Acetic Acid → N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-6-(isopropylamino)-1-benzothiophene-2-carboxamide dihydrochloride

HRID 335611Notes

Reaction equation

HRID 335611 reaction equation
[ClH:1].Cl.[NH2:3][C:4]1[CH:23]=[CH:22][C:7]2[CH:8]=[C:9]([C:11]([NH:13][C@@H:14]3[CH:19]4[CH2:20][CH2:21][N:16]([CH2:17][CH2:18]4)[CH2:15]3)=[O:12])[S:10][C:6]=2[CH:5]=1.[CH3:24][C:25]([CH3:27])=O.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[ClH:1].[ClH:1].[N:16]12[CH2:21][CH2:20][CH:19]([CH2:18][CH2:17]1)[C@@H:14]([NH:13][C:11]([C:9]1[S:10][C:6]3[CH:5]=[C:4]([NH:3][CH:25]([CH3:27])[CH3:24])[CH:23]=[CH:22][C:7]=3[CH:8]=1)=[O:12])[CH2:15]2

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 180AcetoneHCID 5049666Sodium triacetoxyborohydrideHCID 66904443HCID 66904443, compound

Product 1

HCID 68432768N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-6-(isopropylamino)-1-benzothiophene-2-carboxamide dihydrochloride

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution of 150 mg (0.40 mmol) of 6-amino-N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-1-benzothiophene-2-carboxamide dihydrochloride and 48 μl (0.65 mmol) of acetone in 1.5 ml of 1,2-dichloroethane is adjusted to pH 4 using acetic acid. 254.8 mg (1.20 mmol) of sodium triacetoxyborohydride are added, and the mixture is stirred at RT for 6 h. The contents of the flask are concentrated under reduced pressure and purified by preparative HPLC. The product fractions are concentrated and the residue is dissolved in a 5:1 mixture of acetonitrile and 1N hydrochloric acid, then again concentrated and dried under high vacuum. 49 mg (29.4% of theory) of the title compound are obtained.

Workup

  1. concentrationThe contents of the flask are concentrated under reduced pressure
  2. custompurified by preparative HPLC
  3. concentrationThe product fractions are concentrated
  4. dissolutionthe residue is dissolved in a 5:1 mixture of acetonitrile and 1N hydrochloric acid
  5. concentrationagain concentrated
  6. customdried under high vacuum

Sources & evidence

ORD record
ord-670bb79427b0430c90ea548b3d3e99a7
Source dataset
uspto-grants-2014_11
Patent number
US08884017B2

Reaction notes

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