Sodium Carbonate → HCID 71143903, 화합물

HRID 2173101노트

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HRID 2173101 반응식
[C:1]([O:5][C:6]([NH:8][C@@H:9]1[C@H:14]([NH:15][C:16]2[N:21]=[C:20](Cl)[C:19]3[C:23](=[O:33])[N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:25][C:18]=3[C:17]=2[F:34])[CH2:13][CH2:12][O:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[B-](F)(F)(F)[CH2:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.[K+].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:1]([O:5][C:6]([NH:8][C@@H:9]1[C@H:14]([NH:15][C:16]2[N:21]=[C:20]([CH2:36][CH2:37][C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[C:19]3[C:23](=[O:33])[N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:25][C:18]=3[C:17]=2[F:34])[CH2:13][CH2:12][O:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

7

반응물 3

HCID 10340Sodium CarbonateHCID 23697312Potassium trifluoro(2-phenylethyl)borate(1-)HCID 86654748tert-Butyl 6-((3R,4R)-3-(tert-butoxycarbonylamino)tetrahydro-2H-pyran-4-ylamino)-4-chloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate

생성물 1

HCID 71143903HCID 71143903, 화합물

시약·촉매·용매 3

HCID 178418476HCID 178418476, 화합물촉매HCID 962Water용매HCID 312751,4-Dioxane용매

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온도
85 °C

실험 절차

In a 30 mL sealed cap glass vial, tert-butyl 6-((3R,4R)-3-(tert-butoxycarbonylamino)tetrahydro-2H-pyran-4-ylamino)-4-chloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate (150 mg, 0.299 mmol), potassium trifluoro(phenethyl)borate (76 mg, 0.359 mmol) and PdCl2(PPh3)2 (42.0 mg, 0.060 mmol) were dissolved in dioxane (5 mL). To the reaction mixture was added 2N aqueous sodium carbonate solution (2.0 mL). The cap was sealed and the reaction mixture was heated at 85° C. for 3 hours. The reaction mixture was subsequently diluted with water (5 mL) and extracted with EtOAc (2×30 mL). The combined organic phase was dried over sodium sulfate and evaporated to give the intermediate, tert-butyl 6-(((3R,4R)-3-((tert-butoxycarbonyl)amino)tetrahydro-2H-pyran-4-yl)amino)-7-fluoro-3-oxo-4-phenethyl-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate, which was treated with TFA (4 mL) at room temperature for 1 hour to remove the protecting groups. TFA was subsequently evaporated from the reaction mixture. The residual material was dissolved in DMSO (8 mL) and purified by preparative HPLC, eluting with a gradient of 20-55% ACN (0.035% TFA) and water (0.05% TFA). The pure product fractions were combined, evaporated to a minimal volume, and lyophilized to give a TFA salt of the title compound as a light yellow solid (42 mg, 38%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.58-1.75 (m, 1H), 1.95-2.17 (m, 1H), 2.83-3.04 (m, 2H), 3.16-3.32 (m, 1H), 3.32-3.46 (m, 1H), 3.47-3.61 (m, 1H), 3.66 (d, J=11.37 Hz, 1H), 3.83-4.03 (m, 2H), 4.22-4.39 (m, 3H), 6.99 (d, J=5.05 Hz, 1H), 7.09-7.33 (m, 5H), 7.93 (br s, 2H), 8.32 (s, 1H). ESI-MS m/z [M+H]+ calc'd for C20H23FN4O2, 371. found, 371.

후처리

  1. customIn a 30 mL sealed
  2. customThe cap was sealed
  3. extractionextracted with EtOAc (2×30 mL)
  4. dry with materialThe combined organic phase was dried over sodium sulfate
  5. customevaporated

출처 및 근거

ORD 기록
ord-935a27c8419b44eca4fd87a23d67b8d2
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09056873B2

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