Potassium Carbonate → 3-Chloro-N-{6-methyl-2-(1H-pyrazol-4-yl)-3-[5-(1-pyrrolidinyl)-3-pyridinyl]thieno[2,3-b]pyridin-4-yl}benzenesulfonamide

HRID 573681Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 573681
Br[C:2]1[C:10]2[C:5](=[N:6][C:7]([CH3:22])=[CH:8][C:9]=2[NH:11][S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[CH:16]=2)(=[O:14])=[O:13])[S:4][C:3]=1[C:23]1[CH:24]=[N:25][N:26](C(OC(C)(C)C)=O)[CH:27]=1.[N:35]1([C:40]2[CH:41]=[N:42][CH:43]=[C:44](B3OC(C)(C)C(C)(C)O3)[CH:45]=2)[CH2:39][CH2:38][CH2:37][CH2:36]1.C(=O)([O-])[O-].[K+].[K+].O1CCOCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O.CN(C=O)C>[Cl:21][C:17]1[CH:16]=[C:15]([S:12]([NH:11][C:9]2[CH:8]=[C:7]([CH3:22])[N:6]=[C:5]3[S:4][C:3]([C:23]4[CH:27]=[N:26][NH:25][CH:24]=4)=[C:2]([C:44]4[CH:43]=[N:42][CH:41]=[C:40]([N:35]5[CH2:39][CH2:38][CH2:37][CH2:36]5)[CH:45]=4)[C:10]=23)(=[O:14])=[O:13])[CH:20]=[CH:19][CH:18]=1

Komponenten

9

Edukt 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 584122943-(Pyrrolidin-1-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 683240291,1-Dimethylethyl 4-(3-bromo-4-{[(3-chlorophenyl)sulfonyl]amino}-6-methylthieno[2,3-b]pyridin-2-yl)-1H-pyrazole-1-carboxylate

Produkt 1

HCID 683240533-Chloro-N-{6-methyl-2-(1H-pyrazol-4-yl)-3-[5-(1-pyrrolidinyl)-3-pyridinyl]thieno[2,3-b]pyridin-4-yl}benzenesulfonamideAusbeute 64,7 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 178418476HCID 178418476, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A mixture of 1,1-dimethylethyl 4-(3-bromo-4-{[(3-chlorophenyl)sulfonyl]amino}-6-methylthieno[2,3-b]pyridin-2-yl)-1H-pyrazole-1-carboxylate (Description 75) (100 mg, 0.171 mmol), 3-(1-Pyrrolidinyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (Description 79) (181 mg, 0.66 mmol), potassium carbonate (71.0 mg, 0.514 mmol), tetrakis(triphenylphosphine)palladium(0) (19.79 mg, 0.017 mmol) and bis(triphenylphosphine)palladium(II) chloride (12.02 mg, 0.017 mmol) were weighed into a microwave vial. 1,4-Dioxane (2 mL), DMF (1 mL) and water (0.5 mL) were added and the mixture heated in a microwave at 120° C. for 15 min. At this point, all three mixtures were combined and concentrated. The residue was passed through an SCX cartridge, eluting with MeOH (75 mL) and then 2M NH3 in MeOH (150 mL). The basic methanolic solution was concentrated and purified by normal phase chromatography, eluting with 0-10% MeOH in DCM and then further purified by MDAP (acidic conditions), to give the title compound (61 mg). LCMS (A) m/z: 551 [M+1]+, Rt 0.79 min (acidic).

Aufarbeitung

  1. concentrationconcentrated
  2. washeluting with MeOH (75 mL)
  3. concentrationThe basic methanolic solution was concentrated
  4. custompurified by normal phase chromatography
  5. washeluting with 0-10% MeOH in DCM
  6. customfurther purified by MDAP (acidic conditions)

Quellen und Nachweise

ORD-Eintrag
ord-abb9311e331142e496ac66d2c696e78f
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09029545B2

Notizen zur Reaktion

Wird geladen…