Water → HCID 54674989, 화합물

HRID 2095662

반응식

HRID 2095662 반응식
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]

참가 물질

11

반응물 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

생성물 1

HCID 54674989HCID 54674989, 화합물

시약·촉매·용매 2

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

실험 절차

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).

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-8e78ff9f52a74ddba6c4ae939067f1c8
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08445510B2

연결된 노트

불러오는 중…