Hydroxyamine hydrochloride → HCID 136391029, 화합물

HRID 1256218노트

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HRID 1256218 반응식
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[C:18]2[CH:17]=[C:16]([CH:19]=O)[CH:15]=[CH:14][C:13]=2[C:12]2[N:21]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:42])([CH3:41])[CH3:40])[N:22]=[C:23]([NH:24][CH:25]3[CH2:30][CH2:29][N:28]([S:31]([CH3:34])(=[O:33])=[O:32])[CH2:27][CH2:26]3)[C:11]=2[N:10]=1.Cl.[NH2:44][OH:45]>N1C=CC=CC=1.CCOC(C)=O>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[C:9]1[C:18]2[CH:17]=[C:16]([CH:19]=[N:44][OH:45])[CH:15]=[CH:14][C:13]=2[C:12]2[N:21]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:41])([CH3:42])[CH3:40])[N:22]=[C:23]([NH:24][CH:25]3[CH2:26][CH2:27][N:28]([S:31]([CH3:34])(=[O:33])=[O:32])[CH2:29][CH2:30]3)[C:11]=2[N:10]=1

참가 물질

5

반응물 2

HCID 443297Hydroxyamine hydrochlorideHCID 86664925HCID 86664925, 화합물

생성물 1

HCID 136391029HCID 136391029, 화합물수율 85.1%

시약·촉매·용매 2

HCID 1049Pyridine용매HCID 8857Ethyl Acetate용매

실험 절차

A 100 ml round-bottomed flask equipped with a magnetic stirrer and with a septum having a top-mounted argon intake is charged with 211 mg of 5-(2,6-difluorophenyl)-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazolo[4,3-c]isoquinoline-7-carbaldehyde in 8.5 ml of pyridine, 36 mg of hydroxylamine hydrochloride are added, and the mixture is stirred at RT for 64 h. It is concentrated under RP and the solid obtained is taken up in AcOEt, washed with a 1M aqueous solution of potassium phosphate and then with saturated aqueous NaCl solution, dried over MgSO4, filtered and concentrated under RP. Purification is carried out by flash chromatography on silica gel (20-45 μm), eluting with a mixture of DCM and AcOEt (75/25 by vol.), to give 184 mg of 5-(2,6-difluorophenyl)-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazolo[4,3-c]isoquinoline-7-carbaldehyde oxime (yellow solid). MS (E/I): m/z=630 (M+); 1H NMR: 0.04 (s, 9H); 0.89 (m, 2H); 1.61 (m, 2H); 2.11 (m, 2H); 2.74 (m, 2H); 2.85 (s, 3H); 3.58 (m, 2H); 3.67 (m, 2H); 4.46 (m, 1H); 5.65 (s, 2H); 6.50 (d, J=8.3 Hz, 1H); 7.33 (broad t, J=8.1 Hz, 2H); 7.65 (m, 1H); 7.72 (broad s, 1H); 8.01 (dd, J=8.4, 17 Hz, 1H); 8.27 (s, 1H); 8.35 (d, J=8.4 Hz, 1H); 11.39 (s, 1H).

후처리

  1. customA 100 ml round-bottomed flask equipped with a magnetic stirrer and with a septum
  2. additionare added
  3. concentrationIt is concentrated under RP
  4. customthe solid obtained
  5. washwashed with a 1M aqueous solution of potassium phosphate
  6. dry with materialwith saturated aqueous NaCl solution, dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under RP
  9. customPurification
  10. washeluting with a mixture of DCM and AcOEt (75/25 by vol.)

출처 및 근거

ORD 기록
ord-c3fcecbac92e4492b6b7702501bc0f4a
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08461175B2

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