HCID 86681606, 화합물 → (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(1,3-dioxo-3,4-dihydroisoquinolin-2(1H)-yl)acetoxy)ethyl)pyridine 1-oxide

HRID 571346노트

반응식

HRID 571346 반응식
[Cl:1][C:2]1[CH:3]=[N+:4]([O-:44])[CH:5]=[C:6]([Cl:43])[C:7]=1[CH2:8][C@@H:9]([C:28]1[CH:33]=[CH:32][C:31]([O:34][CH:35]([F:37])[F:36])=[C:30]([O:38][CH2:39][CH:40]2[CH2:42][CH2:41]2)[CH:29]=1)[O:10][C:11](=[O:27])[CH2:12][N:13]1[C:21](=[O:22])[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([N+]([O-])=O)[CH:19]=2)[C:14]1=[O:26].O=[C:46]1C2C(=CC=CC=2)CC(=O)N1CC(Cl)=O>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Cl:43][C:6]1[CH:5]=[N+:4]([O-:44])[CH:3]=[C:2]([Cl:1])[C:7]=1[CH2:8][C@@H:9]([C:28]1[CH:33]=[CH:32][C:31]([O:34][CH:35]([F:37])[F:36])=[C:30]([O:38][CH2:39][CH:40]2[CH2:42][CH2:41]2)[CH:29]=1)[O:10][C:11](=[O:27])[CH2:12][N:13]1[C:21](=[O:22])[CH2:46][C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14]1=[O:26]

참가 물질

5

반응물 2

HCID 86681606HCID 86681606, 화합물HCID 866817622-(1,3-dioxo-3,4-dihydroisoquinolin-2(1H)-yl)acetyl chloride

생성물 1

HCID 86681763(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(1,3-dioxo-3,4-dihydroisoquinolin-2(1H)-yl)acetoxy)ethyl)pyridine 1-oxide수율 77.9%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매

실험 절차

(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(5-nitro-1,3-dioxoisoindolin-2-yl)acetoxy)ethyl)pyridine 1-oxide (40 mg, 0.062 mmol) was dissolved in DCM (2 ml), and added with 2-(1,3-dioxo-3,4-dihydroisoquinolin-2(1H)-yl)acetyl chloride (163 mg, 0.686 mmol) and DMAP (84 mg, 0.686 mmol). The reaction was stirred at RT overnight and quenched by addition of HCl. The solution extracted with DCM and washed with NaHCO3 sat. sol., then dried over Na2SO4 and the solvent removed under reduced pressure. The crude was purified by preparative HPLC (Method 2) to yield the titled compound (30.0 mg, 52% yield).). 1H NMR (400 MHz, acetone) ppm 8.19 (s, 2H), 8.09-8.15 (m, 1H), 7.67-7.79 (m, 1H), 7.44-7.61 (m, 2H), 7.15-7.24 (m, 2H), 7.01-7.09 (m, 1H), 6.94 (t, J=75.00 Hz, 1H), 6.01-6.25 (m, 1H), 4.68 (s, 2H), 4.24 (s, 2H), 4.03 (dd, J=6.84, 2.87 Hz, 2H), 3.42-3.60 (m, 1H), 3.20-3.38 (m, 1H), 1.24-1.46 (m, 1H), 0.65 (dd, J=8.16, 1.54 Hz, 2H), 0.43 (d, J=5.73 Hz, 2H); MS/ESI+ 621.3 [MH]+

후처리

  1. customquenched by addition of HCl
  2. extractionThe solution extracted with DCM
  3. washwashed with NaHCO3 sat. sol.
  4. dry with materialdried over Na2SO4
  5. customthe solvent removed under reduced pressure
  6. customThe crude was purified by preparative HPLC (Method 2)

출처 및 근거

ORD 기록
ord-75ac355e2c434a8893b2ddcb818fe750
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09024027B2

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