Acetonitrile → HCID 67177495, compound

HRID 1698040Notes

Reaction equation

HRID 1698040 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][C@@H:23]2[CH3:28])[C:5]2[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH:8]([CH2:19][C:20]#[N:21])[C:6]=2[N:7]=1.B(O)O.[C:32]([O-:35])(=O)C.[K+].[C:37](#[N:39])[CH3:38]>O.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:20]([CH2:19][C@@H:8]1[C:6]2[N:7]=[C:2]([C:8]3[CH:19]=[CH:20][C:37]([NH:39][C:32]([NH:3][CH2:4][CH3:5])=[O:35])=[CH:38][CH:6]=3)[N:3]=[C:4]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][C@@H:23]3[CH3:28])[C:5]=2[CH2:11][CH2:10][N:9]1[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])#[N:21]

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 61668Boronic AcidHCID 517044Potassium AcetateHCID 86667309HCID 86667309, compound

Product 1

HCID 67177495HCID 67177495, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×

Conditions

Temperature
90 °C

Procedure

Step 2—Synthesis of compounds xp1 and xp2: Tert-butyl 2-chloro-8-(cyanomethyl)-4-((S)-3-methylmorpholino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate (0.494 g, 0.00121 mol), [4-Ethylureido)phenyl]boronic acid, pinacol ester (0.471 g, 0.00162 mol), Tetrakis(triphenylphosphine)palladium(0) (0.1019 g, 8.818E-5 mol) Sodium carbonate (0.205 g, 0.00193 mol) and Potassium acetate (0.205 g, 0.00209 mol) were combined, nitrogen purged three times, added dry Acetonitrile (10.0 mL, 0.191 mol) followed by deoxygenated Water (6.00 mL, 0.333 mol), heated at 90° C. and stirred overnight. The reaction mixture was cooled to room temperature and stirred for 2 days. The reaction mixture was diluted with water, extracted three times with 10% MeOH in dichloromethane, dried over Magnesium sulfate, filtered, concentrated, chromatographed through silica gel (40 g, 0-100% EtOAc in heptane), purified by HPLC, and the diastereomers were separated out by SFC.

Workup

  1. customnitrogen purged three times
  2. temperatureThe reaction mixture was cooled to room temperature
  3. stirringstirred for 2 days
  4. extractionextracted three times with 10% MeOH in dichloromethane
  5. dry with materialdried over Magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customchromatographed through silica gel (40 g, 0-100% EtOAc in heptane)
  9. custompurified by HPLC
  10. customthe diastereomers were separated out by SFC

Sources & evidence

ORD record
ord-593fecba2095471e828bbdd85cee1b67
Source dataset
uspto-grants-2012_04
Patent number
US08163763B2

Reaction notes

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