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

HRID 1625427노트

반응식

HRID 1625427 반응식
[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]

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 2

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

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온도
110 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-53d7033676b64f6080220e8396edb294
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08778977B2

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