1,2-Dichloroethane → HCID 66635613, compound

HRID 2204759Notes

Reaction equation

HRID 2204759 reaction equation
[N:1]1([C:7]([C:9]2[C:24]([C:25]([F:28])([F:27])[F:26])=[CH:23][C:12]([C:13]([O:15]CC3C=CC=CC=3)=O)=[C:11]([O:29][CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH:10]=2)=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[OH-].[Li+].Cl.C(N(C(C)C)CC)(C)C.[N:49]1[CH:54]=[CH:53][C:52]([NH2:55])=[CH:51][N:50]=1.ON1C2N=CC=CC=2N=N1.C(Cl)CCl>O1CCCC1.CN(C)C=O.O.C(OCC)(=O)C>[N:1]1([C:7]([C:9]2[C:24]([C:25]([F:26])([F:28])[F:27])=[CH:23][C:12]([C:13]([NH:55][C:52]3[CH:53]=[CH:54][N:49]=[N:50][CH:51]=3)=[O:15])=[C:11]([O:29][CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH:10]=2)=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1

Participants

12

Reactant 7

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 2984924-AminopyridazineHCID 66611389HCID 66611389, compound

Product 1

HCID 66635613HCID 66635613, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of phenylmethyl 4-(4-morpholinylcarbonyl)-2-[(phenylmethyl)oxy]-5-(trifluoromethyl)benzoate (may be prepared as described in Description 56; 80 mg, 0.16 mmol) in tetrahydrofuran (4 ml) was added lithium hydroxide (11.51 mg, 0.48 mmol) and water (1 ml). The mixture was heated at 45° C. for one hour, cooled and 2M hydrochloric acid (0.24 ml, 0.48 mmol) was added. The solvent was removed in vacuo to give a residue. The residue was redissolved in N,N-dimethylformamide (4 ml) and diisopropylethylamine (0.06 ml, 0.32 mmol), 4-pyridazinamine (19.80 mg, 0.21 mmol), 1-hydroxy-7-azabenzotriazole (28.3 mg, 0.21 mmol) and EDC (55.3 mg, 0.29 mmol) were added. The mixture was stirred for 72 hours. Ethyl acetate (10 ml) and water (10 ml) were added and the organic layer separated and washed further with water (10 ml), dried (MgSO4) and the solvent removed in vacuo to give a gum. Purification by MDAP gave the title compound as a white solid. 30 mg.

Workup

  1. temperaturecooled
  2. customThe solvent was removed in vacuo
  3. customto give a residue
  4. customthe organic layer separated
  5. washwashed further with water (10 ml)
  6. dry with materialdried (MgSO4)
  7. customthe solvent removed in vacuo
  8. customto give a gum
  9. customPurification by MDAP

Sources & evidence

ORD record
ord-508af106f9e54d9fa0b670195bdb1c60
Source dataset
uspto-grants-2016_06
Patent number
US09365551B2

Reaction notes

Loading…