Potassium Phosphate, Tribasic → N-(5-cyanopyridin-2-yl)-6-cyclopropyl-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

HRID 1777871Notes

Reaction equation

HRID 1777871 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[N:10][C:11]=1[CH:12]([O:15][CH3:16])[O:13][CH3:14])[N:8]([C:17]([NH:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]#[N:27])=[CH:22][N:21]=1)=[O:18])[CH2:7][CH2:6][CH2:5]2.[CH:28]1(B(O)O)[CH2:30][CH2:29]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C(Cl)Cl.CC([O-])=O.CC([O-])=O.[Pd+2].O.C1(C)C=CC=CC=1>[C:26]([C:23]1[CH:24]=[CH:25][C:20]([NH:19][C:17]([N:8]2[C:9]3[C:4](=[CH:3][C:2]([CH:28]4[CH2:30][CH2:29]4)=[C:11]([CH:12]([O:15][CH3:16])[O:13][CH3:14])[N:10]=3)[CH2:5][CH2:6][CH2:7]2)=[O:18])=[N:21][CH:22]=1)#[N:27]

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 1180363436-bromo-N-(5-cyanopyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide2×

Product 1

HCID 118037011N-(5-cyanopyridin-2-yl)-6-cyclopropyl-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

A tube was charged with 6-bromo-N-(5-cyanopyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide (intermediate 2H, 30 mg, 0.069 mmol), cyclopropylboronic acid (7.75 mg, 0.090 mmol), tricyclohexylphosphine (0.195 mg, 0.694 μmol), K3PO4 (51.6 mg, 0.243 mmol), toluene (0.5 ml) and H2O (0.05 ml) and flushed with argon. Then, Pd(OAc)2 (0.779 mg, 3.47 μmol) was added, the tube was sealed and the reaction mixture was stirred at 100° C. for 1 h. The reaction mixture was cooled to room temperature, diluted with DCM and washed with water. The organic phase was then dried over Na2SO4, filtered and evaporated. The crude material was purified by supercritical fluid chromatography (SFC 1, DEAP column) to give the title compound as a colorless solid. (UPLC-MS 3) tR 1.25 min; ESI-MS 394.2 [M+H]+.

Workup

  1. customflushed with argon
  2. customthe tube was sealed
  3. temperatureThe reaction mixture was cooled to room temperature
  4. washwashed with water
  5. dry with materialThe organic phase was then dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude material was purified by supercritical fluid chromatography (SFC 1, DEAP column)

Sources & evidence

ORD record
ord-9eb38e188680488586a94775712ccc93
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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