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Tetrahydrofuran → HCID 118061539, 화합물

HRID 920758
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HRID 920758 반응식
[F:1][CH:2]([F:12])[O:3][CH2:4][C@@H:5]1[CH2:8][CH2:7][C@H:6]1C(O)=O.C1C=CC(P([N:27]=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.[Cl:30][C:31]1[CH:32]=[C:33]([C:38]2[C:46]([C:47]([NH2:49])=[O:48])=[C:41]3[CH2:42][NH:43][CH2:44][CH2:45][N:40]3[N:39]=2)[CH:34]=[CH:35][C:36]=1[F:37].C1[CH2:54][O:53]CC1>C1(C)C=CC=CC=1.C(OCC)(=O)C>[Cl:30][C:31]1[CH:32]=[C:33]([C:38]2[C:46]([C:47]([NH2:49])=[O:48])=[C:41]3[CH2:42][N:43]([C:54]([NH:27][C@@H:6]4[CH2:7][CH2:8][C@H:5]4[CH2:4][O:3][CH:2]([F:1])[F:12])=[O:53])[CH2:44][CH2:45][N:40]3[N:39]=2)[CH:34]=[CH:35][C:36]=1[F:37]
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참가 물질

7

반응물 4

HCID 8028TetrahydrofuranHCID 199401P,P-Diphenylphosphinic azideHCID 1180616272-(3-Chloro-4-fluorophenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-carboxamideHCID 118061920HCID 118061920, 화합물

생성물 1

HCID 118061539HCID 118061539, 화합물수율 20%

시약·촉매·용매 2

HCID 1140
Toluene
용매
HCID 8857Ethyl Acetate용매

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온도
70 °C

실험 절차

A stirred solution of Intermediate 241B (18.34 mg, 0.102 mmol) in toluene (1 mL) at RT under nitrogen was added TEA (0.043 mL, 0.305 mmol), DPPA (0.047 mL, 0.204 mmol) and the reaction mixture was heated at 70° C. for 2 h. The reaction mass was cooled to RT and to it was added a solution of Intermediate 185B (30 mg, 0.102 mmol) in THF (1 mL) and stirred for 16 h. The reaction mass was diluted with ethyl acetate (5 mL) and the organic layer was separated. The organic layer was washed sequentially with an aqueous solution of 10% NaHCO3, water, and brine, then dried over Na2SO4, filtered and the filtrate concentrated under reduced pressure. The crude product was purified by preparative HPLC to afford Compound 241 as pale yellow solid (10 mg, 20% yield). The HPLC Retention times are 1.453 min. and 1.467 min. (Methods J and K respectively); MS(ES): m/z=472.2[M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.85 (dd, J=7.28, 2.13 Hz, 1H), 7.69 (ddd, J=8.63, 4.80, 2.13 Hz, 1H), 7.39-7.52 (m, 1H), 7.11-7.33 (2bs, 2H), 7.10 (d, J=7.34 Hz, 1H), 6.36-6.88 (m, 1H), 4.73 (s, 2H), 4.13 (t, J=5.27 Hz, 2H), 3.72-3.99 (m, 5H), 2.00-2.16 (m, 1H), 1.68-1.94 (m, 2H), 1.33-1.53 (m, 1H).

후처리

  1. temperatureThe reaction mass was cooled to RT and to it
  2. customthe organic layer was separated
  3. washThe organic layer was washed sequentially with an aqueous solution of 10% NaHCO3, water, and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated under reduced pressure
  7. customThe crude product was purified by preparative HPLC

출처 및 근거

ORD 기록
ord-e925641210974c84a1e3e5788fd73bf5
출처 데이터셋
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09273058B2

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