Acetic Acid → HCID 67981004, compound

HRID 2406247Notes

Reaction equation

HRID 2406247 reaction equation
[N:1]1([CH2:7][CH2:8][C@H:9]([N:17](C)[C:18]2[CH:23]=[CH:22][C:21]([S:24]([NH:27][C:28]3[N:32]4[CH2:33][CH2:34][NH:35][CH2:36][C:31]4=[N:30][N:29]=3)(=[O:26])=[O:25])=[CH:20][C:19]=2[S:37]([C:40]([F:43])([F:42])[F:41])(=[O:39])=[O:38])SC2C=CC=CC=2)CCO[CH2:3][CH2:2]1.[C:45]([O:49][C:50]([N:52]1[CH2:57][CH2:56][C:55](=O)[CH2:54][CH:53]1[CH3:59])=[O:51])([CH3:48])([CH3:47])[CH3:46].[C:60]([OH:63])(=O)[CH3:61].C([BH3-])#N.[Na+]>CO>[C:45]([O:49][C:50]([N:52]1[CH2:57][CH2:56][CH:55]([N:35]2[CH2:34][CH2:33][N:32]3[C:28]([NH:27][S:24]([C:21]4[CH:22]=[CH:23][C:18]([NH:17][C@@H:9]([CH2:40][S:37][C:19]5[CH:20]=[CH:21][CH:22]=[CH:23][CH:18]=5)[CH2:8][CH2:7][N:1]5[CH2:61][CH2:60][O:63][CH2:3][CH2:2]5)=[C:19]([S:37]([C:40]([F:42])([F:41])[F:43])(=[O:39])=[O:38])[CH:20]=4)(=[O:25])=[O:26])=[N:29][N:30]=[C:31]3[CH2:36]2)[CH2:54][CH:53]1[CH3:59])=[O:51])([CH3:48])([CH3:47])[CH3:46]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 12992764tert-Butyl 2-methyl-4-oxopiperidine-1-carboxylateHCID 67980785HCID 67980785, compound

Product 1

HCID 67981004HCID 67981004, compoundYield 108.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a vial containing 4-((R)-3-morpholin-4-yl-1-phenylsulfanyl-methyl-propylamino)-N-(5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazin-3-yl)-3-trifluoromethanesulfonyl-benzenesulfonamide (60 mg, 0.089 mmol) and 2-methyl-4-oxo-piperidine-1-carboxylic acid tert-butyl ester (47.3 mg, 0.222 mmol) was added methanol (3 mL) under nitrogen. The reaction mixture was stirred in an ice bath for 10 minutes and then acetic acid (6.104, 0.107 mmol) was added. After stirring in the ice bath for an additional 15 minutes, sodium cyanoborohydride (44.6 mg, 0.710 mmol) was then added, and the reaction was stirred at ambient temperature for 15 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 2-methyl-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 (42 mg, 53% yield). MS [m/z; (M+1)+]: 873.8

Workup

  1. stirringthe reaction was stirred at ambient temperature for 15 hours
  2. concentrationThe reaction mixture was concentrated
  3. filtrationfiltered
  4. custompurified via flash chromatography on silica gel (10-50% 7N NH3 in methanol in CH2Cl2)

Sources & evidence

ORD record
ord-f559b34ededf43b187a0659f50f7ae04
Source dataset
uspto-grants-2014_08
Patent number
US08809352B2

Reaction notes

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