Hydrochloric Acid → HCID 68817954, compound

HRID 734351Notes

Reaction equation

HRID 734351 reaction equation
[ClH:1].[C:2]([C:4]1[CH:5]=[CH:6][C:7]([N:10]2[CH2:15][CH2:14][CH:13]([C:16]([N:18]3[CH2:24][CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)=[O:17])[CH2:12][CH2:11]2)=[N:8][CH:9]=1)#[N:3].[C:25]1(=O)[CH2:28][CH2:27][CH2:26]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl>C(Cl)Cl>[ClH:1].[CH:25]1([N:21]2[CH2:22][CH2:23][CH2:24][N:18]([C:16]([CH:13]3[CH2:12][CH2:11][N:10]([C:7]4[CH:6]=[CH:5][C:4]([C:2]#[N:3])=[CH:9][N:8]=4)[CH2:15][CH2:14]3)=[O:17])[CH2:19][CH2:20]2)[CH2:28][CH2:27][CH2:26]1

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 14496CyclobutanoneHCID 5049666Sodium triacetoxyborohydrideHCID 68816413HCID 68816413, compound

Product 1

HCID 68817954HCID 68817954, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

1-[1-(5-Cyanopyridin-2-yl)-piperidine-4-carbonyl]-[1,4]-diazepane hydrochloride (D14) (0.30 g) was dissolved in DCM (10 ml) and TEA (0.4 ml) was added followed by cyclobutanone (0.14 ml). The reaction was stirred for 5 min under argon and then sodium triacetoxyborohydride (0.41 g) was added and the reaction stirred at rt for 4 h. The reaction mixture was washed with saturated aqueous potassium carbonate (2×30 ml), saturated sodium hydrogen carbonate (2×50 ml) and brine (50 ml). The organic layer was then dried (MgSO4) and evaporated to a crude which was purified by column chromatography [silica gel, step gradient 0-10% MeOH (containing 10% 0.880 ammonia solution) in DCM] to give the free base product which was converted to the HCl salt by redissolving in DCM and then treating with excess hydrogen chloride (1M solution in diethyl ether) and concentrating to yield the title compound (E37) as a pale yellow solid (0.047 g). MS electrospray (+ve) 368 (MH+). 1H NMR δ [DMSO-d6]: 10.80-10.50 (1H, m), 8.47 (1H, s), 7.83 (1H, d, J=8.8 Hz), 6.95 (2H, d, J=8.8 Hz), 4.44 (2H, m), 4.05 (1H, m), 3.85-3.28 (6H, m), 3.07-2.72 (5H, m), 2.41-2.01 (6H, m), 1.82-1.41 (6H, m).

Workup

  1. stirringthe reaction stirred at rt for 4 h
  2. washThe reaction mixture was washed with saturated aqueous potassium carbonate (2×30 ml), saturated sodium hydrogen carbonate (2×50 ml) and brine (50 ml)
  3. dry with materialThe organic layer was then dried (MgSO4)
  4. customevaporated to a crude which
  5. customwas purified by column chromatography [silica gel, step gradient 0-10% MeOH (containing 10% 0.880 ammonia solution) in DCM]
  6. customto give the free base product which
  7. concentrationconcentrating

Sources & evidence

ORD record
ord-8b039ab33ec5447ea249a974d5441522
Source dataset
uspto-grants-2009_09
Patent number
US07592347B2

Reaction notes

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