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Bromobenzene → 1-[6-Chloro-1-(2-methoxy-ethoxymethyl)-5-phenylamino-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester

HRID 1521447
ノート
印刷プレビュー

反応式

HRID 1521447 の反応式
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]([C:11]2[N:15]([CH2:16][O:17][CH2:18][CH2:19][O:20][CH3:21])[C:14]3[CH:22]=[C:23]([Cl:27])[C:24]([NH2:26])=[CH:25][C:13]=3[N:12]=2)[CH:10]=1)=[O:5])[CH3:2].N[C:29]1[C:45](Cl)=[CH:44][C:32]2NC(N3C=C(C(O)=O)C=N3)=N[C:31]=2[CH:30]=1.BrC1C=CC=CC=1.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].CC(P(C(C)(C)C)[C-]1C=CC=C1)(C)C.C1C=CC([C-]2C(C3C=CC=CC=3)=C(C3C=CC=CC=3)C(C3C=CC=CC=3)=C2C2C=CC=CC=2)=CC=1.[Fe+2]>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]([C:11]2[N:15]([CH2:16][O:17][CH2:18][CH2:19][O:20][CH3:21])[C:14]3[CH:22]=[C:23]([Cl:27])[C:24]([NH:26][C:29]4[CH:45]=[CH:44][CH:32]=[CH:31][CH:30]=4)=[CH:25][C:13]=3[N:12]=2)[CH:10]=1)=[O:5])[CH3:2]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 7961BromobenzeneHCID 23676156Sodium t-butoxideHCID 444790641-(5-Amino-6-chloro-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acidHCID 669373191-[5-Amino-6-chloro-1-(2-methoxy-ethoxymethyl)-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester

生成物 1

HCID 669374571-[6-Chloro-1-(2-methoxy-ethoxymethyl)-5-phenylamino-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester
収率 6%

試薬・触媒・溶媒 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium触媒HCID 129828017Ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane;iron(2+);(2,3,4,5-tetraphenylcyclopenta-1,4-dien-1-yl)benzene触媒

反応条件

温度
50 °C

実験手順

An oven-dried flask was charged with 1-[5-amino-6-chloro-1-(2-methoxy-ethoxymethyl)-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester (Intermediate from Example 41, product from Step A) (0.100 g, 0.254 mmol), bromobenzene (43.8 mg, 0.279 mmol), Pd(dba)2 (1.50 mg, 2.50 μmol), Q-Phos (3.60 mg, 5.10 μmol), and sodium tert-butoxide (36.6 mg, 0.381 mmol). The flask was purged with N2. Dry toluene (0.5 mL) was added and the slurry was briefly sonicated. The reaction mixture was heated at 50° C. for 18 h. The reaction mixture was then diluted with dichloromethane and filtered through a pad of Celite®. The filter cake was rinsed with EtOAc and the filtrate was concentrated under reduced pressure. The residue was purified (FCC) (10-45% EtOAc/hexanes) to yield the titled compound (7.1 mg, 6% yield), which was used in the next step without further purification. MS (ESI/CI): mass calcd. for C23H24ClN5O4, 469.2; m/z found, 470.1 [M+H]+.

後処理

  1. customThe flask was purged with N2
  2. additionDry toluene (0.5 mL) was added
  3. customthe slurry was briefly sonicated
  4. additionThe reaction mixture was then diluted with dichloromethane
  5. filtrationfiltered through a pad of Celite®
  6. washThe filter cake was rinsed with EtOAc
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe residue was purified (FCC) (10-45% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-606669dcb6f4465988bbf887c2e190d0
出典データセット
uspto-grants-2015_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09073923B2

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート