1,2-Dimethoxyethane → HCID 118036390, compound

HRID 1777872Notes

Reaction equation

HRID 1777872 reaction equation
Cl[C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[C:4]([NH:10][C:11]([N:13]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([CH:23]([O:26][CH3:27])[O:24][CH3:25])[N:21]=3)[CH2:16][CH2:15][CH2:14]2)=[O:12])[CH:3]=1.[O:28]1[CH2:33][CH:32]=[C:31](B2OC(C)(C)C(C)(C)O2)[CH2:30][CH2:29]1.C([O-])([O-])=O.[Na+].[Na+].COCCOC>CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:8]([C:7]1[C:2]([C:31]2[CH2:32][CH2:33][O:28][CH2:29][CH:30]=2)=[CH:3][C:4]([NH:10][C:11]([N:13]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([CH:23]([O:26][CH3:27])[O:24][CH3:25])[N:21]=3)[CH2:16][CH2:15][CH2:14]2)=[O:12])=[N:5][CH:6]=1)#[N:9]

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 118036382HCID 118036382, compound2×

Product 1

HCID 118036390HCID 118036390, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

N-(4-chloro-5-cyanopyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide (intermediate 2J, 60 mg, 0.155 mmol), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (65.0 mg, 0.309 mmol), PdCl2(PPh3)2 (10.9 mg, 0.015 mmol), Na2CO3 (2 M in water, 0.232 ml, 0.464 mmol) and DME (2 ml) were charged into a sealed vial under argon. The mixture was stirred at 100° C. for 1 h, cooled to room temperature, diluted in EtOAc and washed with sat. aq. NaHCO3 (2×) and brine. The organic layer was dried over Na2SO4, filtered and concentrated under vacuum. The crude material was purified by normal phase chromatography (4 g silica gel cartridge, heptanes/EtOAc 100:0 to 0:100) the product fractions were concentrated to give the title compound as a white solid. (UPLC-MS 3) tR 1.19 min; ESI-MS 436.2 [M+H]+.

Workup

  1. temperaturecooled to room temperature
  2. washwashed with sat. aq. NaHCO3 (2×) and brine
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customThe crude material was purified by normal phase chromatography (4 g silica gel cartridge, heptanes/EtOAc 100:0 to 0:100) the product fractions
  7. concentrationwere concentrated

Sources & evidence

ORD record
ord-06a1c9f3f45343dfbc7b054e0f4c9a24
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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