Potassium Carbonate → HCID 46209554, compound

HRID 2106129Notes

Reaction equation

HRID 2106129 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:22][C:23](=[O:35])[C:24]([NH:26][CH2:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[O:25])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([OH:21])=[C:16]([O:19][CH3:20])[CH:17]=2)[N:12]=[CH:11][CH:10]=1.Cl.Cl[CH2:38][CH2:39][CH2:40][N:41]1[CH2:46][CH2:45][O:44][CH2:43][CH2:42]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([NH:22][C:23](=[O:35])[C:24]([NH:26][CH2:27][CH2:28][C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)=[O:25])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([O:21][CH2:38][CH2:39][CH2:40][N:41]3[CH2:46][CH2:45][O:44][CH2:43][CH2:42]3)=[C:16]([O:19][CH3:20])[CH:17]=2)[N:12]=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 122962834-(3-Chloropropyl)morpholinium chlorideHCID 136168658HCID 136168658, compound

Product 1

HCID 46209554HCID 46209554, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of N-{3-fluoro-4-[(7-hydroxy-6-methoxyquinolin-4-yl)oxy]phenyl}-N′-(2-phenylethyl)ethanediamide (25.6 g, 54 mmol), N-(3-chloropropyl)morpholine hydrochloride (11.7 g, 592 mmol) and potassium carbonate (16.6 g, 120 mmol) in DMF (300 mL) was heated to 80° C. overnight. Upon cooling, a majority of the DMF (250 mL) was removed on a rotary evaporator, 5% aqueous LiCl (300 mL) was added and the mixture was sonicated at room temperature. The solid was filtered, suspended in 1N HCl and washed with ethyl acetate (2×300 mL). The solution was adjusted to pH 14 using 2N sodium hydroxide and subsequently extracted with dichloromethane (3×200 mL). The organic layer was dried over sodium sulfate, filtered and evaporated to give N-(3-fluoro-4-{[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxy}phenyl)-N′-(2-phenylethyl)ethanediamide as a yellow solid (24 g, 74%). 1H NMR (400 MHz, CDCl3): δ 9.37 (s, 1H), 8.46 (d, 1H), 7.81 (dd, 1H), 7.57 (t, 1H), 7.53 (s, 1H), 7.42 (s, 2H), 7.34-7.20 (m, 6H), 6.39 (d, 1H), 4.27 (t, 2H), 4.03 (s, 3H), 3.71 (m, 4H), 3.65 (q, 2H), 2.91 (t, 2H), 2.56 (br s, 4H), 2.13 (m, 2H); 13C NMR (100 MHz, d6-DMSO): δ 160.1, 160.0, 159.5, 155.2, 152.7, 152.6, 150.2, 149.5, 147.1, 139.7, 137.3, 137.1, 129.3, 129.1, 126.9, 124.8, 117.9, 115.1, 109.2, 102.7, 99.6, 67.4, 66.9, 56.5, 55.5, 54.1, 41.3, 35.2, 26.4; IR (cm−1): 1655, 1506, 1483, 1431, 1350, 1302, 1248, 1221, 1176, 1119, 864, 843, 804, 741, 700; LC/MS (M+H=603).

Workup

  1. temperatureUpon cooling
  2. customa majority of the DMF (250 mL) was removed on a rotary evaporator, 5% aqueous LiCl (300 mL)
  3. additionwas added
  4. customthe mixture was sonicated at room temperature
  5. filtrationThe solid was filtered
  6. washwashed with ethyl acetate (2×300 mL)
  7. extractionsubsequently extracted with dichloromethane (3×200 mL)
  8. dry with materialThe organic layer was dried over sodium sulfate
  9. filtrationfiltered
  10. customevaporated

Sources & evidence

ORD record
ord-ebfe497fb9774e7db249b3e970d2149b
Source dataset
uspto-grants-2009_08
Patent number
US07579473B2

Reaction notes

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