Dichloromethane → [5-(1H-Pyrrolo[2,3-b]pyridin-3-yl)-thiophen-2-ylmethyl]-carbamic acid tert-butyl ester

HRID 1625427ノート

反応式

HRID 1625427 の反応式
[C:1]([O:5][C:6](=[O:15])[NH:7][CH2:8][C:9]1[S:10][C:11](Br)=[CH:12][CH:13]=1)([CH3:4])([CH3:3])[CH3:2].C(OC([N:23]1[C:27]2=[N:28][CH:29]=[CH:30][CH:31]=[C:26]2[C:25](B2OC(C)(C)C(C)(C)O2)=[CH:24]1)=O)(C)(C)C.ClCCl.O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+]>O.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]>[C:1]([O:5][C:6](=[O:15])[NH:7][CH2:8][C:9]1[S:10][C:11]([C:25]2[C:26]3[C:27](=[N:28][CH:29]=[CH:30][CH:31]=3)[NH:23][CH:24]=2)=[CH:12][CH:13]=1)([CH3:4])([CH3:3])[CH3:2]

参加物

8

反応物 5

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 2779810tert-Butyl ((5-bromothiophen-2-yl)methyl)carbamateHCID 53217196tert-Butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate

生成物 1

HCID 59362564[5-(1H-Pyrrolo[2,3-b]pyridin-3-yl)-thiophen-2-ylmethyl]-carbamic acid tert-butyl ester

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒

反応条件

温度
110 °C

実験手順

Into a vial was dissolved (5-bromo-thiophen-2-ylmethyl)-carbamic acid tert-butyl ester (115 mg, 0.000394 mol; Maybridge), 3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrrolo[2,3-b]pyridine-1-carboxylic acid tert-butyl ester (119 mg, 0.000346 mol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (28 mg, 0.000034 mol; Strem) in 1,4-dioxane (6.0 mL, 0.077 mol; Acros). To this was added 2.0 M of sodium carbonate in water (1.5 mL). The reaction was purged with Ar and sealed. The reaction was heated at 110° C. under an atmosphere of Argon for 2 hours. The reaction was diluted with methylene chloride and washed with water. The organic layer was dried with magnesium sulfate, filtered and evaporated. The residue was taken up in DMSO and purified by preparative HPLC to yield the title compound in 33.4 mg yield (22%) as the TFA salt. MS m/z=330.15 (M+1). 1H NMR (400 MHz, CDCl3)™ ppm 13.919 (s, 1H) 8.703 (dd, J=7.9, 1.1 Hz, 1H) 8.246 (dd, J=5.7, 1.0 Hz, 1H) 7.676 (d, J=1.7 Hz, 1H) 7.464 (dd, J=7.9, 5.8 Hz, 1H) 7.111 (d, J=3.6 Hz, 1H) 6.985 (d, J=3.6 Hz, 1H) 4.981 (s (br), 1H) 4.508 (d, J=5.7 Hz, 2H) 1.485 (s, 9H).

後処理

  1. customThe reaction was purged with Ar
  2. customsealed
  3. additionThe reaction was diluted with methylene chloride
  4. washwashed with water
  5. dry with materialThe organic layer was dried with magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. custompurified by preparative HPLC

出典と根拠

ORDレコード
ord-53d7033676b64f6080220e8396edb294
出典データセット
uspto-grants-2014_07
特許番号
US08778977B2

反応ノート

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