Potassium Phosphate, Tribasic → N-(3-(4-(4-Amino-2-fluorophenoxy)pyrrolo[2,1-f][1,2,4]triazin-5-yl)phenyl)acetamide

HRID 347521노트

반응식

HRID 347521 반응식
CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.Cl[C:36]1[CH:37]=[CH:38][N:39]2[C:44]=1[C:43]([O:45][C:46]1[CH:51]=[CH:50][C:49]([NH2:52])=[CH:48][C:47]=1[F:53])=[N:42][CH:41]=[N:40]2.[C:54]([NH:57][C:58]1[CH:59]=[C:60](B(O)O)[CH:61]=[CH:62][CH:63]=1)(=[O:56])[CH3:55].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:52][C:49]1[CH:50]=[CH:51][C:46]([O:45][C:43]2[C:44]3=[C:36]([C:62]4[CH:63]=[C:58]([NH:57][C:54](=[O:56])[CH3:55])[CH:59]=[CH:60][CH:61]=4)[CH:37]=[CH:38][N:39]3[N:40]=[CH:41][N:42]=2)=[C:47]([F:53])[CH:48]=1

참가 물질

6

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 157274(3-Acetamidophenyl)boronic acid2회HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl2회HCID 210816684-(5-Chloropyrrolo[2,1-f][1,2,4]triazin-4-yloxy)-3-fluorobenzenamine

생성물 1

HCID 21081735N-(3-(4-(4-Amino-2-fluorophenoxy)pyrrolo[2,1-f][1,2,4]triazin-5-yl)phenyl)acetamide수율 26.5%

시약·촉매·용매 1

HCID 167845palladium(II) acetate촉매2회

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온도
80 °C

실험 절차

A flask was charged with palladium acetate (4.5 mg, 0.02 mmol), X-Phos ligand (24 mg, 0.05 mmol, Strem), 4-(5-chloropyrrolo[2,1-f][1,2,4]triazin-4-yloxy)-3-fluorobenzenamine (56 mg, 0.20 mmol), 3-acetamidobenzene boronic acid (72 mg, 0.40 mmol, Lancaster), and potassium phosphate (127 mg, 0.60 mmol) in that order. The flask was flushed with nitrogen and then t-BuOH was added (0.40 mL). The mixture was heated at 80° C. for 8 h. Additional shots of palladium acetate (4.5 mg, 0.02 mmol), X-Phos ligand (24 mg, 0.05 mmol), and 3-acetamidobenzene boronic acid (72 mg, 0.40 mmol) were added and the reaction was stirred an additional 9 h at 80° C. After cooling to rt, the reaction was filtered using MeOH to remove the potassium phosphate and then concentrated in vacuo. The crude product was purified by reverse phase prep HPLC and the appropriate fractions were concentrated in vacuo to remove MeOH. The resulting aqueous layer was made basic with saturated sodium bicarbonate solution and extracted with ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate and concentrated in vacuo to give the title compound (20 mg, 26%) as a white solid. 1H NMR (CD3OD) δ 7.84–7.94 (m, 2H), 7.44–7.41 (m, 1H), 7.34–7.19 (m, 3H), 6.92 (t, 1H, J=8.8 Hz), 6.87 (d, 1H, J=2.8 Hz), 6.50 (dd, 1H, J=12.4, 2.4 Hz), 6.46–6.43 (m, 1H), 2.04 (s, 3H); MS(ESI+) m/z 378.3 (M+H)+.

후처리

  1. customThe flask was flushed with nitrogen
  2. additiont-BuOH was added (0.40 mL)
  3. temperatureAfter cooling to rt
  4. filtrationthe reaction was filtered
  5. customto remove the potassium phosphate
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by reverse phase prep HPLC
  8. concentrationthe appropriate fractions were concentrated in vacuo
  9. customto remove MeOH
  10. extractionextracted with ethyl acetate
  11. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  12. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-6022cfc4908448c5a6a91a86fea16cd7
출처 데이터셋
uspto-grants-2007_02
특허 번호
US07173031B2

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