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4-(1-Piperidylmethyl)phenylboronic Acid → 5-(2-Methoxyethoxy)-3-(4-piperidin-1-ylmethylphenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

HRID 1505976
ノート
印刷プレビュー

反応式

HRID 1505976 の反応式
Br[C:2]1[CH:21]=[N:20][C:5]2[NH:6][C:7]3[CH:12]=[N:11][C:10]([C:13]#[N:14])=[C:9]([O:15][CH2:16][CH2:17][O:18][CH3:19])[C:8]=3[C:4]=2[CH:3]=1.[N:22]1([CH2:28][C:29]2[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=2)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1>C(=O)([O-])[O-].[Na+].[Na+].C(#N)C.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:19][O:18][CH2:17][CH2:16][O:15][C:9]1[C:8]2[C:4]3[CH:3]=[C:2]([C:32]4[CH:31]=[CH:30][C:29]([CH2:28][N:22]5[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]5)=[CH:34][CH:33]=4)[CH:21]=[N:20][C:5]=3[NH:6][C:7]=2[CH:12]=[N:11][C:10]=1[C:13]#[N:14]
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 2

HCID 230053434-(1-Piperidylmethyl)phenylboronic AcidHCID 670276773-bromo-5-(2-methoxy-ethoxy)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

生成物 1

HCID 582665065-(2-Methoxyethoxy)-3-(4-piperidin-1-ylmethylphenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile収率 32%

試薬・触媒・溶媒 4

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)
触媒
HCID 962Water溶媒
HCID 6342Acetonitrile溶媒
HCID 10340Sodium Carbonate溶媒

反応条件

温度
140 °C

実験手順

A degassed mixture of 3-bromo-5-(2-methoxy-ethoxy)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (50 mg, 0.10 mmol), 4-piperidin-1-ylmethylphenyl boronic acid (31 mg, 0.14 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (9 mg, 0.012 mmol) in 2N aqueous sodium carbonate solution (0.42 mL) and acetonitrile (0.53 mL) were heated under microwave irradiation at 140° C. for 30 minutes. The reaction mixture was diluted with water (2 mL) and extracted with 10% MeOH in DCM. The combined organic phase was concentrated in vacuo and the resultant residue was purified by flash chromatography (silica, 500 mg column, Si-SPE, 0-20% methanol in DCM). The resultant residue was dissolved in a solution of 0.15M potassium hydroxide in methanol (7 mL) and stirred for 45 minutes. 1N Potassium dihydrogen phosphate (1 mL) was added then the mixture concentrated in vacuo. The resultant residue was diluted with water and the pH adjusted to 7 by the addition of 1N potassium dihydrogen phosphate. The aqueous phase was extracted with DCM (3×10 mL) and 20% ethanol in DCM (10 mL), the combined organic phase was dried over magnesium sulfate and concentrated in vacuo. The resultant residue was purified by flash chromatography (silica, 500 mg column, Si-SPE, 2-4% methanol in DCM) and trituration with acetonitrile to afford the title compound as a brown solid (14 mg, 32%). 1H NMR (CDCl3, 300 MHz): 9.91 (s, 1H), 9.09 (d, J=2.2 Hz, 1H), 8.93 (d, J=2.2 Hz, 1H), 8.80 (s, 1H), 7.67 (d, J=8.1 Hz, 2H), 7.49 (d, J=8.0 Hz, 2H), 4.75-4.69 (m, 2H), 3.95-3.89 (m, 2H), 3.58 (s, 2H), 3.47 (s, 3H), 2.51-2.37 (m, 4H), 1.68-1.54 (m, 4H), 1.52-1.41 (m, 2H). LCMS (Method A): RT=6.27 min, M+H+=442.

後処理

  1. extractionextracted with 10% MeOH in DCM
  2. concentrationThe combined organic phase was concentrated in vacuo
  3. customthe resultant residue was purified by flash chromatography (silica, 500 mg column, Si-SPE, 0-20% methanol in DCM)
  4. dissolutionThe resultant residue was dissolved in a solution of 0.15M potassium hydroxide in methanol (7 mL)
  5. addition1N Potassium dihydrogen phosphate (1 mL) was added
  6. concentrationthe mixture concentrated in vacuo
  7. additionThe resultant residue was diluted with water
  8. additionthe pH adjusted to 7 by the addition of 1N potassium dihydrogen phosphate
  9. extractionThe aqueous phase was extracted with DCM (3×10 mL) and 20% ethanol in DCM (10 mL)
  10. dry with materialthe combined organic phase was dried over magnesium sulfate
  11. concentrationconcentrated in vacuo
  12. customThe resultant residue was purified by flash chromatography (silica, 500 mg column, Si-SPE, 2-4% methanol in DCM) and trituration with acetonitrile

出典と根拠

ORDレコード
ord-8a2493cbe9d54898a46f1eda255dd0fe
出典データセット
uspto-grants-2015_12
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09216980B2

反応ノート

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