7-(Benzyloxy)-4-chloro-6-methoxyquinoline → N1-[3-Fluoro-4-[[6-methoxy-7-(phenylmethoxy)-4-quinolinyl]oxy]phenyl]-N2-(2-phenylethyl)ethanediamide

HRID 445479Notes

Reaction equation

HRID 445479 reaction equation
[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13](Cl)=[CH:14][CH:15]=[N:16]2)=[CH:11][C:10]=1[O:20][CH3:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:22][C:23]1[CH:24]=[C:25]([NH:30][C:31](=[O:43])[C:32]([NH:34][CH2:35][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[O:33])[CH:26]=[CH:27][C:28]=1[OH:29]>CN(C1C=CN=CC=1)C.BrC1C=CC=CC=1>[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([O:29][C:28]3[CH:27]=[CH:26][C:25]([NH:30][C:31](=[O:43])[C:32]([NH:34][CH2:35][CH2:36][C:37]4[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=4)=[O:33])=[CH:24][C:23]=3[F:22])=[CH:14][CH:15]=[N:16]2)=[CH:11][C:10]=1[O:20][CH3:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 226465627-(Benzyloxy)-4-chloro-6-methoxyquinolineHCID 57810404N-(3-fluoro-4-hydroxyphenyl)-N'-(2-phenylethyl)ethanediamide

Product 1

HCID 57810393N1-[3-Fluoro-4-[[6-methoxy-7-(phenylmethoxy)-4-quinolinyl]oxy]phenyl]-N2-(2-phenylethyl)ethanediamideYield 61%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 7961BromobenzeneSolvent

Procedure

A mixture of 7-benzyloxy-4-chloro-6-methoxyquinoline (30 g, 100 mmol), N-(3-fluoro-4-hydroxyphenyl)-N′-(2-phenylethyl)ethanediamide (32 g, 106 mmol), DMAP (125 g, 1.02 mol) and bromobenzene (500 mL) was heated to reflux for 6 h. The mixture was cooled to room temperature and the bromobenzene was removed under reduced pressure. Methanol (500 mL) was added to the residue and the mixture was stirred at room temperature for 2 h. The resulting solid was filtered, washed with methanol and dried to give N-{4-[(7-benzyloxy-6-methoxyquinolin-4-yl)oxy]-3-fluorophenyl}-N′-(2-phenylethyl)ethanediamide (34 g, 61%). 1H NMR (400 MHz, d6-DMSO): δ 11.05 (s, 1H), 9.15 (s, 1H), 8.47 (d, 1H), 8.05 (d, 1H), 7.84 (d, 1H), 7.56-6.36 (m, 13H), 6.46 (d, 1H), 5.32 (s, 2H), 3.97 (s, 3H), 3.47 (q, 2H), 2.86 (t, 2H); 13C NMR (100 MHz, d6-DMSO): δ 160.5, 160.2, 159.9, 159.5, 155.2, 152.7, 152.2, 150.3, 149.6, 146.9, 139.7, 137.4, 137.3, 137.2, 137.1, 129.3, 129.2, 129.1, 129.0, 128.9, 128.7, 128.6, 126.9, 124.8, 117.9, 115.3, 109.9, 102.8, 99.8, 70.6, 56.5, 41.3, 35.2; IR (cm−1): 1657, 1510, 1481, 1433, 1416, 1352, 1310, 1252, 1215, 1609, 986, 891, 868, 850, 742, 696; LC/MS (M+H=566).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 6 h
  3. customthe bromobenzene was removed under reduced pressure
  4. additionMethanol (500 mL) was added to the residue
  5. filtrationThe resulting solid was filtered
  6. washwashed with methanol
  7. customdried

Sources & evidence

ORD record
ord-8b19a622cfa84a45a693fe457a3b39f3
Source dataset
uspto-grants-2013_07
Patent number
US08476298B2

Reaction notes

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