Hydrochloric Acid → {3'-[4-(1-Ethyl-1H-pyrazol-4-ylmethyl)-piperazin-1-yl]-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-yl}-methanol hydrochloride

HRID 604316Notes

Reaction equation

HRID 604316 reaction equation
[N:1]1([C:7]2[C:8]([N:13]3[CH2:18][CH2:17][CH:16]([CH2:19][OH:20])[CH2:15][CH2:14]3)=[N:9][CH:10]=[CH:11][CH:12]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[CH2:21]([N:23]1[CH:27]=[C:26]([CH:28]=O)[CH:25]=[N:24]1)[CH3:22].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+].[ClH:46]>ClCCCl.C(#N)C.C(Cl)Cl>[ClH:46].[CH2:21]([N:23]1[CH:27]=[C:26]([CH2:28][N:4]2[CH2:3][CH2:2][N:1]([C:7]3[C:8]([N:13]4[CH2:14][CH2:15][CH:16]([CH2:19][OH:20])[CH2:17][CH2:18]4)=[N:9][CH:10]=[CH:11][CH:12]=3)[CH2:6][CH2:5]2)[CH:25]=[N:24]1)[CH3:22]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 27589001-Ethyl-1H-pyrazole-4-carboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 59438214(3'-piperazin-1-yl-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-yl)-methanol

Product 1

HCID 67038358{3'-[4-(1-Ethyl-1H-pyrazol-4-ylmethyl)-piperazin-1-yl]-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-yl}-methanol hydrochlorideYield 97.3%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (3′-piperazin-1-yl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-yl)-methanol (0.145 g, 0.524 mmol, 1 eq) and 1-ethyl-1H-pyrazole-4-carbaldehyde (97.69 mg, 0.787 mmol, 1.5 eq) in 1,2-dichloroethane (10 mL) add sodium triacetoxyborohydride (166.79 mg, 0.787 mmol, 1.5 eq) in one portion as a solid. Stir the mixture at room temperature under nitrogen for 20 hr. Add 2 M aqueous sodium hydroxide solution (20 ml) and DCM (20 ml). Separate using a phase separator and extract the aqueous layer with DCM (10 ml). Concentrate the combined organic extracts and purify by high pH reverse phase HPLC. Dissolve this material (120 mg, 0.31 mmol) in the minimum quantity of 50% aqueous acetonitrile. Add 2 M aqueous hydrogen chloride (155 μL, 0.31 mmol) and lyophilize to give the title compound (127 mg, 58%). MS (m/z): 385.2 (M+1).

Workup

  1. customSeparate
  2. extractionextract the aqueous layer with DCM (10 ml)
  3. concentrationConcentrate the combined organic extracts
  4. custompurify by high pH reverse phase HPLC

Sources & evidence

ORD record
ord-e96090f8338c4161a4926bd870298725
Source dataset
uspto-grants-2011_03
Patent number
US07910588B2

Reaction notes

Loading…