Sodium Carbonate → HCID 52934551, compound

HRID 1950795Notes

Reaction equation

HRID 1950795 reaction equation
IC1C2N=C(SC)N=C(NC3C=CC(OC4C=CC=CC=4)=CC=3)C=2C(=O)NC=1.C1(B(O)O)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].CS[C:46]1[N:47]=[C:48]([NH:63][C:64]2[CH:69]=[CH:68][C:67]([O:70][C:71]3[CH:76]=[CH:75][CH:74]=[CH:73][CH:72]=3)=[CH:66][CH:65]=2)[C:49]2[C:55](=[O:56])[NH:54][CH:53]=[C:52]([C:57]3[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=3)[C:50]=2[N:51]=1.[OH:77][CH:78]1[CH2:83][CH2:82][NH:81][CH2:80][CH2:79]1>O1CCOCC1>[OH:77][CH:78]1[CH2:83][CH2:82][N:81]([C:46]2[N:47]=[C:48]([NH:63][C:64]3[CH:65]=[CH:66][C:67]([O:70][C:71]4[CH:76]=[CH:75][CH:74]=[CH:73][CH:72]=4)=[CH:68][CH:69]=3)[C:49]3[C:55](=[O:56])[NH:54][CH:53]=[C:52]([C:57]4[CH:58]=[CH:59][CH:60]=[CH:61][CH:62]=4)[C:50]=3[N:51]=2)[CH2:80][CH2:79]1

Participants

7

Reactant 5

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 79341Piperidin-4-olHCID 58494190HCID 58494190, compoundHCID 58494203HCID 58494203, compound

Product 1

HCID 52934551HCID 52934551, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A 20 mL reaction vessel was charged with 2-(methylthio)-4-(4-phenoxyphenyl amino)pyrido[4,3-d]pyrimidin-5(6H)-one (221a, 182 mg, 0.48 mmol) and N-iodosuccinmide (158 mg, 0.70 mmol) in 8 mL dry DMF. The reaction mixture was stirred at 60° C. for 2 hours. The solvent was removed under reduced pressure yielding the pale brown solid (221b) after being recrystallized from acetonitrile (210 mg, 87%). A 20 mL reaction vessel was charged with 8-iodo-2-(methylthio)-4-(4-phenoxyphenylamino)pyrido[4,3-d]pyrimidin-5(6H)-one (221b, 52 mg, 0.10 mmol), benzenboronic acid (18 mg, 0.15 mmol), tetrakis(triphenyphosphine)palladium (0) (6 mg, 0.005 mmol), and 2.0 M aq. sodium carbonate solution in 6 ml dioxane. The mixture was purged with nitrogen for 30 min. Then the reaction mixture was heated at 80° C. for 3 h. The solvent was removed under reduced pressure yielding the brown residue. The residue was purified by silica gel chromatography using a gradient of 0-5% MeOH in dichloromethane yielding 221c. Then 221 was prepared as described in Example 1g starting from 2-(methylthio)-4-(4-phenoxyphenylamino)-8-phenylpyrido[4,3-d]pyrimidin-5(6H)-one, and 4-hydroxypiperidine to give title compound. MS m/z: 506 (M+H)+.

Workup

  1. customafter being recrystallized from acetonitrile (210 mg, 87%)
  2. customA 20 mL reaction vessel
  3. customThe mixture was purged with nitrogen for 30 min
  4. customThe solvent was removed under reduced pressure
  5. customyielding the brown residue
  6. customThe residue was purified by silica gel chromatography
  7. customThen 221 was prepared

Sources & evidence

ORD record
ord-9175d6187dba43e1b0a7013bc5152366
Source dataset
uspto-grants-2013_03
Patent number
US08404677B2

Reaction notes

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