Acetonitrile → HCID 59239143, compound

HRID 1698045Notes

Reaction equation

HRID 1698045 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[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:31]([O-:34])(=O)C.[K+].[C:36](#[N:38])[CH3:37]>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:36]([NH:38][C:31]([NH:3][CH2:4][CH3:5])=[O:34])=[CH:37][CH:6]=3)[N:3]=[C:4]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[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 86667310HCID 86667310, compound

Product 1

HCID 59239143HCID 59239143, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×

Conditions

Temperature
90 °C

Procedure

Step 2—Synthesis of compounds xy1 and xy2: Tert-butyl 2-chloro-8-(cyanomethyl)-4-morpholino-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate (0.803 g, 0.00204 mol), [4-Ethylureido)phenyl]boronic acid, pinacol ester (0.778 g, 0.00268 mol), Tetrakis(triphenylphosphine)palladium(0) (0.148 g, 0.000128 mol) Sodium carbonate (0.334 g, 0.00315 mol) and Potassium acetate (0.330 g, 0.00336 mol) were combined, nitrogen purged three times, added dry Acetonitrile (17.0 mL, 0.325 mol) followed by deoxygenated Water (10.0 mL, 0.555 mol), heated at 90° C. and stirred overnight. 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 enantiomers were separated by SFC. Enantiomer 1 1H NMR (400 MHz, DMSO) δ 8.71 (s, 1H), 8.24 (d, J=8.8, 2H), 7.49 (d, J=8.8, 2H), 6.19 (t, J=5.5, 1H), 5.16 (t, J=5.9, 1H), 4.22 (s, 1H), 3.84-3.73 (m, 2H), 3.73-3.55 (m, 4H), 3.34 (m, 3H), 3.17-2.90 (m, 4H), 2.82 (s, 1H), 1.48 (s, 9H), 1.13 (t, J=7.2, 1H), 1.06 (t, J=7.2, 3H). LC/MS-m/z+522.2 (M+H)+; Enantiomer 2 1H NMR (400 MHz, DMSO) δ 8.71 (s, 1H), 8.24 (d, J=8.8, 2H), 7.49 (d, J=8.8, 2H), 6.19 (t, J=5.6, 1H), 5.16 (t, J=5.9, 1H), 4.18 (s, 1H), 3.78 (dd, J=8.7, 6.2, 2H), 3.72-3.55 (m, 4H), 3.41-3.25 (m, 3H), 3.17-2.90 (m, 4H), 2.84 (d, J=11.0, 1H), 1.47 (d, J=9.3, 9H), 1.14 (t, J=7.2, 1H), 1.09-1.01 (m, 3H). LC/MS-m/z+522.3 (M+H)+

Workup

  1. customnitrogen purged three times
  2. extractionextracted three times with 10% MeOH in dichloromethane
  3. dry with materialdried over Magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customchromatographed through silica gel (40 g, 0-100% EtOAc in heptane)
  7. custompurified by HPLC
  8. customthe enantiomers were separated by SFC

Sources & evidence

ORD record
ord-02b547c969834757b24185aae3668fca
Source dataset
uspto-grants-2012_04
Patent number
US08163763B2

Reaction notes

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