Ethyl Acetate → 2-chloro-N-[2-chloro-5-({2-[(cyclopropylcarbonyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)phenyl]-3-(1-cyano-1-methylethoxy)benzamide

HRID 1800633Notes

Reaction equation

HRID 1800633 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][C:23]=1[Cl:24])[O:5][C:6]1[N:11]=[C:10]2[S:12][C:13]([NH:15][C:16]([CH:18]3[CH2:20][CH2:19]3)=[O:17])=[N:14][C:9]2=[CH:8][CH:7]=1.[Cl:25][C:26]1[C:34]([O:35][C:36]([C:39]#[N:40])([CH3:38])[CH3:37])=[CH:33][CH:32]=[CH:31][C:27]=1[C:28](O)=[O:29].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(OCC)(=O)C>N1C=CC=CC=1.O>[Cl:25][C:26]1[C:34]([O:35][C:36]([C:39]#[N:40])([CH3:37])[CH3:38])=[CH:33][CH:32]=[CH:31][C:27]=1[C:28]([NH:1][C:2]1[CH:3]=[C:4]([O:5][C:6]2[N:11]=[C:10]3[S:12][C:13]([NH:15][C:16]([CH:18]4[CH2:20][CH2:19]4)=[O:17])=[N:14][C:9]3=[CH:8][CH:7]=2)[CH:21]=[CH:22][C:23]=1[Cl:24])=[O:29]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57384284N-[5-(3-amino-4-chlorophenoxy) [1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamideHCID 684177462-Chloro-3-(1-cyano-1-methylethoxy)benzoic acid

Product 1

HCID 595070252-chloro-N-[2-chloro-5-({2-[(cyclopropylcarbonyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)phenyl]-3-(1-cyano-1-methylethoxy)benzamideYield 24.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1049PyridineSolvent

Conditions

Temperature
60 °C

Procedure

N-[5-(3-Amino-4-chlorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamide (200 mg, 0.554 mmol) produced in Example C118(ii), 2-chloro-3-(1-cyano-1-methylethoxy)benzoic acid (199 mg, 0.830 mmol) produced in Example C70(i) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (422 mg, 1.11 mmol) were suspended in pyridine (2 mL), and the suspension was stirred at 60° C. for 16 hr. After cooling to room temperature, ethyl acetate (100 mL) and water (80 mL) were added, and the mixture was partitioned. The organic layer was washed with saturated brine (50 mL), dried over anhydrous magnesium sulfate, and dried under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=40/60→100/0) and basic silica gel column chromatography (ethyl acetate/methanol=100/0→90/10), and triturated with diisopropyl ether to give the title compound (78 mg, 24%) as white crystals.

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe mixture was partitioned
  3. washThe organic layer was washed with saturated brine (50 mL)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customdried under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane=40/60→100/0) and basic silica gel column chromatography (ethyl acetate/methanol=100/0→90/10)
  7. customtriturated with diisopropyl ether

Sources & evidence

ORD record
ord-cb5d80c9166647f09256df448af876d2
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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