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

HRID 655743Notes

Reaction equation

HRID 655743 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:35]([O:37]C)=[O:36])=[C:21]([C:23]3[N:28]=[C:27]([N:29]4[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]4)[CH:26]=[CH:25][N:24]=3)[N:22]=2)[CH2:14][C@@H:13]1[O:39][CH3:40])=[O:10].[OH-].[Li+]>O1CCCC1.O>[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:35]([OH:37])=[O:36])=[C:21]([C:23]3[N:28]=[C:27]([N:29]4[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]4)[CH:26]=[CH:25][N:24]=3)[N:22]=2)[CH2:14][C@@H:13]1[O:39][CH3:40])=[O:10]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 59402451methyl 2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl]-4-[4-(piperidin-1-yl)pyrimidin-2-yl]-1,3-thiazole-5-carboxylate

Product 1

HCID 594025002-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl]-4-[4-(piperidin-1-yl)pyrimidin-2-yl]-1,3-thiazole-5-carboxylic acidYield 79%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of methyl 2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl]-4-[4-(piperidin-1-yl)pyrimidin-2-yl]-1,3-thiazole-5-carboxylate (Example 184, 35 mg. 0.06 mmol) in tetrahydrofuran (5 mL) was added a solution of lithium hydroxide (9.6 mg, 0.23 mmol) in water (1 mL). The reaction mixture was stirred at room temperature for 18 h. The reaction mixture was concentrated to dryness. The resulting residue was diluted with water (2 mL) and the aqueous layer was extracted with diethyl ether (2×10 mL). The aqueous layer was acidified to pH 4-5 with 2N HCl solution, solid obtained was filtered and dried to yield 2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl]-4-[4-(piperidin-1-yl)pyrimidin-2-yl]-1,3-thiazole-5-carboxylic acid 27 mg (79%).

Workup

  1. concentrationThe reaction mixture was concentrated to dryness
  2. additionThe resulting residue was diluted with water (2 mL)
  3. extractionthe aqueous layer was extracted with diethyl ether (2×10 mL)
  4. customobtained
  5. filtrationwas filtered
  6. customdried

Sources & evidence

ORD record
ord-da14a824d31c43ca9816b1670e4accd0
Source dataset
uspto-grants-2011_12
Patent number
US08071605B2

Reaction notes

Loading…