Water → N-acetyl-2-chloro-3-(1-cyanocyclopropyl)-N-[5-({2-[(cyclopropylcarbonyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)-2-fluorophenyl]benzamide

HRID 1800661Notes

Reaction equation

HRID 1800661 reaction equation
[Cl:1][C:2]1[C:33]([C:34]2([C:37]#[N:38])[CH2:36][CH2:35]2)=[CH:32][CH:31]=[CH:30][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[C:11]([O:13][C:14]2[N:19]=[C:18]3[S:20][C:21]([NH:23][C:24]([CH:26]4[CH2:28][CH2:27]4)=[O:25])=[N:22][C:17]3=[CH:16][CH:15]=2)[CH:10]=[CH:9][C:8]=1[F:29])=[O:5].[C:39](OC(=O)C)(=[O:41])[CH3:40].O>N1C=CC=CC=1.CN(C)C1C=CN=CC=1>[C:39]([N:6]([C:7]1[CH:12]=[C:11]([O:13][C:14]2[N:19]=[C:18]3[S:20][C:21]([NH:23][C:24]([CH:26]4[CH2:28][CH2:27]4)=[O:25])=[N:22][C:17]3=[CH:16][CH:15]=2)[CH:10]=[CH:9][C:8]=1[F:29])[C:4](=[O:5])[C:3]1[CH:30]=[CH:31][CH:32]=[C:33]([C:34]2([C:37]#[N:38])[CH2:36][CH2:35]2)[C:2]=1[Cl:1])(=[O:41])[CH3:40]

Participants

6

Reactant 3

HCID 962WaterHCID 7918Acetic AnhydrideHCID 252061852-Chloro-3-(1-Cyanocyclopropyl)-N-[5-({2-[(Cyclopropylcarbonyl)amino][1,3]thiazolo[5,4-B]pyridin-5-Yl}oxy)-2-Fluorophenyl]benzamide

Product 1

HCID 45255352N-acetyl-2-chloro-3-(1-cyanocyclopropyl)-N-[5-({2-[(cyclopropylcarbonyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)-2-fluorophenyl]benzamideYield 35.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Procedure

To a solution of 2-chloro-3-(1-cyanocyclopropyl)-N-[5-({2-[(cyclopropylcarbonyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)-2-fluorophenyl]benzamide (180 mg, 0.328 mmol) in pyridine (2 mL) were added N,N-dimethylpyridine-4-amine (18.0 mg, 0.147 mmol) and acetic anhydride (138 μL, 1.46 mmol), and the mixture was stirred at room temperature for 30 min. To the reaction mixture was added water (5 mL), and the mixture was extracted with ethyl acetate (5mL×4). The organic layers were combined, washed successively with water (5 mL) and saturated brine (5 mL), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=95/5→20/80) and, preparative liquid chromatography (0.1% trifluoroacetic acid-containing acetonitrile/0.1% trifluoroacetic acid-containing water=45/55→60/40). The obtained residue was triturated with diisopropyl ether/acetone to give the title compound (68.5 mg, 35%) as a white powder.

Workup

  1. extractionthe mixture was extracted with ethyl acetate (5mL×4)
  2. washwashed successively with water (5 mL) and saturated brine (5 mL)
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=95/5→20/80) and, preparative liquid chromatography (0.1% trifluoroacetic acid-containing acetonitrile/0.1% trifluoroacetic acid-containing water=45/55→60/40)
  6. customThe obtained residue was triturated with diisopropyl ether/acetone

Sources & evidence

ORD record
ord-080a701cd25545ee942f677d2a2d2c86
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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