Water → HCID 54674988, 화합물

HRID 2095663노트

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HRID 2095663 반응식
Br[C:2]1[C:3]([C:8]([OH:10])=O)=[N:4][N:5]([CH3:7])[CH:6]=1.C1COCC1.B.C1COCC1.[Cl:22][C:23]1[C:28]([F:29])=[CH:27][CH:26]=[C:25]([O:30][CH3:31])[C:24]=1[C@H:32]([C:34]1[C:42]2[C:37](=[N:38][CH:39]=[C:40](B3OC(C)(C)C(C)(C)O3)[CH:41]=2)[NH:36][CH:35]=1)[CH3:33].C([O-])([O-])=O.[K+].[K+].O>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O1CCOCC1>[Cl:22][C:23]1[C:28]([F:29])=[CH:27][CH:26]=[C:25]([O:30][CH3:31])[C:24]=1[C@H:32]([C:34]1[C:42]2[C:37](=[N:38][CH:39]=[C:40]([C:2]3[C:3]([CH2:8][OH:10])=[N:4][N:5]([CH3:7])[CH:6]=3)[CH:41]=2)[NH:36][CH:35]=1)[CH3:33]

참가 물질

9

반응물 6

HCID 962WaterHCID 8028Tetrahydrofuran2회HCID 11430Potassium CarbonateHCID 5360134-bromo-1-methyl-1H-pyrazole-3-carboxylic acidHCID 2723981Borane;tetrahydrofuranHCID 670040713-[(S)-1-(2-chloro-3-fluoro-6-methoxyphenyl)-ethyl]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine

생성물 1

HCID 54674988HCID 54674988, 화합물

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 312751,4-Dioxane용매

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온도
60 °C

실험 절차

To a solution of 4-bromo-1-methyl-1H-pyrazole-3-carboxylic acid (20.0 mg, 0.0976 mmol) in THF (3 mL, 40 mmol) was added 1.0 M of BH3.THF in THF (0.49 mL, 0.49 mmol), and the resulting solution was heated to 60° C. overnight. The material was extracted with EtOAc and washed with sat. NaHCO3 (3×) to remove carboxylic acid starting material. The organic layer was concentrated in vacuo. 3-[(S)-1-(2-Chloro-3-fluoro-6-methoxyphenyl)-ethyl]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (15.0 mg, 0.0348 mmol), (1,1′bis-(diphenylphosphino)-ferrocene) palladium dichloride (3.57 mg, 0.00488 mmol), K2CO3 (20.2 mg, 0.146 mmol) and 4:1 dioxane:H2O (1 mL, 10 mmol) were added, and the mixture was heated to 95° C. for 30 min. The solution was used directly for HPLC purification, and the fractions containing the pure product were concentrated in vacuo to afford the title compound as a white solid. 1H NMR (400 MHz, CD3OD): δ=1.80 (d, J=7.1 Hz, 3H), 3.68 (br. s., 3H), 3.90 (s, 3H), 4.45-4.55 (m, 2H), 5.10-5.16 (m, 1H), 6.89 (dd, J=9.1, 4.3 Hz, 1H), 7.07 (t, J=8.8 Hz, 1H), 7.31 (d, J=1.3 Hz, 1H), 7.65 (s, 1H), 7.68 (s, 1H), 8.27 (br. s., 1H). MS (ES+): m/z=415.12/417.13 (100/50) [MH+]. HPLC: tR=1.35 min (polar—3 min, UPLC-ACQUITY).

후처리

  1. extractionThe material was extracted with EtOAc
  2. washwashed with sat. NaHCO3 (3×)
  3. customto remove carboxylic acid starting material
  4. concentrationThe organic layer was concentrated in vacuo
  5. temperaturethe mixture was heated to 95° C. for 30 min
  6. customThe solution was used directly for HPLC purification
  7. additionthe fractions containing the pure product
  8. concentrationwere concentrated in vacuo

출처 및 근거

ORD 기록
ord-d52e6d45cde34903b06a864735aaccf7
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08445510B2

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