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Methanol → 3-(1,3-Benzoxazol-2-yl)-5-[2-(4-methylpiperazin-1-yl)thiazol-5-yl]pyridin-2-amine

HRID 908392
Notes
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Reaction equation

HRID 908392 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[C:11]([NH2:25])=[N:12][CH:13]=[C:14](B2OC(C)(C)C(C)(C)O2)[CH:15]=1.Br[C:27]1[S:31][C:30]([N:32]2[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]2)=[N:29][CH:28]=1.[F-].[Cs+].CO>C(#N)C.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[C:11]([NH2:25])=[N:12][CH:13]=[C:14]([C:27]2[S:31][C:30]([N:32]3[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]3)=[N:29][CH:28]=2)[CH:15]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 887MethanolHCID 25953Cesium fluorideHCID 457875521-(5-Bromo-1,3-thiazol-2-yl)-4-methylpiperazineHCID 673889123-(1,3-Benzoxazol-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine

Product 1

HCID 673884383-(1,3-Benzoxazol-2-yl)-5-[2-(4-methylpiperazin-1-yl)thiazol-5-yl]pyridin-2-amineYield 45.8%

Reagents, catalysts & solvents 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

Compound [5] was prepared as follows. 3-(1,3-benzoxazol-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (150 mg), 1-(5-bromothiazol-2-yl)-4-methyl-piperazine (117 mg), bis(triphenylphosphine) palladium (II) chloride (15.61 mg) and caesium fluoride (169 mg) were weighed out in a microwave vial and sealed. Methanol (1.5 ml) was added and argon was bubbled in the resulting suspension for 10 minutes. The resulting mixture was heated in the 300 W microwave at 120° C. for 20 minutes. The crude product was purified by flash chromatography on silica gel eluting with 0 to 3% methanol in dichloromethane then 3% to 5% methanolic ammonia 7N in dichloromethane. The solvent was evaporated to dryness to afford the product, which was stirred at room temperature for 1 h in acetonitrile (3 ml), collected by filtration, washed with acetonitrile and dried under vacuum at 40° C., to give 3-(1,3-benzoxazol-2-yl)-5-[2-(4-methylpiperazin-1-yl)thiazol-5-yl]pyridin-2-amine (80 mg). NMR Spectrum: (CDCl3) 2.39 (s, 3H), 2.54-2.65 (m, 4H), 3.56-3.65 (m, 4H), 6.96 (m, 2H), 7.35 (s, 1H), 7.36-7.40 (m, 2H), 7.61 (dd, 1H), 7.74 (dd, 1H), 8.31-8.35 (m, 2H); Mass spectrum: M+H+ 393. There was no deprotection step.

Workup

  1. customsealed
  2. customargon was bubbled in the resulting suspension for 10 minutes
  3. customThe crude product was purified by flash chromatography on silica gel eluting with 0 to 3% methanol in dichloromethane
  4. customThe solvent was evaporated to dryness
  5. customto afford the product, which
  6. filtrationcollected by filtration
  7. washwashed with acetonitrile
  8. customdried under vacuum at 40° C.

Sources & evidence

ORD record
ord-0c53394533b64608b0e638a090808824
Source dataset
uspto-grants-2011_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08017611B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes