1-Methyl-4-piperidone → HCID 86718894, compound

HRID 528868Notes

Reaction equation

HRID 528868 reaction equation
[NH2:1][CH2:2][C@@H:3]1[CH2:12][C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][N:4]1[C:13]([C:15]1[CH:20]=[C:19]([C:21](=[O:36])[NH:22][S:23]([C:26]2[CH:35]=[CH:34][C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH:27]=2)(=[O:25])=[O:24])[CH:18]=[CH:17][C:16]=1[N:37]1[C:41]([CH3:42])=[C:40]([Cl:43])[C:39]([C:44]([N:46]([CH2:51][CH2:52][CH2:53][CH3:54])[CH2:47][CH2:48][CH2:49][CH3:50])=[O:45])=[N:38]1)=[O:14].[CH3:55][N:56]1[CH2:61][CH2:60][C:59](=O)[CH2:58][CH2:57]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl.CC(O)C>[CH2:47]([N:46]([CH2:51][CH2:52][CH2:53][CH3:54])[C:44]([C:39]1[C:40]([Cl:43])=[C:41]([CH3:42])[N:37]([C:16]2[CH:17]=[CH:18][C:19]([C:21](=[O:36])[NH:22][S:23]([C:26]3[CH:35]=[CH:34][C:33]4[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=4)[CH:27]=3)(=[O:25])=[O:24])=[CH:20][C:15]=2[C:13]([N:4]2[C@H:3]([CH2:2][NH:1][CH:59]3[CH2:60][CH2:61][N:56]([CH3:55])[CH2:57][CH2:58]3)[CH2:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[CH2:5]2)=[O:14])[N:38]=1)=[O:45])[CH2:48][CH2:49][CH3:50]

Participants

6

Reactant 3

HCID 740491-Methyl-4-piperidoneHCID 5049666Sodium triacetoxyborohydrideHCID 66561714HCID 66561714, compound

Product 1

HCID 86718894HCID 86718894, compoundYield 36.1%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-(2-((S)-3-(aminomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (Example 92, 25 mg, 0.032 mmol) in CH2Cl2 (500 μL) and i-PrOH (500 μL) was added 1-methylpiperidin-4-one (4 μL, 0.032 mmol) followed by Na(OAc)3BH (10 mg, 0.049 mmol). The resulting reaction mixture was stirred at room temperature overnight, then quenched with 2 mL of MeOH followed by 2 mL of 1N aq. NaOH solution. The mixture was poured in sat. aq. NH4Cl solution, and the aqueous layer was extracted with EtOAc (3×). The combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified using preparative HPLC to give the title compound (10 mg, 31%) as a white solid after lyophilization. 1H NMR (CD3OD, mixture of amide rotamers) δ 8.59-8.52 (m, 1H), 8.51-8.45 (m, 0.5H), 8.40-8.34 (m, 0.5H), 8.26-8.12 (m, 1H), 8.06-7.86 (m, 4H), 7.69-7.45 (m, 3H), 7.29-7.20 (m, 3.5H), 7.04-6.91 (m, 0.5H), 5.33-5.21 (m, 0.5H), 5.08-4.94 (m, 0.5H), 4.63-4.53 (m, 0.5H), 4.34-4.23 (m, 1H), 4.17-4.03 (m, 0.5H), 3.54-3.34 (m, 3.5H), 3.22-2.51 (m, 11.5H), 2.43-2.32 (m, 1H), 2.29 (s, 3H), 2.18-1.99 (m, 1H), 1.84-1.67 (m, 1.5H), 1.65-0.85 (m, 12H), 0.81-0.70 (m, 2.5H), 0.69-0.58 (m, 1H); MS(ESI+) m/z 866.4 (M+H)+.

Workup

  1. customThe resulting reaction mixture
  2. customquenched with 2 mL of MeOH
  3. additionThe mixture was poured in sat. aq. NH4Cl solution
  4. extractionthe aqueous layer was extracted with EtOAc (3×)
  5. dry with materialThe combined organic extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified

Sources & evidence

ORD record
ord-cb3a8d3f34c04b3cb44132a27fcd3db4
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

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