Ethoxyacetic acid → HCID 10010071, compound

HRID 1198711Notes

Reaction equation

HRID 1198711 reaction equation
[CH2:1]([O:3][CH2:4][C:5]([OH:7])=O)[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.[NH2:20][C:21]1[CH:22]=[CH:23][C:24]([Cl:62])=[C:25]([N:27]2[C:31](=[O:32])[N:30]([CH2:33][C:34]3[CH:39]=[CH:38][C:37]([C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=4[S:46](=[O:56])(=[O:55])[NH:47][C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])=[CH:36][C:35]=3[F:57])[C:29]([CH2:58][CH2:59][CH2:60][CH3:61])=[N:28]2)[CH:26]=1.N12CCCN=C1CCCCC2>C1COCC1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[C:51]([O:50][C:48]([NH:47][S:46]([C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][C:40]=1[C:37]1[CH:38]=[CH:39][C:34]([CH2:33][N:30]2[C:29]([CH2:58][CH2:59][CH2:60][CH3:61])=[N:28][N:27]([C:25]3[CH:26]=[C:21]([NH:20][C:5](=[O:7])[CH2:4][O:3][CH2:1][CH3:2])[CH:22]=[CH:23][C:24]=3[Cl:62])[C:31]2=[O:32])=[C:35]([F:57])[CH:36]=1)(=[O:55])=[O:56])=[O:49])([CH3:52])([CH3:53])[CH3:54]

Participants

7

Reactant 4

HCID 12301Ethoxyacetic acidHCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 10258462HCID 10258462, compound

Product 1

HCID 10010071HCID 10010071, compoundYield 20%

Reagents, catalysts & solvents 2

HCID 311Citric AcidSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

A mixture of 12 μL (13.2 mg, 0.127 mmol) of ethoxyacetic acid, 20.6 mg (0.127 mmol) of 1,1'-carbonyldiimidazole (CDI), and 1 mL of dry THF was stirred at 60° C. for 4 hours. To this solution was then added 40 mg (0.0635 mmol) of 2-(5-amino2-chlorophenyl)-4-[[2'-[N-(t-butoxycarbonyl)sulfamoyl]-3-fluorobiphenyl-4-yl]methyl]-5-n-butyl-2,4-dihydro-3H-1,2,4-triazol-3-one (from Step C) dissolved in THF, followed by 19 μL (19.3 mg, 0.127 mmol) of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). After being stirred overnight at 60° C., the reaction mixture was diluted with 5% citric acid (aqueous) and extracted 2× with ethyl acetate. The combined organic fractions were washed twice with water, then with brine, and dried over Na2SO4. The filtered solution was concentrated, and the residue was flash chromatographed on silica gel (gradient elution with 0.5-2% MeOH in CH2Cl2), yielding 9 mg (20%) of the title compound as a white, glassy solid, mp 100°-102° C.; satisfactory purity by TLC in 95:5 CH2Cl2 --MeOH; mass spectrum (FAB) m/e 622 (M+Li)+.

Workup

  1. stirringAfter being stirred overnight at 60° C.
  2. extractionextracted 2× with ethyl acetate
  3. washThe combined organic fractions were washed twice with water
  4. dry with materialwith brine, and dried over Na2SO4
  5. concentrationThe filtered solution was concentrated
  6. customchromatographed on silica gel (gradient elution with 0.5-2% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-c71ad5b33d104ba9986c9c7b362d052e
Source dataset
uspto-grants-1994_01
Patent number
US05281614

Reaction notes

Loading…