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Sodium Bicarbonate → N-(5-{[2-(acetylamino)[1,3]thiazolo[5,4-d]pyrimidin-5-yl](methyl)amino}-2-fluorophenyl)-3-(1,1-dimethylprop-2-yn-1-yl)benzamide

HRID 1800711
Notes
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Reaction equation

HRID 1800711 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([N:9]([CH3:23])[C:10]2[N:11]=[CH:12][C:13]3[N:18]=[C:17]([NH:19][C:20](=[O:22])[CH3:21])[S:16][C:14]=3[N:15]=2)[CH:5]=[CH:6][C:7]=1[F:8].[CH3:24][C:25]([C:29]1[CH:30]=[C:31]([CH:35]=[CH:36][CH:37]=1)[C:32](O)=[O:33])([CH3:28])[C:26]#[CH:27].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(=O)([O-])O.[Na+]>N1C=CC=CC=1>[C:20]([NH:19][C:17]1[S:16][C:14]2[N:15]=[C:10]([N:9]([CH3:23])[C:4]3[CH:5]=[CH:6][C:7]([F:8])=[C:2]([NH:1][C:32](=[O:33])[C:31]4[CH:35]=[CH:36][CH:37]=[C:29]([C:25]([CH3:24])([CH3:28])[C:26]#[CH:27])[CH:30]=4)[CH:3]=3)[N:11]=[CH:12][C:13]=2[N:18]=1)(=[O:22])[CH3:21]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 862274143-(2-Methylbut-3-yn-2-yl)benzoic acidHCID 86646079N-{5-[(3-amino-4-fluorophenyl)(methyl)amino][1,3]thiazolo[5,4-d]pyrimidin-2-yl}acetamide

Product 1

HCID 59506936
N-(5-{[2-(acetylamino)[1,3]thiazolo[5,4-d]pyrimidin-5-yl](methyl)amino}-2-fluorophenyl)-3-(1,1-dimethylprop-2-yn-1-yl)benzamide
Yield 62.1%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
90 °C

Procedure

A solution of N-{5-[(3-amino-4-fluorophenyl)(methyl)amino][1,3]thiazolo[5,4-d]pyrimidin-2-yl}acetamide (100 mg, 301 μmol) produced in Example D17(iv), 3-(1,1-dimethylprop-2-yn-1-yl)benzoic acid (141 mg, 753 μmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (286 mg, 753 μmol) in pyridine (4 mL) was stirred at 90° C. for 3 hr. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate solution (15 mL), and the mixture was extracted with ethyl acetate (20 mL, 5 mL). The combined organic layer was washed with saturated brine (5 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=40/60→10/90), and the fractions containing the object product were concentrated under reduced pressure. The obtained residue was recrystallized from tetrahydrofuran and hexane to give the title compound (94 mg, 62%) as colorless crystals.

Workup

  1. extractionthe mixture was extracted with ethyl acetate (20 mL, 5 mL)
  2. washThe combined organic layer was washed with saturated brine (5 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationThe insoluble material was filtered off
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe obtained residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=40/60→10/90)
  7. additionthe fractions containing the object product
  8. concentrationwere concentrated under reduced pressure
  9. customThe obtained residue was recrystallized from tetrahydrofuran and hexane

Sources & evidence

ORD record
ord-769cff3cade944d2863012d6bf052de2
Source dataset
uspto-grants-2013_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08344135B2

Reaction notes

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