Triphenylphosphine → 1-[(3aS,4R,6aR)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-4,7-difluoro-1H-imidazo[4,5-c]pyridine

HRID 470168

반응식

HRID 470168 반응식
[CH3:1][C:2]1([CH3:11])[O:6][C@@H:5]2[CH:7]=[CH:8][C@H:9](O)[C@@H:4]2[O:3]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:31][C:32]1[C:37]2[N:38]=[CH:39][NH:40][C:36]=2[C:35]([F:41])=[CH:34][N:33]=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[CH3:1][C:2]1([CH3:11])[O:6][C@@H:5]2[CH:7]=[CH:8][C@@H:9]([N:40]3[C:36]4[C:35]([F:41])=[CH:34][N:33]=[C:32]([F:31])[C:37]=4[N:38]=[CH:39]3)[C@@H:4]2[O:3]1.[CH3:1][C:2]1([CH3:11])[O:6][C@@H:5]2[CH:7]=[CH:8][C@@H:9]([N:38]3[C:37]4[C:32]([F:31])=[N:33][CH:34]=[C:35]([F:41])[C:36]=4[N:40]=[CH:39]3)[C@@H:4]2[O:3]1

참가 물질

7

반응물 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 10909808(3aS,4S,6aR)-2,2-Dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-olHCID 178506010HCID 178506010, 화합물

생성물 2

HCID 583292881-[(3aS,4R,6aR)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-4,7-difluoro-1H-imidazo[4,5-c]pyridineHCID 583293123-[(3aS,4R,6aR)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-4,7-difluoro-3H-imidazo[4,5-c]pyridine

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
0 °C

실험 절차

(3aS,4S,6aR)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-ol (1-1) (250 mg, 1.6 mmol, 1 equiv) was dissolved in dry THF (8 mL). Triphenylphosphine (630 mg, 2.4 mmol, 1.5 equiv) was added, followed by 4,7-difluoro-1H-imidazo[4,5-c]pyridine (1-4, 300 mg, 1.9 mmol, 1.2 equiv). The mixture was cooled to 0° C. and DIAD (470 μL, 2.4 mmol, 1.5 equiv) was added dropwise. The resulting mixture was stirred at ambient temperature for 2 hours. The solvent was removed at reduced pressure and the yellow residue was purified via flash chromatography on a 80 g silica gel column (gradient elution 0 to 100% ethyl acetate in hexanes) to yield 1-[(3aS,4R,6aR)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-4,7-difluoro-1H-imidazo[4,5-c]pyridine (2-2) and 3-[(3aS,4R,6aR)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-4,7-difluoro-3H-imidazo[4,5-c]pyridine (2-1) as a 1:1 regioisomeric mixture. 1H NMR (2-2) (500 MHz, CDCl3): δ 7.82 (s, 1H); 7.86 (m, 1H); 6.42 (d, J=5.7 Hz, 1H); 6.05 (s, 1H); 5.75 (s, 1H); 5.44 (d, J=5.5 Hz, 1H); 4.68 (d, J=5.7 Hz, 1H); 1.51 (s, 3H); 1.37 (s, 3H). LRMS m/z (M+H) 294.0 found, 294.1 required. 1H NMR (2-1) (500 MHz, CDCl3): δ 7.90 (s, 1H); 7.84 (m, 1H); 6.42 (d, J=5.7 Hz, 1H); 6.05 (s, 1H); 5.75 (s, 1H); 5.44 (d, J=5.5 Hz, 1H); 4.68 (d, J=5.7 Hz, 1H); 1.51 (s, 3H); 1.37 (s, 3H). LRMS m/z (M+H) 294.0 found, 294.1 required.

후처리

  1. customThe solvent was removed at reduced pressure
  2. customthe yellow residue was purified via flash chromatography on a 80 g silica gel column (gradient elution 0 to 100% ethyl acetate in hexanes)

출처 및 근거

ORD 기록
ord-d71b5a59a29846488fbecf8cba6ccfd0
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08629275B2

연결된 노트

불러오는 중…