Water → 4-amino-8-(4-methoxy-3-pyridyl)-N-propyl-cinnoline-3-carboxamide

HRID 2375621Notes

Reaction equation

HRID 2375621 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[C:7](I)[CH:8]=[CH:9][CH:10]=2)[N:5]=[N:4][C:3]=1[C:13]([NH:15][CH2:16][CH2:17][CH3:18])=[O:14].C(=O)(O)[O-].[Na+].O.[CH3:25][O:26][C:27]1[CH:32]=[CH:31][N:30]=[CH:29][C:28]=1B(O)O>COCCOC.C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:1][C:2]1[C:11]2[C:6](=[C:7]([C:28]3[CH:29]=[N:30][CH:31]=[CH:32][C:27]=3[O:26][CH3:25])[CH:8]=[CH:9][CH:10]=2)[N:5]=[N:4][C:3]=1[C:13]([NH:15][CH2:16][CH2:17][CH3:18])=[O:14]

Participants

8

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 27625564-Methoxypyridine-3-boronic acid2×HCID 140123274-amino-8-iodo-N-propyl-cinnoline-3-carboxamide

Product 1

HCID 236300654-amino-8-(4-methoxy-3-pyridyl)-N-propyl-cinnoline-3-carboxamideYield 60.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a stirred solution of 4-amino-8-iodo-N-propyl-cinnoline-3-carboxamide (1.00 g, 2.81 mmol), sodium bicarbonate (473 mg, 5.62 mmol) and tetrakis(triphenylphosphine)palladium(0) (974 mg, 0.84 mmol) in 1,2-dimethoxyethane (180 mL)/water (30 mL) at 85° C. under nitrogen was added the aqueous solution of 4-methoxy-pyridine-3-boronic acid (25 mg/mL) dropwise, maintaining the internal temperature between 80° C. and 85° C. The reaction was monitored by HPLC until completed. Upon the completion, 2.42 equivalents of 4-methoxy-pyridine-3-boronic acid (1.16 g, 6.80 mmol) were applied. The reaction mixture was diluted with methylene chloride (300 mL), washed with water twice, dried through MgSO4, and then the solvent was evaporated. The residual was purified by flash chromatography using a gradient of methanol in methylene chloride to give a yellow solid. The yellow solid was crystallized from methylene chloride/methanol (2/1) to give an off-white needle crystal as the title compound (570 mg, 60.2% yield). 1H NMR (300 MHz, CDCl3) δ 8.58 (d, J=5.8 Hz, 1H), 8.53 (br, 1H), 5.11 (m, 6H), 8.46 (s, 1H), 7.94 (t, J=4.9 Hz, 1H), 7.74 (d, J=4.8 Hz, 2H), 6.96 (d, J=5.8 Hz, 1H), 3.78 (s, 3H), 3.45 (q, J=6.7 Hz, 2H), 1.66 (m, overlapped with H2O), 1.00 (t, J=7.4 Hz, 3H) MS APCI, m/z=338 (M+H) HPLC 1.28 min.

Workup

  1. temperaturemaintaining the internal temperature between 80° C. and 85° C
  2. washwashed with water twice
  3. dry with materialdried through MgSO4
  4. customthe solvent was evaporated
  5. customThe residual was purified by flash chromatography
  6. customto give a yellow solid
  7. customThe yellow solid was crystallized from methylene chloride/methanol (2/1)

Sources & evidence

ORD record
ord-469a8644952e4754bf9ca486b37a5af7
Source dataset
uspto-grants-2008_12
Patent number
US07465795B2

Reaction notes

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