HCID 86681606、化合物 → (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 571346ノート

反応式

HRID 571346 の反応式
[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]

参加物

5

反応物 2

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

生成物 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-oxide収率 77.9%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒

実験手順

(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]+

後処理

  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)

出典と根拠

ORDレコード
ord-75ac355e2c434a8893b2ddcb818fe750
出典データセット
uspto-grants-2015_05
特許番号
US09024027B2

反応ノート

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