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

HRID 573679ノート

反応式

HRID 573679 の反応式
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.CC1(C)C(C)(C)OB([C:43]2[CH:44]=[C:45]([N:49]3[CH2:53][CH2:52][CH2:51][CH2:50]3)[CH:46]=[CH:47][CH:48]=2)O1.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:47]4[CH:48]=[CH:43][CH:44]=[C:45]([N:49]5[CH2:50][CH2:51][CH2:52][CH2:53]5)[CH:46]=4)[C:10]=23)(=[O:14])=[O:13])[CH:20]=[CH:19][CH:18]=1

参加物

9

反応物 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 185257431-[3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyrrolidineHCID 683240291,1-Dimethylethyl 4-(3-bromo-4-{[(3-chlorophenyl)sulfonyl]amino}-6-methylthieno[2,3-b]pyridin-2-yl)-1H-pyrazole-1-carboxylate

生成物 1

HCID 683237583-Chloro-N-{6-methyl-2-(1H-pyrazol-4-yl)-3-[3-(1-pyrrolidinyl)phenyl]thieno[2,3-b]pyridin-4-yl}benzenesulfonamide収率 100.7%

試薬・触媒・溶媒 4

HCID 178418397HCID 178418397、化合物触媒HCID 178418476HCID 178418476、化合物触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
120 °C

実験手順

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) (200 mg, 0.343 mmol), 1-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyrrolidine (140 mg, 0.514 mmol), potassium carbonate (142 mg, 1.03 mmol), tetrakis(triphenylphosphine)palladium(0) (39.6 mg, 0.034 mmol) and bis(triphenylphosphine)palladium(II) chloride (24.04 mg, 0.034 mmol) were weighed into a microwave vial. 1,4-Dioxane (3.0 mL), DMF (1.5 mL) and water (0.75 mL) were added and the mixture heated in a microwave at 120° C. for 30 min. At this point, the four reaction mixtures were combined and concentrated. The residue was passed through an SCX cartridge, eluting with MeOH (250 mL) and then 2M NH3 in MeOH (300 mL). The basic methanolic solution was concentrated and purified by normal phase chromatography eluting with 0-10% 2M NH3 in MeOH in DCM. Further purification by normal phase chromatography eluting with 0-100% ethyl acetate in cyclohexane followed by MDAP (acidic conditions), afforded the title compound (190 mg).

後処理

  1. customAt this point, the four reaction mixtures
  2. concentrationconcentrated
  3. washeluting with MeOH (250 mL)
  4. concentrationThe basic methanolic solution was concentrated
  5. custompurified by normal phase chromatography
  6. washeluting with 0-10% 2M NH3 in MeOH in DCM
  7. customFurther purification by normal phase chromatography
  8. washeluting with 0-100% ethyl acetate in cyclohexane

出典と根拠

ORDレコード
ord-34d9877a71544c58a09d7aa9999fbf57
出典データセット
uspto-grants-2015_05
特許番号
US09029545B2

反応ノート

読み込み中…