Sulfuric Acid → 2-chloro-3-(1-cyano-1-methylethoxy)-N-{5-[{2-[(cyclopropylcarbonyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}(methyl)amino]-2-fluorophenyl}benzamide sulfate

HRID 1800643Notes

Reaction equation

HRID 1800643 reaction equation
[Cl:1][C:2]1[C:34]([O:35][C:36]([C:39]#[N:40])([CH3:38])[CH3:37])=[CH:33][CH:32]=[CH:31][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[C:11]([N:13]([C:15]2[N:20]=[C:19]3[S:21][C:22]([NH:24][C:25]([CH:27]4[CH2:29][CH2:28]4)=[O:26])=[N:23][C:18]3=[CH:17][CH:16]=2)[CH3:14])[CH:10]=[CH:9][C:8]=1[F:30])=[O:5].[S:41](=[O:45])(=[O:44])([OH:43])[OH:42]>C(OCC)(=O)C.CCCCCCC>[S:41]([OH:45])([OH:44])(=[O:43])=[O:42].[Cl:1][C:2]1[C:34]([O:35][C:36]([C:39]#[N:40])([CH3:38])[CH3:37])=[CH:33][CH:32]=[CH:31][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[C:11]([N:13]([C:15]2[N:20]=[C:19]3[S:21][C:22]([NH:24][C:25]([CH:27]4[CH2:29][CH2:28]4)=[O:26])=[N:23][C:18]3=[CH:17][CH:16]=2)[CH3:14])[CH:10]=[CH:9][C:8]=1[F:30])=[O:5]

Participants

5

Reactant 2

HCID 1118Sulfuric AcidHCID 252063462-Chloro-3-[(2-Cyanopropan-2-Yl)oxy]-N-{5-[{2-[(Cyclopropylcarbonyl)amino][1,3]thiazolo[5,4-B]pyridin-5-Yl}(Methyl)amino]-2-Fluorophenyl}benzamide

Product 1

HCID 714522512-chloro-3-(1-cyano-1-methylethoxy)-N-{5-[{2-[(cyclopropylcarbonyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}(methyl)amino]-2-fluorophenyl}benzamide sulfateYield 80%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolvent2×HCID 8900HeptaneSolvent

Conditions

Temperature
50 °C

Procedure

2-Chloro-3-(1-cyano-1-methylethoxy)-N-{5-[{2-[(cyclopropylcarbonyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}(methyl)amino]-2-fluorophenyl}benzamide (150 mg, 0.259 mmol) produced in Example C122(xi) was dissolved in ethyl acetate (6 mL), and the solution was added dropwise to a suspension of sulfuric acid (51 mg, 0.52 mmol) in heptane at room temperature. Ethyl acetate (12 mL) was added, and the mixture was stirred at 50° C. for 15 min. The solution was concentrated under reduced pressure, tetrahydrofuran and heptane were added to the obtained residue at 50° C., and the mixture was cooled to room temperature. The crystallized crystals were collected by filtration, and dried to give the title compound (140 mg, 80%) as colorless crystals.

Workup

  1. concentrationThe solution was concentrated under reduced pressure, tetrahydrofuran and heptane
  2. additionwere added to the obtained residue at 50° C.
  3. temperaturethe mixture was cooled to room temperature
  4. filtrationThe crystallized crystals were collected by filtration
  5. customdried

Sources & evidence

ORD record
ord-ee6a281970d94ba0916d51e1a82045ec
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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