Sodium Carbonate → HCID 90284557, 화합물

HRID 2173100노트

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HRID 2173100 반응식
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]1[NH:15][C:16]1[N:21]=[C:20](Cl)[C:19]2[C:23](=[O:33])[N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:25][C:18]=2[C:17]=1[F:34])=[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[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]1[NH:15][C:16]1[N:21]=[C:20]([CH2:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:19]2[C:23](=[O:33])[N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:25][C:18]=2[C:17]=1[F:34])=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

7

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HCID 10340Sodium CarbonateHCID 23697312Potassium trifluoro(2-phenylethyl)borate(1-)HCID 86654740tert-Butyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-chloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate

생성물 1

HCID 90284557HCID 90284557, 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-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-chloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate (150 mg, 0.301 mmol), potassium trifluoro(phenethyl)borate (76 mg, 0.361 mmol) and PdCl2(PPh3)2 (42.2 mg, 0.060 mmol) were dissolved in dioxane (5 mL). To the reaction mixture was added 2N aqueous sodium carbonate solution (2 mL). The cap was sealed and the reaction mixture was heated at 85° C. for 2 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-(((1R,2S)-2-((tert-butoxycarbonyl)amino)cyclohexyl)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 25-40% 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 white solid (21 mg, 19%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.41 (br s, 2H), 1.65 (br s, 2H), 1.68-1.81 (m, 2H), 1.84 (br s, 2H), 2.83-3.04 (m, 2H), 3.14-3.41 (m, 2H), 4.22-4.43 (m, 3H), 6.65 (d, J=6.82 Hz, 1H), 7.08-7.33 (m, 4H), 7.37 (br s, 1H), 7.54 (br s, 1H), 7.70 (br s, 3H), 8.31 (s, 1H). ESI-MS m/z [M+H]+ calc'd for C21H25FN4O, 369. found, 369.

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-1c08caf8ebce4bd480c0ce4c371389fd
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09056873B2

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