Water → Methyl N-[6-({[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}sulfanyl)-3,5-dicyano-4-piperidin-1-ylpyridin-2-yl]-N-methylglycinate

HRID 1913501Notes

Reaction equation

HRID 1913501 reaction equation
Cl[C:2]1[C:7]([C:8]#[N:9])=[C:6]([N:10]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)[C:5]([C:16]#[N:17])=[C:4]([S:18][CH2:19][C:20]2[N:21]=[C:22]([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=3)[S:23][CH:24]=2)[N:3]=1.Cl.[NH:33]([CH2:35][C:36]([O:38][CH3:39])=[O:37])[CH3:34].C(N(CC)CC)C.O>C1COCC1>[Cl:31][C:28]1[CH:27]=[CH:26][C:25]([C:22]2[S:23][CH:24]=[C:20]([CH2:19][S:18][C:4]3[N:3]=[C:2]([N:33]([CH3:34])[CH2:35][C:36]([O:38][CH3:39])=[O:37])[C:7]([C:8]#[N:9])=[C:6]([N:10]4[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]4)[C:5]=3[C:16]#[N:17])[N:21]=2)=[CH:30][CH:29]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 83544Glycine, N-methyl-, methyl ester, hydrochloride (1:1)HCID 866400092-Chloro-6-({[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}sulfanyl)-4-piperidin-1-ylpyridine-3,5-dicarbonitrile

Product 1

HCID 66671863Methyl N-[6-({[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}sulfanyl)-3,5-dicyano-4-piperidin-1-ylpyridin-2-yl]-N-methylglycinate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

100 mg (0.21 mmol) of the compound from Example 46A were dissolved in 2 ml of dry THF. 57 mg (0.41 mmol) of methyl sarcosinate hydrochloride and 86 μl (0.62 mmol) of triethylamine were then added in succession. The reaction mixture was stirred at RT for 10 h. 1 ml of water was added, and the mixture was extracted three times with in each case 5 ml of ethyl acetate. The combined organic phases were washed once with 3 ml of saturated aqueous sodium chloride solution and dried over magnesium sulfate. After removal of the solvent on a rotary evaporator, the residue was purified by preparative HPLC (column: YMC GEL ODS-AQ S-5/15 μm; mobile phase gradient: acetonitrile/water 10:90→95:5).

Workup

  1. extractionthe mixture was extracted three times with in each case 5 ml of ethyl acetate
  2. washThe combined organic phases were washed once with 3 ml of saturated aqueous sodium chloride solution
  3. dry with materialdried over magnesium sulfate
  4. customAfter removal of the solvent
  5. customon a rotary evaporator
  6. customthe residue was purified by preparative HPLC (column: YMC GEL ODS-AQ S-5/15 μm; mobile phase gradient: acetonitrile/water 10:90→95:5)

Sources & evidence

ORD record
ord-a25999c05d05450798ae0f5e21579f08
Source dataset
uspto-grants-2013_12
Patent number
US08609686B2

Reaction notes

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