tert-Butyl 4-oxopiperidine-1-carboxylate → HCID 67980795, compound

HRID 2406245Notes

Reaction equation

HRID 2406245 reaction equation
[N:1]1([CH2:7][CH2:8][C@@H:9]([N:16](CS)[C:17]2[CH:22]=[CH:21][C:20]([S:23]([NH:26][C:27]3[N:31]4[CH2:32][CH2:33][NH:34][CH2:35][C:30]4=[N:29][N:28]=3)(=[O:25])=[O:24])=[CH:19][C:18]=2[S:36]([C:39]([F:42])([F:41])[F:40])(=[O:38])=[O:37])C2C=CC=CC=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[C:45]([O:49][C:50]([N:52]1[CH2:57][CH2:56][C:55](=O)[CH2:54][CH2:53]1)=[O:51])([CH3:48])([CH3:47])[CH3:46].C([BH3-])#N.[Na+]>C(O)(=O)C.CO>[C:45]([O:49][C:50]([N:52]1[CH2:57][CH2:56][CH:55]([N:34]2[CH2:33][CH2:32][N:31]3[C:27]([NH:26][S:23]([C:20]4[CH:21]=[CH:22][C:17]([NH:16][C@@H:9]([CH2:39][S:36][C:18]5[CH:19]=[CH:20][CH:21]=[CH:22][CH:17]=5)[CH2:8][CH2:7][N:1]5[CH2:6][CH2:5][O:4][CH2:3][CH2:2]5)=[C:18]([S:36]([C:39]([F:40])([F:41])[F:42])(=[O:38])=[O:37])[CH:19]=4)(=[O:25])=[O:24])=[N:28][N:29]=[C:30]3[CH2:35]2)[CH2:54][CH2:53]1)=[O:51])([CH3:48])([CH3:47])[CH3:46]

Participants

6

Reactant 3

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5003444Sodium cyanoborohydrideHCID 88540108HCID 88540108, compound

Product 1

HCID 67980795HCID 67980795, compoundYield 204.5%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 887MethanolSolvent

Procedure

To a vial containing 4-((R)-3-morpholin-4-yl-1-phenyl-sulfanylmethyl-propylamino)-N-(5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazin-3-yl)-3-trifluoromethanesulfonyl-benzenesulfonamide (50 mg, 0.074 mmol) and 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (14.74 mg, 0.074 mmol) was added methanol (2 mL) under nitrogen. The reaction mixture was stirred in an ice bath for 10 minutes, and then acetic acid (0.424 μL, 7.40 μmol) was added. The reaction mixture was stirred for another 30 minutes. Sodium cyanoborohydride (41.85 mg, 0.666 mmol) was then added, and the reaction was stirred at ambient temperature for 72 hours. The reaction mixture was concentrated, filtered and purified via flash chromatography on silica gel (10-50% 7N NH3 in methanol in CH2Cl2) to afford 4-{3-[4-((R)-3-Morpholin-4-yl-1-phenylsulfanylmethyl-propylamino)-3-trifluoromethanesulfonyl-benzenesulfonylamino]-5,6-dihydro-8H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl}-piperidine-1-carboxylic acid tert-butyl ester (65 mg, 100% yield). MS [m/z; (M+1)+]: 859.7

Workup

  1. stirringThe reaction mixture was stirred for another 30 minutes
  2. stirringthe reaction was stirred at ambient temperature for 72 hours
  3. concentrationThe reaction mixture was concentrated
  4. filtrationfiltered
  5. custompurified via flash chromatography on silica gel (10-50% 7N NH3 in methanol in CH2Cl2)

Sources & evidence

ORD record
ord-8769df45335c403e89e81197b567902b
Source dataset
uspto-grants-2014_08
Patent number
US08809352B2

Reaction notes

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