Sodium Hydroxide → 2-[(3R,4S)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl]-4-[5-(4-methylpiperazin-1-yl)pyrazin-2-yl]-1,3-thiazole-5-carboxylic acid

HRID 655736Notes

Reaction equation

HRID 655736 reaction equation
[Cl:1][C:2]1[C:6]([Cl:7])=[C:5]([CH3:8])[NH:4][C:3]=1[C:9]([NH:11][C@H:12]1[CH2:17][CH2:16][N:15]([C:18]2[S:19][C:20]([C:36]([O:38]CC)=[O:37])=[C:21]([C:23]3[CH:28]=[N:27][C:26]([N:29]4[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]4)=[CH:25][N:24]=3)[N:22]=2)[CH2:14][C@H:13]1[O:41][CH3:42])=[O:10].[OH-].[Na+]>CO>[Cl:1][C:2]1[C:6]([Cl:7])=[C:5]([CH3:8])[NH:4][C:3]=1[C:9]([NH:11][C@H:12]1[CH2:17][CH2:16][N:15]([C:18]2[S:19][C:20]([C:36]([OH:38])=[O:37])=[C:21]([C:23]3[CH:28]=[N:27][C:26]([N:29]4[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]4)=[CH:25][N:24]=3)[N:22]=2)[CH2:14][C@H:13]1[O:41][CH3:42])=[O:10]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 59402474ethyl 2-[(3R,4S)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl]-4-[5-(4-methylpiperazin-1-yl)pyrazin-2-yl]-1,3-thiazole-5-carboxylate

Product 1

HCID 462352232-[(3R,4S)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl]-4-[5-(4-methylpiperazin-1-yl)pyrazin-2-yl]-1,3-thiazole-5-carboxylic acidYield 82%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Ethyl 2-[(3R,4S)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl]-4-[5-(4-methylpiperazin-1-yl)pyrazin-2-yl]-1,3-thiazole-5-carboxylate (Example 60, 92 mg, 0.144 mM) was dissolved in methanol (15 mL). To this was added 2N sodium hydroxide (7 mL) and the reaction mixture was stirred at room temperature for 4 h. The methanol was completely evaporated and water (20 mL) was added. The aqueous layer was washed with diethyl ether (2×20 mL) and the aqueous layer was acidified to pH 6 with 2N hydrochloric acid (1.0 mL). The solid that precipitated out of solution was filtered and dried to afford 2-[(3R,4S)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl]-4-[5-(4-methylpiperazin-1-yl)pyrazin-2-yl]-1,3-thiazole-5-carboxylic acid 60 mg (82%) as an off-white solid.

Workup

  1. customThe methanol was completely evaporated
  2. additionwater (20 mL) was added
  3. washThe aqueous layer was washed with diethyl ether (2×20 mL)
  4. customThe solid that precipitated out of solution
  5. filtrationwas filtered
  6. customdried

Sources & evidence

ORD record
ord-b8983ddb051b42c0b5fb7f4eb88691c1
Source dataset
uspto-grants-2011_12
Patent number
US08071605B2

Reaction notes

Loading…