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

HRID 408775노트

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HRID 408775 반응식
[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]

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

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

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온도
50 °C

실험 절차

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]+.

후처리

  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)

출처 및 근거

ORD 기록
ord-89d84e2fa67c4fb5b0bad5195db08e5d
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759345B2

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