Acetic Acid → 1-{4-[4-(3-{(1S)-1-[2-Chloro-6-(difluoromethoxy)-3-fluorophenyl]ethyl}-1H-pyrrolo[2,3-b]pyridin-5-yl)-5-methyl-1H-pyrazol-1-yl]piperidin-1-yl}ethanone

HRID 2095729노트

반응식

HRID 2095729 반응식
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([O:9][CH:10]([F:12])[F:11])[C:3]=1[C@H:13]([C:15]1[C:23]2[C:18](=[N:19][CH:20]=[C:21]([C:24]3[CH:25]=[N:26][N:27]([CH:30]4[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]4)[C:28]=3[CH3:29])[CH:22]=2)[NH:17][CH:16]=1)[CH3:14].[C:36](O)(=[O:38])[CH3:37].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)CC)C.C(Cl)Cl>>[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([O:9][CH:10]([F:12])[F:11])[C:3]=1[C@H:13]([C:15]1[C:23]2[C:18](=[N:19][CH:20]=[C:21]([C:24]3[CH:25]=[N:26][N:27]([CH:30]4[CH2:31][CH2:32][N:33]([C:36](=[O:38])[CH3:37])[CH2:34][CH2:35]4)[C:28]=3[CH3:29])[CH:22]=2)[NH:17][CH:16]=1)[CH3:14]

참가 물질

6

반응물 5

HCID 176Acetic AcidHCID 6344DichloromethaneHCID 8471TriethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 546735943-{(1S)-1-[2-Chloro-6-(difluoromethoxy)-3-fluorophenyl]ethyl}-5-[5-methyl-1-(piperidin-4-yl)-1H-pyrazol-4-yl]-1H-pyrrolo[2,3-b]pyridine

생성물 1

HCID 546735931-{4-[4-(3-{(1S)-1-[2-Chloro-6-(difluoromethoxy)-3-fluorophenyl]ethyl}-1H-pyrrolo[2,3-b]pyridin-5-yl)-5-methyl-1H-pyrazol-1-yl]piperidin-1-yl}ethanone

실험 절차

A mixture of 3-{(1S)-1-[2-chloro-6-(difluoromethoxy)-3-fluorophenyl]ethyl}-5-[5-methyl-1-(piperidin-4-yl)-1H-pyrazol-4-yl]-1H-pyrrolo[2,3-b]pyridine (40.0 mg, 0.0794 mmol), acetic acid (23.8 mg, 0.397 mmol), TBTU (51.0 mg, 0.159 mmol), triethylamine (40.2 mg, 0.397 mmol) and DCM (4 mL, 60 mmol) was stirred at rt for 10 min. The solution was extracted with EtOAc, washed with 1 M HCl, and then sat. NaHCO3. The organic layer was concentrated in vacuo, loaded onto silica gel and purified via column chromatography. The product was eluted with 2-3% (7N NH3 in MeOH)/DCM, 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=1.84 (d, J=7.3 Hz, 3H), 1.93-2.04 (m, 3H), 2.12 (dd, J=15.4, 2.5 Hz, 1H), 2.16 (s, 3H), 2.26 (s, 3H), 2.76-2.88 (m, 1H), 3.32-3.35 (m, 1H), 4.08 (dd, J=14.0, 1.9 Hz, 1H), 4.43-4.54 (m, 1H), 4.64-4.73 (m, 1H), 5.11 (q, J=7.0 Hz, 1H), 6.43 (br. s., 1H), 7.12 (dd, J=8.8, 4.5 Hz, 1H), 7.19 (t, J=8.7 Hz, 1H), 7.38 (d, J=1.8 Hz, 1H), 7.39 (d, J=1.3 Hz, 1H), 7.48 (s, 1H), 8.13 (d, J=2.0 Hz, 1H). MS (ES+): m/z=546.17/548.18 (100/50) [MH+]. HPLC: tR=1.43 min (polar—3 min, UPLC-ACQUITY).

후처리

  1. extractionThe solution was extracted with EtOAc
  2. washwashed with 1 M HCl
  3. concentrationThe organic layer was concentrated in vacuo
  4. custompurified via column chromatography
  5. washThe product was eluted with 2-3% (7N NH3 in MeOH)/DCM
  6. additionthe fractions containing the pure product
  7. concentrationwere concentrated in vacuo

출처 및 근거

ORD 기록
ord-f5298ae7dbf34b0597a5874359b90d9e
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08445510B2

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