Trifluoroacetic acid → HCID 86590836, 화합물

HRID 720670노트

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HRID 720670 반응식
[CH:1]1([CH2:4][N:5]2[C:13]3[N:12]=[C:11]([CH2:14][C:15]4[CH:20]=[CH:19][C:18]([N:21]([CH3:50])[C:22]([C:24]5[S:28][C:27]([NH:29]C(C6C=CC=CC=6)(C6C=CC=CC=6)C6C=CC=CC=6)=[N:26][C:25]=5[CH3:49])=[O:23])=[CH:17][CH:16]=4)[NH:10][C:9]=3[C:8](=[O:51])[N:7]([CH2:52][C:53]3[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=3[F:59])[C:6]2=[O:60])[CH2:3][CH2:2]1.FC(F)(F)C(O)=O.C([SiH](CC)CC)C>ClCCl>[CH:1]1([CH2:4][N:5]2[C:13]3[N:12]=[C:11]([CH2:14][C:15]4[CH:16]=[CH:17][C:18]([N:21]([CH3:50])[C:22]([C:24]5[S:28][C:27]([NH2:29])=[N:26][C:25]=5[CH3:49])=[O:23])=[CH:19][CH:20]=4)[NH:10][C:9]=3[C:8](=[O:51])[N:7]([CH2:52][C:53]3[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=3[F:59])[C:6]2=[O:60])[CH2:3][CH2:2]1

참가 물질

5

반응물 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 86590835HCID 86590835, 화합물

생성물 1

HCID 86590836HCID 86590836, 화합물수율 5.8%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

반응 조건

온도
25 °C

실험 절차

A solution of 4-methyl-2-(trityl-amino)-thiazole-5-carboxylic acid {4-[3-cyclopropylmethyl-1-(2-fluoro-benzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-methyl-amide (74.0 mg, 0.09 mmol) in dichloromethane (1.0 mL) at 25° C. was treated with trifluoroacetic acid (1.0 mL). The reaction was stirred at 25° C. for 1 h. At this time, the reaction was treated with triethylsilane (16 μL, 0.10 mmol). The reaction was concentrated in vacuo. The resulting residue was purified by HPLC (15–60% acetonitrile/water (0.075% trifluoroacetic acid in both solvents) over 40 min). Fractions with the desired product were combined and concentrated in vacuo. The resulting residue was diluted with dichloromethane (100 mL) and was washed with a saturated aqueous sodium bicarbonate solution (25 mL). The aqueous layer was re-extracted with dichloromethane (1×50 mL). The combined organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting solid was dried in vacuo for 24 h to afford 2-amino-4-methyl-thiazole-5-carboxylic acid {4-[3-cyclopropylmethyl-1-(2-fluoro-benzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-methyl-amide (3.0 mg, 5.8%) as a white solid: (ES)+-HRMS m/e calcd for C29H28N7O3SF (M+H)+ 574.2031, found 574.2035.

후처리

  1. concentrationThe reaction was concentrated in vacuo
  2. customThe resulting residue was purified by HPLC (15–60% acetonitrile/water (0.075% trifluoroacetic acid in both solvents) over 40 min)
  3. concentrationconcentrated in vacuo
  4. additionThe resulting residue was diluted with dichloromethane (100 mL)
  5. washwas washed with a saturated aqueous sodium bicarbonate solution (25 mL)
  6. extractionThe aqueous layer was re-extracted with dichloromethane (1×50 mL)
  7. dry with materialThe combined organics were dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe resulting solid was dried in vacuo for 24 h

출처 및 근거

ORD 기록
ord-eca7dd3bcf624ea18b6e7f9660698d5e
출처 데이터셋
uspto-grants-2006_11
특허 번호
US07135475B2

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