Potassium Phosphate, Tribasic → methyl 3-((5-chloro-2-(5-fluoro-1-trityl-1H-pyrazolo[3,4-b]pyridin-3-yl)pyrimidin-4-yl)amino)bicyclo[2.2.2]octane-2-carboxylate

HRID 539922ノート

反応式

HRID 539922 の反応式
Cl[C:2]1[N:7]=[C:6]([NH:8][CH:9]2[CH:14]3[CH2:15][CH2:16][CH:11]([CH2:12][CH2:13]3)[CH:10]2[C:17]([O:19][CH3:20])=[O:18])[C:5]([Cl:21])=[CH:4][N:3]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[F:30][C:31]1[CH:32]=[C:33]2[C:39](B3OC(C)(C)C(C)(C)O3)=[N:38][N:37]([C:49]([C:62]3[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=3)([C:56]3[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=3)[C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)[C:34]2=[N:35][CH:36]=1.B([O-])[O-]>O.C1COCC1.CCOC(C)=O.C(Cl)Cl.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:21][C:5]1[C:6]([NH:8][CH:9]2[CH:14]3[CH2:15][CH2:16][CH:11]([CH2:12][CH2:13]3)[CH:10]2[C:17]([O:19][CH3:20])=[O:18])=[N:7][C:2]([C:39]2[C:33]3[C:34](=[N:35][CH:36]=[C:31]([F:30])[CH:32]=3)[N:37]([C:49]([C:50]3[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=3)([C:56]3[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=3)[C:62]3[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=3)[N:38]=2)=[N:3][CH:4]=1

参加物

10

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 679757175-Fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-trityl-1H-pyrazolo[3,4-b]pyridineHCID 86707194Methyl 3-((2,5-dichloropyrimidin-4-yl)amino)-bicyclo-[2.2.2]octane-2-carboxylateHCID 178514824HCID 178514824、化合物

生成物 1

HCID 86707193methyl 3-((5-chloro-2-(5-fluoro-1-trityl-1H-pyrazolo[3,4-b]pyridin-3-yl)pyrimidin-4-yl)amino)bicyclo[2.2.2]octane-2-carboxylate収率 83%

試薬・触媒・溶媒 5

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒2 回

反応条件

温度
90 °C

実験手順

A solution of (+/−)-trans-(2,3)-methyl 3-((2,5-dichloropyrimidin-4-yl)amino)-bicyclo-[2.2.2]octane-2-carboxylate, 37, (0.50 g, 1.51 mmol) and K3PO4 (0.96 g, 4.54 mmol) in water (2.5 mL) and THF (10.00 mL) was degassed for 15 min with a stream of nitrogen. Then, 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-trityl-pyrazolo[3,4-b]pyridine, 6, (0.84 g, 1.67 mmol) was added and the mixture was degassed for an additional 15 min. Then, Pd(PPh3)4 (0.09 g, 0.08 mmol) was added to the mixture. The vessel was sealed and heated to 90° C. After 2.5 hr., an additional 0.1 equivalent of boronate, 6, was added and the mixture was heated for an additional 30 min. The cooled solution was diluted with EtOAc, washed with water, dried over Na2SO4, filtered and concentrated in vacuo. Flash chromatography (SiO2, 0-35% EtOAc in DCM) gave the desired product (0.85 g, 83% yield) which was sufficiently pure for use in the next reaction: LC/MS Gradient 10-90%, 0.1% formic 5 min, C18/ACN, RT=3.85 min, (M+H) 673.27.

後処理

  1. customthe mixture was degassed for an additional 15 min
  2. customThe vessel was sealed
  3. temperaturethe mixture was heated for an additional 30 min
  4. washwashed with water
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-bd525aa0983d435a95cbcdd02603b08f
出典データセット
uspto-grants-2014_10
特許番号
US08871774B2

反応ノート

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