Water → 6-[5-(4-Hydroxy-tetrahydro-pyran-4-yl)-pyridin-3-yl]-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid amide

HRID 712660Notes

Reaction equation

HRID 712660 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]3[C:16](=[N:17][CH:18]=2)[N:15]([C:19]([NH2:21])=[O:20])[CH2:14][CH2:13][CH2:12]3)O1.Br[C:24]1[CH:25]=[C:26]([C:30]2([OH:36])[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)[CH:27]=[N:28][CH:29]=1.C([O-])([O-])=O.[Na+].[Na+].O>CCOC(C)=O.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe]>[OH:36][C:30]1([C:26]2[CH:25]=[C:24]([C:9]3[CH:10]=[C:11]4[C:16](=[N:17][CH:18]=3)[N:15]([C:19]([NH2:21])=[O:20])[CH2:14][CH2:13][CH2:12]4)[CH:29]=[N:28][CH:27]=2)[CH2:31][CH2:32][O:33][CH2:34][CH2:35]1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 1176670474-(5-Bromo-3-pyridinyl)tetrahydro-2H-pyran-4-olHCID 1231626313,4-Dihydro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,8-naphthyridine-1(2h)-carboxamide

Product 1

HCID 1176675506-[5-(4-Hydroxy-tetrahydro-pyran-4-yl)-pyridin-3-yl]-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid amide

Reagents, catalysts & solvents 2

HCID 178477754HCID 178477754, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To the crude 6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid amide (0.21 mmol, which is prepared according to the procedure for Step 3 of Example 16) is added 4-(5-bromo-pyridin-3-yl)-tetrahydro-pyran-4-ol (65.9 mg, 0.26 mmol), PdCl2(DPPF) (7.8 mg, 0.01 mmol) and Na2CO3 (45.1 mg, 0.43 mmol). 0.1 mL of H2O is added and the mixture is heated for 2 hrs at 80° C. The mixture is diluted with 50 mL EtOAc, quenched with 20 mL of saturated aqueous NH4Cl, washed with 2×20 mL of H2O and 1×20 mL of brine. The organic phase is dried with MgSO4, filtered and concentrated. The crude material is applied to a silica preparative TLC plate, and eluted (5% MeOH/CH2Cl2) to give 73 mg of 6-[5-(4-Hydroxy-tetrahydro-pyran-4-yl)-pyridin-3-yl]-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid amide.

Workup

  1. customquenched with 20 mL of saturated aqueous NH4Cl
  2. washwashed with 2×20 mL of H2O and 1×20 mL of brine
  3. dry with materialThe organic phase is dried with MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. washeluted (5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-9e15d422f6a745c8a7d9762d1058fe98
Source dataset
uspto-grants-2015_11
Patent number
US09181272B2

Reaction notes

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