Diisopropylamine → HCID 59375617, compound

HRID 2193024Notes

Reaction equation

HRID 2193024 reaction equation
[Br:1][C:2]1[CH:23]=[CH:22][C:5]2[C:6]([CH:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[N:7][C:8]3[C:9](I)=[CH:10][NH:11][C:12](=[O:14])[C:13]=3[C:4]=2[CH:3]=1.O1C=C[CH:26]=[C:25]1P(C1OC=CC=1)C1OC=CC=1.C(NC(C)C)(C)C.C([C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][N:50]=1)#C>CN(C=O)C.C(O)(C(F)(F)F)=O.[CH2-]C=C.[CH2-]C=C.Cl[Pd+].Cl[Pd+].[Cu](I)I.C(#N)C>[Br:1][C:2]1[CH:23]=[CH:22][C:5]2[C:6]([CH:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[N:7][C:8]3[C:9]([C:25]#[C:26][C:52]4[CH:51]=[N:50][CH:49]=[CH:54][CH:53]=4)=[CH:10][NH:11][C:12](=[O:14])[C:13]=3[C:4]=2[CH:3]=1

Participants

10

Reactant 4

HCID 7912DiisopropylamineHCID 137268EthynylpyridineHCID 521585Tris(furan-2-yl)phosphaneHCID 67417233HCID 67417233, compound

Product 1

HCID 59375617HCID 59375617, compound

Reagents, catalysts & solvents 5

HCID 61538Palladium, di-mu-chlorobis(eta3-2-propenyl)di-CatalystHCID 83717Copper iodideCatalystHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
45 °C

Procedure

9-bromo-4-iodo-6-(tetrahydro-2H-pyran-4-yl)benzo[c]-1,6-naphthyridin-1(2H)-one (50 mg, 0.10 mmol), di-mu-chlorobis[(eta-allyl)palladium(II)] (2.3 mg, 6.2 μmol), copper iodide (2.4 mg, 0.012 mmol) and tri(2-furyl)phosphine (2.9 mg, 0.012 mmol) were added to a vial, followed by acetonitrile (1.0 mL), diisopropylamine (44 uL, 0.71 mmol) and 2-ethynyl pyridine (32 mg, 0.31 mmol). The resulting suspension was heated to 45° C. and stirred for four hours. The reaction mixture was diluted with 4 mL DMF and 100 uL TFA, then purified directly by preparative reverse phase HPLC eluting with an acetonitrile/water gradient (with 0.05% TFA as a modifier) to afford 9-bromo-4-(pyridin-3-ylethynyl)-6-(tetrahydro-2H-pyran-4-yl)benzo[c]-1,6-naphthyridin-1(2H)-one. 1H NMR (500 MHz, DMSO-D6) δ 12.38 (br s, 1H), 10.28 (s, 1H), 8.75 (s, 1H), 8.56 (d, 1H), 8.54 (d, 1H), 8.09 (s, 1H), 7.93 (overlapping t, 2H), 7.49 (dd, 1H), 4.02 (overlapping m, 3H), 3.65 (t, 2H), 2.11 (m, 2H), 1.89 (d, 2H). LRMS (ESI) calc'd for (C24H18BrN3O2) [M+H]+, 460.1; found 460.0.

Workup

  1. custompurified directly by preparative reverse phase HPLC
  2. washeluting with an acetonitrile/water gradient (with 0.05% TFA as a modifier)

Sources & evidence

ORD record
ord-1eb5a0bbacab423eb7e8c63883d86e93
Source dataset
uspto-grants-2012_12
Patent number
US08329722B2

Reaction notes

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