Hydrochloric Acid → 6-{2-{[4-(2-Cyclopropylaminoethoxy)benzyl]isopropylamino}-4-methoxyphenyl}-5,6,7,8-tetrahydronaphthalen-2-ol

HRID 1950476Notes

Reaction equation

HRID 1950476 reaction equation
[OH:1][C:2]1[CH:38]=[CH:37][C:5]([C:6]([N:8]([CH:34]([CH3:36])[CH3:35])[C:9]2[CH:14]=[C:13]([O:15][CH3:16])[CH:12]=[CH:11][C:10]=2[CH:17]2[CH2:26][CH2:25][C:24]3[CH:23]=[C:22]([O:27]C(=O)C(C)(C)C)[CH:21]=[CH:20][C:19]=3[CH2:18]2)=O)=[CH:4][CH:3]=1.Cl[CH2:40][C:41]([NH:43][CH:44]1[CH2:46][CH2:45]1)=O.C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[K+].B.O1CCCC1.Cl.[OH-].[Na+]>O.O1CCCC1>[CH:44]1([NH:43][CH2:41][CH2:40][O:1][C:2]2[CH:3]=[CH:4][C:5]([CH2:6][N:8]([CH:34]([CH3:36])[CH3:35])[C:9]3[CH:14]=[C:13]([O:15][CH3:16])[CH:12]=[CH:11][C:10]=3[CH:17]3[CH2:26][CH2:25][C:24]4[CH:23]=[C:22]([OH:27])[CH:21]=[CH:20][C:19]=4[CH2:18]3)=[CH:37][CH:38]=2)[CH2:46][CH2:45]1

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 4875Potassium IodideHCID 10796Cesium carbonateHCID 14798Sodium HydroxideHCID 7357802-chloro-N-cyclopropylacetamideHCID 2723981Borane;tetrahydrofuranHCID 57933955Pivalic acid 6-{2-[(4-hydroxybenzoyl)isopropylamino]-4-methoxyphenyl}-5,6,7,8-tetrahydronaphthalen-2-yl ester

Product 1

HCID 579345306-{2-{[4-(2-Cyclopropylaminoethoxy)benzyl]isopropylamino}-4-methoxyphenyl}-5,6,7,8-tetrahydronaphthalen-2-olYield 37.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of pivalic acid 6-{2-[(4-hydroxybenzoyl)isopropylamino]-4-methoxyphenyl}-5,6,7,8-tetrahydronaphthalen-2-yl ester (25 mg), 2-chloro-N-cyclopropylacetamide (13 mg), cesium carbonate (32 mg), potassium iodide (5.0 mg) and tetrahydrofuran (2 ml) was stirred for 5 hours at 60° C. To the reaction solution was added dropwise borane-tetrahydrofuran complex (1.0 M solution in tetrahydrofuran) (0.49 ml), and the solution was stirred at 60° C. for one day and one night. The reaction solution was cooled to room temperature, concentrated hydrochloric acid (0.08 ml) was added thereto, the solution was stirred for 1.5 hours at 60° C., then an aqueous solution of 5N sodium hydroxide (1 ml) was added thereto, and the solution was stirred for 8 hours at 60° C. The reaction solution was diluted with water, then extracted with ethyl acetate. The organic layer was concentrated under a nitrogen stream; purified from a solution of the resulting residue in N,N-dimethylformamide by LC-MS, the title compound (9.0 mg) was obtained.

Workup

  1. stirringthe solution was stirred at 60° C. for one day and one night
  2. temperatureThe reaction solution was cooled to room temperature
  3. stirringthe solution was stirred for 1.5 hours at 60° C.
  4. stirringthe solution was stirred for 8 hours at 60° C
  5. extractionextracted with ethyl acetate
  6. concentrationThe organic layer was concentrated under a nitrogen stream
  7. custompurified from a solution of the resulting residue in N,N-dimethylformamide by LC-MS

Sources & evidence

ORD record
ord-965f23b897b949e092036caf39ccb323
Source dataset
uspto-grants-2013_03
Patent number
US08399520B2

Reaction notes

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