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Dichloromethane → PF-04880594

HRID 500734
ノート
印刷プレビュー

反応式

HRID 500734 の反応式
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]3[CH:17]=[CH:16][NH:15][C:12]3=[N:13][CH:14]=2)O1.BrC1C=C2C=CNC2=NC=1.[F:29][CH:30]([F:49])[CH2:31][N:32]1[CH:36]=[C:35]([C:37]2[CH:42]=[CH:41][N:40]=[C:39]([NH:43][CH2:44][CH2:45][C:46]#[N:47])[N:38]=2)[C:34](I)=[N:33]1.[F-].[Cs+].ClCCl>COCCOC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:49][CH:30]([F:29])[CH2:31][N:32]1[CH:36]=[C:35]([C:37]2[CH:42]=[CH:41][N:40]=[C:39]([NH:43][CH2:44][CH2:45][C:46]#[N:47])[N:38]=2)[C:34]([C:9]2[CH:10]=[C:11]3[CH:17]=[CH:16][NH:15][C:12]3=[N:13][CH:14]=2)=[N:33]1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

8

反応物 5

HCID 6344DichloromethaneHCID 25953Cesium fluorideHCID 103079325-bromo-1H-pyrrolo[2,3-b]pyridineHCID 242087895-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo(2,3-b)pyridineHCID 57856249HCID 57856249、化合物

生成物 1

HCID 53356806PF-04880594

試薬・触媒・溶媒 2

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒
HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
80 °C

実験手順

A mixture of the 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine B-33-4, which was prepared from 5-bromo-1H-pyrrolo[2,3-b]pyridine according to known literature methods, (145 mg, 0.594 mmol), 3-({4-[1-(2,2-difluoroethyl)-3-iodo-1H-pyrazol-4-yl]pyrimidin-2-yl}amino)propanenitrile (200 mg, 0.495 mmol), and cesium fluoride (1.48 mL of a 1M aqueous solution) in 3 mL of DME was deoxygenated with a nitrogen bubbler for 5 min and then [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) 1:1 complex with dichloromethane (41 mg, 0.05 mmol) was added. The mixture was then heated in a microwave reactor at 80° C. for 2.5 hours. The reaction was degassed and fresh catalyst (20 mg) was added. The mixture was heated in the microwave at 80° C. for 4 more hours. The resulting dark mixture was partitioned between ethyl acetate and brine. The aqueous layer was extracted twice with ethyl acetate. The combined organics were washed with brine, dried over Magnesium sulfate and reduced to minimum volume. The residue was purified on silica gel using a gradient of 0-8% methanol (containing 10% ammonium hydroxide) in a mixture of tert-butyl methyl ether and dichloromethane (1:1) to give the desired product as a pale orange solid. This material was triturated twice with tert-butyl methyl ether to give 82 mg (42%) of analytically pure 3-({4-[1-(2,2-difluoroethyl)-3-(1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-4-yl]pyrimidin-2-yl}amino)propanenitrile as an off white solid. 1H NMR (400 MHz, ACETONITRILE-d3) δ ppm 9.73 (br. s., 1H), 8.37 (d, J=2.02 Hz, 1H), 8.22 (s, 1H), 8.10 (d, J=5.31 Hz, 1H), 8.08 (d, J=1.52 Hz, 1H), 7.35-7.46 (m, 1H), 6.54 (d, J=3.79 Hz, 1H), 6.51 (dd, J=3.54, 2.02 Hz, 1H), 6.30 (tt, J=55.04, 3.82 Hz, 1H), 5.91 (br. t, J=6.82 Hz, 1H), 4.62 (td, J=14.65, 3.79 Hz, 2H), 3.39 (br. s., 2H), 2.40 (br. s., 2H).

後処理

  1. customwas deoxygenated with a nitrogen bubbler for 5 min
  2. customThe reaction was degassed
  3. additionfresh catalyst (20 mg) was added
  4. temperatureThe mixture was heated in the microwave at 80° C. for 4 more hours
  5. customThe resulting dark mixture was partitioned between ethyl acetate and brine
  6. extractionThe aqueous layer was extracted twice with ethyl acetate
  7. washThe combined organics were washed with brine
  8. dry with materialdried over Magnesium sulfate
  9. customThe residue was purified on silica gel using a gradient of 0-8% methanol (containing 10% ammonium hydroxide)
  10. additionin a mixture of tert-butyl methyl ether and dichloromethane (1:1)

出典と根拠

ORDレコード
ord-f0ccbbc2c8ad4a0d8665ee1c82edae29
出典データセット
uspto-grants-2010_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07772246B2

反応ノート

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