Water → HCID 67179036, compound

HRID 1510059Notes

Reaction equation

HRID 1510059 reaction equation
[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][N:8]=[C:9]2[NH2:12])=[CH:4][CH:3]=1.[N:13]1[CH:18]=[CH:17][C:16]([C:19](=O)[CH2:20][C:21]([O:23]CC)=[O:22])=[CH:15][CH:14]=1.C([O-])(=[O:29])C.[NH4+].C1C=CC(C2C=CC=CC=2)=CC=1.C1C=CC(OC2C=CC=CC=2)=CC=1.Cl.C(O)(C)C.[OH2:62]>>[C:21]([OH:23])(=[O:22])[C:20]([OH:29])=[O:62].[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][N:8]3[C:21](=[O:22])[CH:20]=[C:19]([C:16]4[CH:17]=[CH:18][N:13]=[CH:14][CH:15]=4)[N:12]=[C:9]32)=[CH:4][CH:3]=1

Participants

7

Reactant 6

HCID 962WaterHCID 246701,1'-Biphenyl, mixt. with 1,1'-oxybis(benzene)HCID 517165Ammonium AcetateHCID 2735202Ethyl 3-(4-pyridyl)-3-oxopropionateHCID 21912024Isopropanol hydrochlorideHCID 226657347-Bromoisoquinolin-1-amine

Product 1

HCID 67179036HCID 67179036, compoundYield 30%

Conditions

Temperature
140 °C

Procedure

To a mixture of 0.1 g (0.38 mmol) of 7-bromoisoquinolin-1-amine (synthesis described in WO9847876) and 0.134 g (0.69 mmol) of ethyl 3-(4-pyridinyl)-3-oxopropionate were added 0.059 g (0.77 mmol) of ammonium acetate. The reaction mixture was heated at 140° C. for 12 hours. Then 2 ml of Dowtherm A were added and the resulting mixture was allowed to stir at 210° C. for 8 hours. After cooling, water was added and the resulting solution was acidified using isopropanol hydrochloride 6N. Dowtherm A was extracted using diethyl ether and the aqueous phase was basified by an aqueous solution of sodium hydroxide (30%) and extracted with dichloromethane. The extracts were dried over sodium sulphate and evaporated. The residue obtained was purified by chromatography on silica gel eluting with a mixture of dichloromethane/methanol in the proportions 99/1 to 95/5 to give 0.041 g (30%) of the desired compound which was transformed into the oxalate salt in the usual manner to give the pure product as a solid.

Workup

  1. temperatureAfter cooling
  2. extractionDowtherm A was extracted
  3. extractionextracted with dichloromethane
  4. dry with materialThe extracts were dried over sodium sulphate
  5. customevaporated
  6. customThe residue obtained
  7. customwas purified by chromatography on silica gel eluting with a mixture of dichloromethane/methanol in the proportions 99/1 to 95/5

Sources & evidence

ORD record
ord-72f55d8da9374a7fb689d7774793056f
Source dataset
uspto-grants-2012_07
Patent number
US08211903B2

Reaction notes

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