HOAt → HCID 67288081, compound

HRID 1626502Notes

Reaction equation

HRID 1626502 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][C:13]1[CH:21]=[CH:20][C:16]([C:17]([OH:19])=O)=[CH:15][CH:14]=1)[O:8][CH2:7][CH2:6][CH:5]2[C:22]([O:24][CH2:25][CH3:26])=[O:23].[F:27][C:28]1[CH:29]=[C:30]([N:35]2[CH:39]=[CH:38][C:37]([NH2:40])=[N:36]2)[CH:31]=[CH:32][C:33]=1[F:34].N1C2C(=NC=CC=2)N(O)N=1.Cl.CN(C)CCCN=C=NCC>CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][C:13]1[CH:14]=[CH:15][C:16]([C:17](=[O:19])[NH:40][C:37]3[CH:38]=[CH:39][N:35]([C:30]4[CH:31]=[CH:32][C:33]([F:34])=[C:28]([F:27])[CH:29]=4)[N:36]=3)=[CH:20][CH:21]=1)[O:8][CH2:7][CH2:6][CH:5]2[C:22]([O:24][CH2:25][CH3:26])=[O:23]

Participants

7

Reactant 4

HCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 582443954-(6-Chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acidHCID 67287673HCID 67287673, compound

Product 1

HCID 67288081HCID 67288081, compoundYield 92.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(6-chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid (0.050 g, 0.13 mmol), 1-(3,4-difluorophenyl)-1H-pyrazol-3-amine (0.028 g, 0.15 mmol), and 3H-[1,2,3]triazolo[4,5-b]pyridin-3-ol (0.018 g, 0.13 mmol) in DMF (0.7 ml) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.028 g, 0.15 mmol), and the reaction was allowed to stir at ambient temperature for 60 hours. The reaction was diluted with EtOAc and washed with 10% citric acid, saturated sodium bicarbonate, and saturated sodium chloride. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography, eluting with a linear gradient of 5-70% EtOAc/hexanes to yield the desired product (0.067 g, 0.12 mmol, 91% yield).

Workup

  1. washwashed with 10% citric acid, saturated sodium bicarbonate, and saturated sodium chloride
  2. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel chromatography
  6. washeluting with a linear gradient of 5-70% EtOAc/hexanes

Sources & evidence

ORD record
ord-6869f2cf708d414e86dc7b4cbbf6c32c
Source dataset
uspto-grants-2014_07
Patent number
US08785445B2

Reaction notes

Loading…