Water → (4-{3-[(1S)-1-(2-Chloro-3-fluoro-6-methoxyphenyl)ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-1-methyl-1H-pyrazol-5-yl)methanol

HRID 2095665

反応式

HRID 2095665 の反応式
Br[C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]([OH:10])=O.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[CH:6]=[N:5][N:4]([CH3:7])[C:3]=3[CH2:8][OH:10])[CH:41]=2)[NH:36][CH:35]=1)[CH3:33]

参加物

9

反応物 6

HCID 962WaterHCID 8028Tetrahydrofuran2 回HCID 11430Potassium CarbonateHCID 6736864-Bromo-1-methyl-1H-pyrazole-5-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

生成物 1

HCID 54674987(4-{3-[(1S)-1-(2-Chloro-3-fluoro-6-methoxyphenyl)ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-1-methyl-1H-pyrazol-5-yl)methanol

試薬・触媒・溶媒 2

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

反応条件

温度
60 °C

実験手順

To a solution of 4-bromo-2-methyl-2H-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), 3.67 (br. s., 3H), 3.96 (s, 3H), 4.55 (s, 2H), 5.08-5.17 (m, 1H), 6.90 (dd, J=9.1, 4.3 Hz, 1H), 7.08 (t, J=8.8 Hz, 1H), 7.34 (d, J=1.3 Hz, 1H), 7.46 (s, 1H), 7.53 (s, 1H), 8.15-8.22 (m, 1H). MS (ES+): m/z=415.13/417.13 (100/50) [MH+]. HPLC: tR=1.37 min (polar—3 min, UPLC-ACQUITY).

後処理

  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

出典と根拠

ORDレコード
ord-1c0af1c6a3194b4fade5bbeb6e63cdaf
出典データセット
uspto-grants-2013_05
特許番号
US08445510B2

関連ノート

読み込み中…