Triethylamine → HCID 58949536, compound

HRID 1676405Notes

Reaction equation

HRID 1676405 reaction equation
[F:1][C:2]1[CH:20]=[C:19]([NH:21][C:22]([C:24]2[C:25](=[O:37])[N:26]([C:30]3[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=3)[N:27]=[CH:28][CH:29]=2)=[O:23])[CH:18]=[CH:17][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[CH:11]=C(C(O)=O)[S:13][C:6]=12.CCN=C=NCCC[N:46]([CH3:48])C.C1C=CC2N([OH:58])N=NC=2C=1.CN1CCNCC1.[CH3:66][CH2:67][N:68]([CH2:71][CH3:72])[CH2:69][CH3:70]>CN(C=O)C.CCOC(C)=O>[F:1][C:2]1[CH:20]=[C:19]([NH:21][C:22]([C:24]2[C:25](=[O:37])[N:26]([C:30]3[CH:31]=[CH:32][C:33]([F:36])=[CH:34][CH:35]=3)[N:27]=[CH:28][CH:29]=2)=[O:23])[CH:18]=[CH:17][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[CH:11]=[C:66]([C:67]([N:68]3[CH2:71][CH2:72][N:46]([CH3:48])[CH2:70][CH2:69]3)=[O:58])[S:13][C:6]=12

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 531671-MethylpiperazineHCID 757711-HydroxybenzotriazoleHCID 67348692HCID 67348692, compound

Product 1

HCID 58949536HCID 58949536, compoundYield 79.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 7-(2-fluoro-4-(2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamido)phenoxy)thieno[3,2-b]pyridine-2-carboxylic acid (12 mg, 0.023 mmol), EDCI (13.3 mg, 0.069 mmol), and HOBt (9.4 mg, 0.069 mmol) in DMF (1 mL) was stirred at room temperature for 30 minutes. 1-Methylpiperazine (6.9 mg, 0.069 mmol) was added followed by Et3N (7 mg, 0.069 mmol). After stirring for 2 hours, the reaction mixture was diluted with EtOAc and washed with saturated aqueous NH4Cl, saturated aqueous NaHCO3, and brine. The organic layer was dried over MgSO4 and concentrated under reduced pressure to give the crude material that was purified by silica gel flash column chromatography (5% MeOH in CH2Cl2) to afford 11 mg (79%) of the desired product. LRMS (APCI pos) m/e 603.3 (M+1). 1H-NMR (400 MHz, CD3OD) δ 8.87 (d, 1H), 8.37 (d, 1H), 8.32 (d, 1H), 8.14 (d, 1H), 8.03 (s, 1H), 7.68 (m, 2H), 7.57 (m, 2H), 7.24-7.32 (m, 3H), 3.61 (m, 4H), 2.98 (s, 3H); 19F-NMR (376 MHz, CD3OD) δ −114.7, −129.3.

Workup

  1. stirringAfter stirring for 2 hours
  2. washwashed with saturated aqueous NH4Cl, saturated aqueous NaHCO3, and brine
  3. dry with materialThe organic layer was dried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customto give the crude material that
  6. customwas purified by silica gel flash column chromatography (5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-00d6bd139ac54e7296729ff438b09e15
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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