Diethylethanolamine → HCID 57810058, compound

HRID 2106113Notes

Reaction equation

HRID 2106113 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2([C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]4[C:33]5[C:28](=[CH:29][C:30]([OH:36])=[C:31]([O:34][CH3:35])[CH:32]=5)[N:27]=[CH:26][CH:25]=4)=[C:19]([F:37])[CH:18]=3)=[O:15])[CH2:13][CH2:12]2)=[O:10])=[CH:4][CH:3]=1.[CH2:38]([N:40]([CH2:44][CH3:45])[CH2:41][CH2:42]O)[CH3:39].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C(Cl)Cl>[CH2:38]([N:40]([CH2:44][CH3:45])[CH2:41][CH2:42][O:36][C:30]1[CH:29]=[C:28]2[C:33]([C:24]([O:23][C:20]3[CH:21]=[CH:22][C:17]([NH:16][C:14]([C:11]4([C:9]([NH:8][C:5]5[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=5)=[O:10])[CH2:12][CH2:13]4)=[O:15])=[CH:18][C:19]=3[F:37])=[CH:25][CH:26]=[N:27]2)=[CH:32][C:31]=1[O:34][CH3:35])[CH3:39]

Participants

6

Reactant 4

HCID 7497DiethylethanolamineHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 136168657N-(3-Fluoro-4-((7-hydroxy-6-methoxyquinolin-4-yl)oxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

Product 1

HCID 57810058HCID 57810058, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of cyclopropane-1,1-dicarboxylic acid [3-fluoro-4-(7-hydroxy-6-methoxy-quinolin-4-yloxy)-phenyl]-amide(4-fluoro-phenyl)-amide (186 mg, 0.36 mmol) in CH2Cl2 (10 mL) was added 2-(diethylamino)ethanol (63 mg, 0.54 mmol), and PPh3 (141 mg, 0.54 mmol). DIAD (109 mg, 0.54 mmol) was then added as a CH2Cl2 (1 mL) solution. The resulted solution was stirred at room temperature for 2 h and the solvent was removed under reduced pressure. To the residue was added 1 N HCl (50 mL), and it was washed with EtOAc (50 mL×2). The aqueous phase was basified by adding 15% NaOH aqueous solution until pH=11-13, and then extracted with ether (50 mL×2). The combined organic layer was dried (MgSO4), and concentrated in vacuo. The residue was purified on preparative HPLC to give N-(4-{[7-{[2-(diethylamino)ethyl]oxy}-6-(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N′-(4-fluoro-phenyl)cyclopropane-1,1-dicarboxamide (74 mg, 34%) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 10.40 (br s, 1H), 10.02 (br s, 1H), 8.47 (d, J=5.2 Hz, 1H), 7.91 (br d, J=13.9 Hz, 1H), 7.54-7.52 (m, 2H), 7.55-7.50 (m, 1H), 7.52 (s, 1H), 7.50-7.40 (m, 1H), 7.41 (s, 1H), 7.16 (br t, J=8.7 Hz, 2H), 6.41 (br d, J=4.7 Hz, 1H), 4.18 (t, J=6.0 Hz, 2H), 3.94 (s, 3H), 2.87 (br t, J=6.3 Hz, 2H), 2.59 (q, J=7.1 Hz, 4H), 1.47 (br s, 4H), 1.00 (t, J=7.0 Hz, 6H).

Workup

  1. customthe solvent was removed under reduced pressure
  2. additionTo the residue was added 1 N HCl (50 mL), and it
  3. washwas washed with EtOAc (50 mL×2)
  4. additionby adding 15% NaOH aqueous solution until pH=11-13
  5. extractionextracted with ether (50 mL×2)
  6. dry with materialThe combined organic layer was dried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified on preparative HPLC

Sources & evidence

ORD record
ord-eb44356ec5484218b04e892f2cc88a39
Source dataset
uspto-grants-2009_08
Patent number
US07579473B2

Reaction notes

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