Formaldehyde → HCID 68983737, compound

HRID 1467877Notes

Reaction equation

HRID 1467877 reaction equation
[CH2:1]([N:5]([CH:19]1[CH2:24][CH2:23][N:22]([C:25](=[O:33])[CH:26]([NH:31][CH3:32])[CH2:27][CH:28]([CH3:30])[CH3:29])[CH2:21][CH2:20]1)[S:6]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=1)(=[O:8])=[O:7])[CH2:2][CH2:3][CH3:4].[CH3:34]O.C=O>C(O)(=O)C>[CH2:1]([N:5]([CH:19]1[CH2:24][CH2:23][N:22]([C:25](=[O:33])[CH:26]([NH:31][CH3:32])[CH2:27][CH:28]([CH3:30])[CH3:29])[CH2:21][CH2:20]1)[S:6]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:16])[F:17])[CH:10]=1)(=[O:8])=[O:7])[CH2:2][CH2:3][CH3:4].[CH:1]1([N:5]([CH:19]2[CH2:20][CH2:21][N:22]([C:25](=[O:33])[CH:26]([N:31]([CH3:32])[CH3:34])[CH2:27][CH:28]([CH3:30])[CH3:29])[CH2:23][CH2:24]2)[S:6]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:16])[F:17])[CH:10]=2)(=[O:8])=[O:7])[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 887MethanolHCID 68983609HCID 68983609, compound

Product 2

HCID 68983609HCID 68983609, compoundHCID 68983737HCID 68983737, compoundYield 10%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of (2S) N-cyclopropyl-N-[1-(4-methyl-2-methylamino-pentanoyl)piperidin-4-yl]-3-trifluoromethylbenzenesulfonamide (see Example 10, 323 mg, 0.7 mmol), methanol (4 mL), paraformaldehyde (50 mg, 1.0 mmol), NaBH3(CN) (132 mg, 2 mmol), and acetic acid (0.01 mL) was shaken at room temperature for 20 hours. The solvents were removed under vacuum. The residue was dissolved in dichloromethane (15 mL), and treated with aqueous saturated K2CO3 (5 mL). The organic layer was separated, washed with brine, concentrated under vacuum, and purified by column (silica gel, EtOAc/hexane 3/7) to give the title compound (2S) N-cyclopropyl-N-[1-(2-dimethylamino-4-methylpentanoyl)piperidin-4-yl]-3-trifluoromethyl-benzenesulfonamide as white solid (30 mg, yield 10%). 1H NMR (CDCl3): δ 8.14 (s, 1H), 8.08 (d, 1H, J=7.9 Hz), 7.87 (d, 1H, J=7.7 Hz), 7.7 (dd, 1H, J=7.7 & 8.1 Hz), 4.7-4.76 (m, 1H), 4.18-4.24 (m, 1H), 4.06-4.12 (m, 1H), 3.34-3.4 (m, 1H), 2.94-3.06 (m, 1H), 2.44-2.54 (m, 1H), 2.26 (br, 6H), 1.35-1.98 (m, 8H), 0.94-1.02 (m, 2H), 0.86-0.95 (m, 6H), 0.74-0.78 (m, 2H). LC: 100%. MS (e/z), 490 (m+1).

Workup

  1. customThe solvents were removed under vacuum
  2. dissolutionThe residue was dissolved in dichloromethane (15 mL)
  3. additiontreated with aqueous saturated K2CO3 (5 mL)
  4. customThe organic layer was separated
  5. washwashed with brine
  6. concentrationconcentrated under vacuum
  7. custompurified by column (silica gel, EtOAc/hexane 3/7)

Sources & evidence

ORD record
ord-39fd9d7752a0403ca5e6621c9c203bff
Source dataset
uspto-grants-2015_04
Patent number
US09000174B2

Reaction notes

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