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

HRID 573680ノート

反応式

HRID 573680 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[CH2:54][CH2:53][O:52][CH2:51][CH2:50]3)[CH:46]=[N: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:43]4[CH:48]=[N:47][CH:46]=[C:45]([N:49]5[CH2:50][CH2:51][O:52][CH2:53][CH2:54]5)[CH:44]=4)[C:10]=23)(=[O:13])=[O:14])[CH:20]=[CH:19][CH:18]=1

参加物

9

反応物 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 584122914-(5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)morpholineHCID 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 683239063-Chloro-N-[6-methyl-3-[5-(4-morpholinyl)-3-pyridinyl]-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridin-4-yl]benzenesulfonamide収率 67%

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) (100 mg, 0.171 mmol), 4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinyl]morpholine (Description 81) (214 mg, 0.737 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, both mixtures were combined and concentrated. The residue was passed through an SCX cartridge, eluting with MeOH (75 mL) and then with 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, to give the title compound (65 mg). LCMS (A) m/z: 567 [M+1]+, Rt 0.72 min (acidic).

後処理

  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

出典と根拠

ORDレコード
ord-9088820950144f0faafcc6ae0dc87e5c
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…