Sodium Carbonate → HCID 59375555, compound

HRID 2192988Notes

Reaction equation

HRID 2192988 reaction equation
Br[C:2]1[CH:28]=[CH:27][C:5]2[C:6]([NH:20][C@H:21]([CH3:26])[C:22]([CH3:25])([CH3:24])[CH3:23])=[N:7][C:8]3[C:9]([C:15]#[C:16][CH:17]4[CH2:19][CH2:18]4)=[CH:10][NH:11][C:12](=[O:14])[C:13]=3[C:4]=2[CH:3]=1.CC1(C)C(C)(C)OB(C2C=NNC=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C>[CH:17]1([C:16]#[C:15][C:9]2[C:8]3[N:7]=[C:6]([NH:20][C@H:21]([CH3:26])[C:22]([CH3:25])([CH3:23])[CH3:24])[C:5]4[CH:27]=[CH:28][CH:2]=[CH:3][C:4]=4[C:13]=3[C:12](=[O:14])[NH:11][CH:10]=2)[CH2:19][CH2:18]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 59375413HCID 59375413, compound

Product 1

HCID 59375555HCID 59375555, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

To a mixture of 9-bromo-4-(cyclopropylethynyl)-6-{[(1R)-1,2,2-trimethylpropyl]amino}benzo[c]-1,6-naphthyridin-1(2H)-one (104 mg, 0.237 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (92 mg, 0.474 mmol) and 1,1′-bis(dipheylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (38.7 mg, 0.047 mmol) was added DMF (2.4 mL) and the mixture was stirred under an argon atmosphere for five minutes. Sodium carbonate (2N) (0.237 mL, 0.474 mmol) was added, and the mixture was further degassed with argon. The reaction was then heated to 130° C. for 35 minutes using microwave irradiation, then quenched with the dropwise addition to a dilute aqueous NaHCO3 solution. The crude product mixture was filtered and purified via silica gel chromatography using 0.5-10% CH3OH in CH2Cl2 as eluent to afford the title compound 4-(cyclopropylethynyl)-6-{[(1R)-1,2,2-trimethylpropyl]amino}benzo[c]-1,6-naphthyridin-1(2H)-one. LRMS (APCI) calc'd (C23H25N3O) [M+H]+, 360.2; found 360.2. 1H NMR (500 MHz, DMSO-d6) δ 11.33 (d, 1H), 9.80 (d, 1H), 8.51 (d, 1H), 7.75 (t, 1H), 7.58 (t, 1H), 7.49 (d, 2H), 4.88 (m, 1H), 1.54 (m, 1H), 1.21 (d, 3H), 0.98 (s, 9H), 0.87 (m, 2H), 0.70 (m, 2H).

Workup

  1. customthe mixture was further degassed with argon
  2. custommicrowave irradiation
  3. customquenched with the dropwise addition to a dilute aqueous NaHCO3 solution
  4. filtrationThe crude product mixture was filtered
  5. custompurified via silica gel chromatography

Sources & evidence

ORD record
ord-c34ed01020314bbdb0073cce9d067c5f
Source dataset
uspto-grants-2012_12
Patent number
US08329722B2

Reaction notes

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