Potassium Carbonate → 8-(1-cyclopropyl-6-fluoro-1H-benzimidazol-2-yl)-1,6-naphthyridine

HRID 1048947Notes

Reaction equation

HRID 1048947 reaction equation
[CH:1]1([NH:4][C:5]2[C:6]([NH2:12])=[CH:7][CH:8]=[C:9]([F:11])[CH:10]=2)[CH2:3][CH2:2]1.[N:13]1[C:22]2[C:17](=[CH:18][N:19]=[CH:20][C:21]=2[CH:23]=O)[CH:16]=[CH:15][CH:14]=1.OOS([O-])=O.[K+].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O.C(OCC)(=O)C>[CH:1]1([N:4]2[C:5]3[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:6]=3[N:12]=[C:23]2[C:21]2[CH:20]=[N:19][CH:18]=[C:17]3[C:22]=2[N:13]=[CH:14][CH:15]=[CH:16]3)[CH2:3][CH2:2]1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 23707502Potassium hydroxy sulfiteHCID 534219291,6-Naphthyridine-8-carbaldehydeHCID 545925541-N-cyclopropyl-5-fluorobenzene-1,2-diamine

Product 1

HCID 566453598-(1-cyclopropyl-6-fluoro-1H-benzimidazol-2-yl)-1,6-naphthyridine

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of N2-cyclopropyl-4-fluorobenzene-1,2-diamine (0.080 g, 0.48 mmol) in DMF (1.17 mL) and water (0.04 mL) were added the title compound from Example 8 Step A (0.084 g, 0.53 mmol) and OXONE® (0.192 g, 0.313 mmol). The resulting mixture was stirred at room temperature for 1 hour, then diluted with ethyl acetate and water. Solid potassium carbonate was added until the aqueous layer was basic (pH ˜9). Ethyl acetate was added, and the organic layer was separated, washed with water and brine, dried over magnesium sulfate, filtered and concentrated. Purification by flash chromatography on silica gel (50% ethyl acetate in hexanes, then 100% ethyl acetate) provided the title compound: LCMS m/z 304.99 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 9.09 (s, 1 H), 9.13 (m, 1 H), 9.07 (s, 1 H), 8.43 (d, J=8.3 Hz, 1 H), 7.78 (dd, J=8.7, 4.8 Hz, 1 H), 7.63 (dd, J=8.2, 4.2 Hz, 1 H), 7.34 (dd, J=8.7, 2.2 Hz, 1 H), 7.07 (m, 1 H), 3.55-3.53 (m, 1 H), 0.62-0.61 (m, 4 H).

Workup

  1. customthe organic layer was separated
  2. washwashed with water and brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by flash chromatography on silica gel (50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-eca0fbf5738847e48ee478121c018bbf
Source dataset
uspto-grants-2016_07
Patent number
US09382226B2

Reaction notes

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