Hydrochloric Acid → HCID 68816641, compound

HRID 734350Notes

Reaction equation

HRID 734350 reaction equation
[ClH:1].[C:2]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][CH:13]([C:16]([N:18]3[CH2:23][C@H:22]([CH3:24])[NH:21][C@H:20]([CH3:25])[CH2:19]3)=[O:17])[CH2:12][CH2:11]2)=[CH:6][CH:5]=1)#[N:3].[C:26]1(=O)[CH2:29][CH2:28][CH2:27]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl>C(Cl)Cl>[ClH:1].[CH:26]1([N:21]2[C@@H:20]([CH3:25])[CH2:19][N:18]([C:16]([CH:13]3[CH2:14][CH2:15][N:10]([C:7]4[CH:6]=[CH:5][C:4]([C:2]#[N:3])=[CH:9][CH:8]=4)[CH2:11][CH2:12]3)=[O:17])[CH2:23][C@H:22]2[CH3:24])[CH2:29][CH2:28][CH2:27]1

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 14496CyclobutanoneHCID 5049666Sodium triacetoxyborohydrideHCID 68816962799559-60-7

Product 1

HCID 68816641HCID 68816641, compoundYield 15.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

(2R,6S)-4-[1-(4-Cyanophenyl)-piperidine-4-carbonyl]-2,6-dimethylpiperazine hydrochloride (D13)(0.30 g), TEA (0.4 ml), cyclobutanone (0.13 g) and sodium triacetoxyborohydride (0.40 g) in DCM (5 ml) were heated to 100° C. in a microwave reactor for 5 min. The reaction mixture was then washed with saturated potassium carbonate solution (2×30 ml), and brine (30 ml). The organic layer was then dried (MgSO4) and evaporated give the crude product which was purified by column chromatography [silica gel, step gradient 0-10% MeOH (containing 10% 0.880 ammonia solution) in DCM]. Fractions containing the required product were evaporated to give the free base compound which was converted to the HCl salt by redissolving in DCM and then treating with excess hydrogen chloride (1 M solution in diethyl ether), evaporating and then crystallising from acetone to give the title compound (E33) as a pale grey solid (0.053 g). MS electrospray (+ve) 381 (MH+). 1H NMR δ [DMSO-d6]: 11.28 plus 10.10 (1H, m, rotomers), 7.59 (2H, d, J=8.4 Hz), 7.00 (2H, d, J=8.OHz), 4.31-3.73 (6H, m), 3.60-3.22 (3H, m), 2.97 (3H, m), 2.50-2.08 (4H, m), 1.78-1.61 (6H, m), 1.50-1.10 (6H, m).

Workup

  1. washThe reaction mixture was then washed with saturated potassium carbonate solution (2×30 ml), and brine (30 ml)
  2. dry with materialThe organic layer was then dried (MgSO4)
  3. customevaporated
  4. customgive the crude product which
  5. customwas purified by column chromatography [silica gel, step gradient 0-10% MeOH (containing 10% 0.880 ammonia solution) in DCM]
  6. additionFractions containing the required product
  7. customwere evaporated
  8. customto give the free base compound which
  9. customevaporating
  10. customcrystallising from acetone

Sources & evidence

ORD record
ord-1a61ab733c634c358e82fdc37811e482
Source dataset
uspto-grants-2009_09
Patent number
US07592347B2

Reaction notes

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