14](=[O:15])[N:13]([CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)[C:5]2[N:6]=[C:7]([NH:11][CH3:12])[N:8]=[C:9]([CH3:10])[C:4]=2[CH:3]=1.[OH:21][CH2:22][C:23]1[CH:24]=[C:25](B(O)O)[CH:26]=[CH:27][CH:28]=1.CO.C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1.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>[CH:16]1([N:13]2[C:5]3[N:6]=[C:7]([NH:11][CH3:12])[N:8]=[C:9]([CH3:10])[C:4]=3[CH:3]=[C:2]([C:27]3[CH:26]=[CH:25][CH:24]=[C:23]([CH2:22][OH:21])[CH:28]=3)[C:14]2=[O:15])[CH2:20][CH2:19][CH2:18][CH2:17]1

Participants

7

Reactant 4

HCID 887MethanolHCID 516892Sodium BicarbonateHCID 2734662[3-(Hydroxymethyl)phenyl]boronic acidHCID 592588576-Bromo-8-cyclopentyl-4-methyl-2-methylamino-8H-pyrido[2,3-d]pyrimidin-7-one

Product 1

HCID 454801678-Cyclopentyl-6-[3-(Hydroxymethyl)phenyl]-4-Methyl-2-(Methylamino)pyrido[2,3-D]pyrimidin-7(8h)-OneYield 81.24%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Procedure

6-Bromo-8-cyclopentyl-4-methyl-2-methylamino-8H-pyrido[2,3-d]pyrimidin-7-one (5.00 g, 14.83 mmol), 3-(hydroxymethyl)phenylboronic acid (3.38 g, 22.24 mmol) and Pd(PPh3)4 (0.685 g, 0.593 mmol) were suspended in Toluene (20 mL), MeOH (10 mL) and sat. NaHCO3 (10 mL) and then heated to 100° C. overnight. The reaction was deemed complete by MS and TLC. The organic layer was injected directly onto a column, eluting with CH2Cl2 then 4% MeOH in CH2Cl2. The fractions containing the desired material, as deemed by MS, were combined and evaporated in vacuo to give a greenish beige solid. This was triturated with MeCN and filtered to give crop one, 4.7 g. A second crop was obtained of 0.25 g. A third crop was obtained of 0.10 g. The three crops were deemed to be of sufficient purity based on NMR's and were combined and washed again with MeCN to give a solid (4.39 g, 81.24%).

Workup

  1. washeluting with CH2Cl2
  2. additionThe fractions containing the desired material
  3. customevaporated in vacuo
  4. customto give a greenish beige solid
  5. customThis was triturated with MeCN
  6. filtrationfiltered
  7. customto give crop one, 4.7 g
  8. customA second crop was obtained of 0.25 g
  9. customA third crop was obtained of 0.10 g
  10. washwashed again with MeCN

Sources & evidence

ORD record
ord-9486f615064d4c9b83b5387b874f558d
Source dataset
uspto-grants-2014_01
Patent number
US08633204B2

Reaction notes

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