Sodium Bicarbonate → HCID 178451672、化合物

HRID 625560ノート

反応式

HRID 625560 の反応式
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[CH:11][C:12]3[N:16]=[C:15]([C@@H:17]4[CH2:21][CH2:20][CH2:19][N:18]4[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[NH:14][C:13]=3[CH:29]=2)O1.Br[C:32]1[CH:41]=[CH:40][C:39]2[C:34](=[CH:35][CH:36]=[C:37](Br)[CH:38]=2)[CH:33]=1.[C:43]([O-:46])(O)=[O:44].[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:25]([O:24][C:22]([N:18]1[CH2:19][CH2:20][CH2:21][CH:17]1[C:15]1[NH:14][C:13]2[CH:29]=[C:9]([C:32]3[CH:33]=[C:34]4[C:39](=[CH:40][CH:41]=3)[CH:38]=[C:37]([C:9]3[CH:10]=[CH:11][C:12]5[NH:16][C:15]([CH:17]6[CH2:21][CH2:20][CH2:19][N:18]6[C:43]([O:46][C:25]([CH3:26])([CH3:27])[CH3:28])=[O:44])=[N:14][C:13]=5[CH:29]=3)[CH:36]=[CH:35]4)[CH:10]=[CH:11][C:12]=2[N:16]=1)=[O:23])([CH3:26])([CH3:27])[CH3:28]

参加物

7

反応物 3

HCID 516892Sodium BicarbonateHCID 6405912,6-DibromonaphthaleneHCID 56605316HCID 56605316、化合物

生成物 1

HCID 178451672HCID 178451672、化合物収率 55.5%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
100 °C

実験手順

To a mixture of (S)-tert-butyl 2-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-2-yl)pyrrolidine-1-carboxylate (1.29 g, 33.1 mmol) and 2,6-dibromonaphthalene (446 mg, 1.56 mmol) in 1,2-dimethoxyethane (20 mL) and water (6 mL) was added NaHCO3 (787 mg, 9.36 mmol). The reaction mixture was degassed in vacuo for 10 minutes and was flushed with nitrogen. The catalyst Pd(Ph3P)4 (90 mg, 0.078 mmol) was added and the flask was capped and heated with an oil bath at 100° C. for 16 hours. The volatile component was removed in vacuo. The residue was partitioned between CH2Cl2 and water and the layers were separated. The aqueous phase was extracted several times with CH2Cl2 and the combined organic phases were dried (brine, Na2SO4), filtered and concentrated in vacuo. The resulting material was purified with flash chromatography (sample was dry loaded on silica gel and eluted with 0-70% ethyl acetate/CH2Cl2) to afford tert-butyl 2-(5-(6-(2-(1-(tert-butoxycarbonyl)-2-pyrrolidinyl)-1H-benzimidazol-6-yl)-2-naphthyl)-1H-benzimidazol-2-yl)-1-pyrrolidinecarboxylate (605 mg) as yellow solid. LC-MS retention time 1.46 min; calcd. for C42H46N6O4: 698.36. found m/z 699.26 [M+H]+. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters Sunfire 5u C18 4.6×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 4 mL/min, a gradient of 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B, a gradient time of 3 min, a hold time of 1 min and an analysis time of 4 min where Solvent A was 10% acetonitrile/90% water/0.1% TFA and Solvent B was 90% acetonitrile/10% water/0.1% TFA 1H NMR (500 MHz, MeOD) δ ppm 8.28 (br s, 2H), 8.13 (t, J=8.7 Hz, 4H), 8.05 (t, J=8.4 Hz, 2H), 7.92 (dd, J=14.8, 8.7 Hz, 4H), 5.20-5.36 (m, 2H), 3.70-3.84 (m, 2H), 3.57-3.70 (m, 2H), 2.54-2.70 (m, 2H), 2.18-2.28 (m, 2H), 2.14 (quin, J=6.9 Hz, 4H), 1.50 (s, 9H), 1.23 (s, 9H).

後処理

  1. customThe reaction mixture was degassed in vacuo for 10 minutes
  2. customwas flushed with nitrogen
  3. customthe flask was capped
  4. customThe volatile component was removed in vacuo
  5. customThe residue was partitioned between CH2Cl2 and water
  6. customthe layers were separated
  7. extractionThe aqueous phase was extracted several times with CH2Cl2
  8. dry with materialthe combined organic phases were dried (brine, Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe resulting material was purified with flash chromatography (sample was dry loaded on silica gel and eluted with 0-70% ethyl acetate/CH2Cl2)

出典と根拠

ORDレコード
ord-b2b853dfbb154f499970c1ce78aedd86
出典データセット
uspto-grants-2016_04
特許番号
US09303007B2

反応ノート

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