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

HRID 1800662Notes

Reaction equation

HRID 1800662 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].[CH:39]1([C:42](Cl)=[O:43])[CH2:41][CH2:40]1>N1C=CC=CC=1.CN(C)C1C=CN=CC=1>[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]([N:6]([C:42]([CH:39]1[CH2:41][CH2:40]1)=[O:43])[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]

Participants

5

Reactant 2

HCID 77637Cyclopropanecarbonyl chlorideHCID 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 452553512-chloro-3-(1-cyanocyclopropyl)-N-(cyclopropylcarbonyl)-N-[5-({2-[(cyclopropylcarbonyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)-2-fluorophenyl]benzamideYield 63%

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 (3.5 g, 6.39 mmol) produced in Example C127(x) in pyridine (35 mL) were added N,N-dimethylpyridine-4-amine (3.87 g, 31.7 mmol) and cyclopropanecarbonyl chloride (3.0 mL, 33.1 mmol) at 10° C., and the mixture was stirred at room temperature for 1.5 hr. The reaction mixture was poured into ice water (70 mL), and the mixture was extracted with ethyl acetate (80 mL×3). The organic layers were combined, washed successively with water (50 mL) and saturated brine (30 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). The obtained residue was recrystallized from ethyl acetate to give the title compound (2.47 g, 63%) as white crystals.

Workup

  1. extractionthe mixture was extracted with ethyl acetate (80 mL×3)
  2. washwashed successively with water (50 mL) and saturated brine (30 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)
  6. customThe obtained residue was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-fd9628f4ab434843a0f5ba418692f379
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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