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 573681ノート

反応式

HRID 573681 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.[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

参加物

9

反応物 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

生成物 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}benzenesulfonamide収率 64.7%

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) (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).

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
  6. customfurther purified by MDAP (acidic conditions)

出典と根拠

ORDレコード
ord-abb9311e331142e496ac66d2c696e78f
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…