Triethylamine → 4-(1-{[3-Chloro-6-(trifluoromethyl)-1-benzothiophen-2-yl]carbonyl}azetidin-3-yl)-1-pyrimidin-2-ylpiperazin-2-one

HRID 473597Notes

Reaction equation

HRID 473597 reaction equation
C([O:5][C:6]([N:8]1[CH2:11][CH:10]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[N:23]=[CH:22][CH:21]=[CH:20][N:19]=3)[C:14](=[O:24])[CH2:13]2)[CH2:9]1)=O)(C)(C)C.CCN(CC)CC.[Cl:32][C:33]1[C:34]2[CH:44]=[CH:43][C:42]([C:45]([F:48])([F:47])[F:46])=[CH:41][C:35]=2[S:36][C:37]=1C(Cl)=O.ClC1C2C=CC(C(F)(F)F)=CC=2SC=1C(O)=O>C(Cl)Cl.C(O)(C(F)(F)F)=O>[Cl:32][C:33]1[C:34]2[CH:44]=[CH:43][C:42]([C:45]([F:47])([F:46])[F:48])=[CH:41][C:35]=2[S:36][C:37]=1[C:6]([N:8]1[CH2:9][CH:10]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[N:19]=[CH:20][CH:21]=[CH:22][N:23]=3)[C:14](=[O:24])[CH2:13]2)[CH2:11]1)=[O:5]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 125946403-Chloro-6-trifluoromethyl-benzo[b]thiophene-2-carbonyl chlorideHCID 162283873-Chloro-6-(trifluoromethyl)-1-benzothiophene-2-carboxylic acidHCID 668362493-(3-Oxo-4-pyrimidin-2-yl-piperazin-1-yl)-azetidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 668235484-(1-{[3-Chloro-6-(trifluoromethyl)-1-benzothiophen-2-yl]carbonyl}azetidin-3-yl)-1-pyrimidin-2-ylpiperazin-2-one

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of intermediate 3c (prepared by procedures described in Example 4) in CH2Cl2 (2 mL) and TFA (0.5 mL) was stirred at room temperature for 1h. The solution was concentrated, and the residue was dissolved in CH2Cl2 (2.5 mL). To the resulting solution at 0° C. was added Et3N (0.11 mL, 0.79 mmol), followed by a solution of 3-chloro-6-trifluoromethyl-benzo[b]thiophene-2-carbonyl chloride 5a (prepared from 3-chloro-6-trifluoromethyl-benzo[b]thiophene-2-carboxylic acid following the procedures described in Example 1, Step A) (0.14 mmol) in CH2Cl2 (1.5 mL). The reaction was slowly warmed up to room temperature in 2 h, and was then quenched with aq. NaHCO3. The mixture was extracted with CH2Cl2. The organic solution was dried over Na2SO4 and concentrated. Purification by column chromatography (silica gel, 3% MeOH/CH2Cl2) gave Cpd 8 as yellow solid (28 mg). MS 496 (M+H+).

Workup

  1. concentrationThe solution was concentrated
  2. dissolutionthe residue was dissolved in CH2Cl2 (2.5 mL)
  3. customwas then quenched with aq. NaHCO3
  4. extractionThe mixture was extracted with CH2Cl2
  5. dry with materialThe organic solution was dried over Na2SO4
  6. concentrationconcentrated
  7. customPurification by column chromatography (silica gel, 3% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-d66f45469787432ca6cf6918ffc9f31d
Source dataset
uspto-grants-2014_01
Patent number
US08637498B2

Reaction notes

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