Hydrochloric Acid → Methyl 2-chloro-4-[4-(piperidin-1-yl)pyrimidin-2-yl]-1,3-thiazole-5-carboxylate

HRID 655783Notes

Reaction equation

HRID 655783 reaction equation
N[C:2]1[S:3][C:4]([C:19]([O:21][CH3:22])=[O:20])=[C:5]([C:7]2[N:12]=[C:11]([N:13]3[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]3)[CH:10]=[CH:9][N:8]=2)[N:6]=1.N([O-])=O.[Na+].C(=O)(O)[O-].[Na+].[ClH:32]>O>[Cl:32][C:2]1[S:3][C:4]([C:19]([O:21][CH3:22])=[O:20])=[C:5]([C:7]2[N:12]=[C:11]([N:13]3[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]3)[CH:10]=[CH:9][N:8]=2)[N:6]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 23668193Sodium NitriteHCID 59402564Methyl 2-amino-4-[4-(piperidin-1-yl)pyrimidin-2-yl]-1,3-thiazole-5-carboxylate2×

Product 1

HCID 59402524Methyl 2-chloro-4-[4-(piperidin-1-yl)pyrimidin-2-yl]-1,3-thiazole-5-carboxylateYield 54%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a stirred solution of methyl 2-amino-4-[4-(piperidin-1-yl)pyrimidin-2-yl]-1,3-thiazole-5-carboxylate (Intermediate 62, 0.070 g, 0.219 mmol) in concentrated HCl (1 mL), sodium nitrite (0.045 g, 0.658 mmol) in water (1 mL) was added drop wise at 0° C. The reaction mixture was stirred at room temperature for 30 min. The reaction mixture was cooled to 5-10° C. and basified with saturated sodium bicarbonate solution (20 mL). The aqueous layer was extracted with ethyl acetate (2×30 mL). The combined organic layer was washed with brine solution, dried and concentrated under reduced pressure to obtain methyl 2-chloro-4-[4-(piperidin-1-yl)pyrimidin-2-yl]-1,3-thiazole-5-carboxylate 0.040 g (54%).

Workup

  1. extractionThe aqueous layer was extracted with ethyl acetate (2×30 mL)
  2. washThe combined organic layer was washed with brine solution
  3. customdried
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-bd6eb21a19dd4eb98daeceaae575a2ac
Source dataset
uspto-grants-2011_12
Patent number
US08071605B2

Reaction notes

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