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4-Methylphenyl isocyanate → (2S)-2-(tert-butoxy)-2-(7-(8-fluoro-5-methylchroman-6-yl)-5-methyl-2-(3-(p-tolyl)ureido)pyrazolo[1,5-a]pyrimidin-6-yl)acetic acid

HRID 1468752
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인쇄 미리보기

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HRID 1468752 반응식
[NH2:1][C:2]1[CH:32]=[C:5]2[N:6]=[C:7]([CH3:31])[C:8]([C@H:22]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[C:23]([OH:25])=[O:24])=[C:9]([C:10]3[C:11]([CH3:21])=[C:12]4[C:17](=[C:18]([F:20])[CH:19]=3)[O:16][CH2:15][CH2:14][CH2:13]4)[N:4]2[N:3]=1.[N:33]([C:36]1[CH:41]=[CH:40][C:39]([CH3:42])=[CH:38][CH:37]=1)=[C:34]=[O:35].CCN(C(C)C)C(C)C>C1COCC1>[C:27]([O:26][C@@H:22]([C:8]1[C:7]([CH3:31])=[N:6][C:5]2[N:4]([N:3]=[C:2]([NH:1][C:34]([NH:33][C:36]3[CH:41]=[CH:40][C:39]([CH3:42])=[CH:38][CH:37]=3)=[O:35])[CH:32]=2)[C:9]=1[C:10]1[C:11]([CH3:21])=[C:12]2[C:17](=[C:18]([F:20])[CH:19]=1)[O:16][CH2:15][CH2:14][CH2:13]2)[C:23]([OH:25])=[O:24])([CH3:28])([CH3:29])[CH3:30]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

5

반응물 3

HCID 693254-Methylphenyl isocyanateHCID 81531DiisopropylethylamineHCID 71730302(2S)-2-(2-amino-7-(8-fluoro-5-methylchroman-6-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetic acid

생성물 1

HCID 71730820(2S)-2-(tert-butoxy)-2-(7-(8-fluoro-5-methylchroman-6-yl)-5-methyl-2-(3-(p-tolyl)ureido)pyrazolo[1,5-a]pyrimidin-6-yl)acetic acid

시약·촉매·용매 1

HCID 8028
Tetrahydrofuran
용매

실험 절차

A mixture of Example 1 (22 mg, 0.050 mmol), 1-isocyanato-4-methylbenzene (7.28 mg, 0.055 mmol), Hunig's base (0.026 mL, 0.149 mmol) in THF (2 mL) was stirred at rt for 16 h. It was then concentrated and purified by prep HPLC (TFA/MeOH). The fractions were combined and adjusted pH=6 using 1N NaOH. The residue was adjusted pH=3-4 by adding 1-2 drops of 1N HCl. It was then extracted with EtOAc, dried, filtered and concentrated to obtained Example (18 mg, 60%) as light yellow solid. LCMS (M+H)=576.31.

후처리

  1. concentrationIt was then concentrated
  2. custompurified by prep HPLC (TFA/MeOH)
  3. additionby adding 1-2 drops of 1N HCl
  4. extractionIt was then extracted with EtOAc
  5. customdried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto obtained Example (18 mg, 60%) as light yellow solid

출처 및 근거

ORD 기록
ord-33de800432b7427c933889252bd688ba
출처 데이터셋
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09006235B2

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