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

HRID 2095656

反応式

HRID 2095656 の反応式
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([O:9][CH3:10])[C:3]=1[C@H:11]([C:13]1[C:21]2[C:16](=[N:17][CH:18]=[C:19](B3OC(C)(C)C(C)(C)O3)[CH:20]=2)[NH:15][CH:14]=1)[CH3:12].Br[C:32]1[C:33]([C:38]([F:41])([F:40])[F:39])=[N:34][N:35]([CH3:37])[CH:36]=1.C([O-])([O-])=O.[K+].[K+].O>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([O:9][CH3:10])[C:3]=1[C@H:11]([C:13]1[C:21]2[C:16](=[N:17][CH:18]=[C:19]([C:32]3[C:33]([C:38]([F:41])([F:40])[F:39])=[N:34][N:35]([CH3:37])[CH:36]=3)[CH:20]=2)[NH:15][CH:14]=1)[CH3:12]

参加物

7

反応物 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27946514-Bromo-1-methyl-3-(trifluoromethyl)-1H-pyrazoleHCID 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 546751313-[(1S)-1-(2-Chloro-3-fluoro-6-methoxyphenyl)ethyl]-5-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]-1H-pyrrolo[2,3-b]pyridine

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 312751,4-Dioxane溶媒

実験手順

A mixture of 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 (9.00 mg, 0.0209 mmol), 4-bromo-1-methyl-3-(trifluoromethyl)-1H-pyrazole (9.57 mg, 0.0418 mmol), Pd(PPh3)4 (1.21 mg, 0.00104 mmol), K2CO3 (0.00866 g, 0.0627 mmol) and 4:1 dioxane:H2O (0.8 mL, 8 mmol) was heated in a microwave reactor at 95° C. for 20 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=1.78 (d, J=7.1 Hz, 3H), 3.62 (br. s., 3H), 3.96 (s, 3H), 5.08 (q, J=6.9 Hz, 1H), 6.86 (dd, J=9.1, 4.3 Hz, 1H), 7.01-7.09 (m, 1H), 7.35 (d, J=1.3 Hz, 1H), 7.52 (s, 1H), 7.78 (s, 1H), 8.10 (d, J=2.0 Hz, 1H). MS (ES+): m/z=453.11/455.11 (100/50) [MH+]. HPLC: tR=1.36 min (polar—3 min, UPLC-ACQUITY).

後処理

  1. customThe solution was used directly for HPLC purification
  2. additionthe fractions containing the pure product
  3. concentrationwere concentrated in vacuo

出典と根拠

ORDレコード
ord-290c79f5fa8241728d53aff9d0ce6007
出典データセット
uspto-grants-2013_05
特許番号
US08445510B2

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