Water → HCID 54674989、化合物

HRID 2095662

反応式

HRID 2095662 の反応式
Br[C:2]1[C:3]([CH3:11])=[N:4][N:5]([CH3:10])[C:6]=1[C:7]([OH:9])=O.[NH4+].[Cl-].C[N:15](C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.CN(C=O)C.[Cl:50][C:51]1[C:56]([F:57])=[CH:55][CH:54]=[C:53]([O:58][CH3:59])[C:52]=1[C@H:60]([C:62]1[C:70]2[C:65](=[N:66][CH:67]=[C:68](B3OC(C)(C)C(C)(C)O3)[CH:69]=2)[NH:64][CH:63]=1)[CH3:61].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:50][C:51]1[C:56]([F:57])=[CH:55][CH:54]=[C:53]([O:58][CH3:59])[C:52]=1[C@H:60]([C:62]1[C:70]2[C:65](=[N:66][CH:67]=[C:68]([C:2]3[C:3]([CH3:11])=[N:4][N:5]([CH3:10])[C:6]=3[C:7]([NH2:15])=[O:9])[CH:69]=2)[NH:64][CH:63]=1)[CH3:61]

参加物

11

反応物 8

HCID 962WaterHCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 27798334-bromo-1,3-dimethyl-1H-pyrazole-5-carboxylic acidHCID 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 54674989HCID 54674989、化合物

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

実験手順

A mixture of 4-bromo-1,3-dimethyl-1H-pyrazole-5-carboxylic acid (20.0 mg, 0.0913 mmol), NH4Cl (48.8 mg, 0.913 mmol), TBTU (58.6 mg, 0.183 mmol), DIPEA (0.159 mL, 0.913 mmol) and DMF (2 mL, 20 mmol) was stirred at rt for 10 min. 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 (3.34 mg, 0.00456 mmol), K2CO3 (18.9 mg, 0.137 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=7.3 Hz, 3H), 2.04 (s, 3H), 3.66 (br. s., 3H), 3.95 (s, 3H), 5.11 (q, J=6.8 Hz, 1H), 6.90 (dd, J=9.0, 4.2 Hz, 1H), 7.08 (t, J=8.8 Hz, 1H), 7.37 (d, J=1.3 Hz, 1H), 7.45 (s, 1H), 8.07 (br. s., 1H). MS (ES+): m/z=442.14/444.14 (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-8e78ff9f52a74ddba6c4ae939067f1c8
出典データセット
uspto-grants-2013_05
特許番号
US08445510B2

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