Sodium Iodide → HCID 68499706, compound

HRID 885698Notes

Reaction equation

HRID 885698 reaction equation
[CH3:1][O:2][C:3]1N=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[C:6]2[N:13]1[CH:21]=[C:20]2[C:15](C[CH2:17][CH:18]([NH2:22])[CH2:19]2)=[N:14]1.Br[CH2:24][CH2:25][O:26][C:27]1[CH:32]=[C:31]([F:33])[CH:30]=[C:29]([F:34])[CH:28]=1.[C:35]([O-])([O-])=O.[Cs+].[Cs+].[Na+].[I-]>CN(C=O)C>[F:34][C:29]1[CH:28]=[C:27]([CH:32]=[C:31]([F:33])[CH:30]=1)[O:26][CH2:25][CH2:24][NH:22][CH:18]([CH3:17])[CH2:19][C:20]1[CH:15]=[N:14][N:13]([C:6]2[C:5]3[C:10](=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[CH:35]=3)[N:9]=[CH:8][CH:7]=2)[CH:21]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 22247028HCID 22247028, compoundHCID 595606482-(6-Methoxy-[1,5]naphthyridin-4-yl)4,5,6,7-tetrahydro-2H-indazol-5-ylamine

Product 1

HCID 68499706HCID 68499706, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-ylamine (160 mg, 0.54 mmol) in DMF (3 mL) was added 1-(2-bromo-ethoxy)-3,5-difluoro-benzene (154 mg, 0.65 mmol), Cs2CO3 (267 mg, 0.82 mmol) and catalytic NaI (25 mg, 0.002 mmol). After 48 h at 50° C., the mixture was concentrated, and the residue was dissolved in EtOAc, washed with H2O, dried (MgSO4), and concentrated. The resulting residue was purified by basic reverse phase HPLC to provide 53.8 mg (29%) of the title compound as a brown gum. MS (ESI): exact mass calculated for C25H24F2N4O2, 450.48; m/z found, 451.2 [M+H]+. 1H NMR (500 MHz, CD3OD): 8.74 (d, J=4.9, 1H), 8.01 (d, J=9.2, 1H), 7.95 (s, 1H), 7.71 (d, J=2.7 1H), 7.50-7.48 (m, 2H), 6.61 (dd, J=9.2, 2.1, 2H), 6.52 (tt, J=9.2, 2.2, 1H), 4.14 (t, J=5.3, 2H), 3.90 (s, 3H), 3.13-3.09 (m, 4H), 3.00-2.96 (m, 1H), 2.83 (ddd, J=16.6, 10.7, 5.8, 1H), 2.54-2.51 (m, 1H), 2.26-2.23 (m, 1H), 1.85-1.77 (m, 1H).

Workup

  1. concentrationthe mixture was concentrated
  2. dissolutionthe residue was dissolved in EtOAc
  3. washwashed with H2O
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customThe resulting residue was purified by basic reverse phase HPLC

Sources & evidence

ORD record
ord-cc8f413fa95a4ac9a0330f9e608a5d57
Source dataset
uspto-grants-2012_08
Patent number
US08242275B2

Reaction notes

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