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Potassium Carbonate → 6'-(3-Chlorophenyl)-5-methyl-2'',3'',5'',6''-tetrahydro-3'H-dispiro[imidazole-2,1'-indene-2',4''-pyran]-4-amine

HRID 539338
ノート
印刷プレビュー

反応式

HRID 539338 の反応式
Br[C:2]1[CH:15]=[C:14]2[C:5]([CH2:6][C:7]3([C:13]42[N:19]=[C:18]([NH2:20])[C:17]([CH3:21])=[N:16]4)[CH2:12][CH2:11][O:10][CH2:9][CH2:8]3)=[CH:4][CH:3]=1.[Cl:22][C:23]1[CH:24]=[C:25](B(O)O)[CH:26]=[CH:27][CH:28]=1.C([O-])([O-])=O.[K+].[K+].O1CCOCC1>[Cl-].[Na+].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]>[Cl:22][C:23]1[CH:28]=[C:27]([C:2]2[CH:15]=[C:14]3[C:5]([CH2:6][C:7]4([C:13]53[N:19]=[C:18]([NH2:20])[C:17]([CH3:21])=[N:16]5)[CH2:8][CH2:9][O:10][CH2:11][CH2:12]4)=[CH:4][CH:3]=2)[CH:26]=[CH:25][CH:24]=1
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 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 2734323(3-Chlorophenyl)boronic acidHCID 573858806'-Bromo-5-methyl-2'',3'',5'',6''-tetrahydro-3'H-dispiro[imidazole-2,1'-indene-2',4''-pyran]-4-amine

生成物 1

HCID 679793616'-(3-Chlorophenyl)-5-methyl-2'',3'',5'',6''-tetrahydro-3'H-dispiro[imidazole-2,1'-indene-2',4''-pyran]-4-amine収率 44%

試薬・触媒・溶媒 2

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 57417360Sodium chloride; water溶媒

反応条件

温度
130 °C

実験手順

A mixture of 6′-bromo-5-methyl-2″,3″,5″,6″-tetrahydro-3′H-dispiro[imidazole-2,1′-indene-2′,4″-pyran]-4-amine (Example 25, 75 mg, 0.22 mmol), 3-chlorophenylboronic acid (40.4 mg, 0.26 mmol), [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) chloride (8.86 mg, 10.77 μmol), 2 M aq. K2CO3 (0.215 mL, 0.43 mmol) and 1,4-dioxane (2 mL) were mixed in a vial and heated in a microwave reactor at 130° C. for 15 min. When cooled to r.t., the mixture was diluted with brine (3 mL) and extracted with DCM (3×3 mL). The combined organics were concentrated and the resulting residue was purified by preparative chromatography. The fractions containing the title compound were pooled, the solvent removed in vacuo, and the resulting aqueous residue was extracted with DCM (3×3 mL). The combined organics were passed through a phase separator and concentrated. The resulting residue was taken up in MeOH (2 mL) and dried in a vacuum oven at 40° C. over a weekend to give 36 mg (44% yield) of the title compound; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.55 (t, 1 H), 7.49 (m, 2 H), 7.39 (m, 3 H), 6.80 (d, 1 H), 6.61 (br. s, 1 H), 3.66 (m, 2 H), 3.48 (m, 1 H), 3.40 (td, 1 H), 3.22 (d, 1 H), 3.08 (d, 1 H), 2.19 (s, 3 H), 1.72 (td, 1 H), 1.22 (m, 3 H); MS (ES+) m/z 380 [M+H]+.

後処理

  1. additionwere mixed in a vial and
  2. temperatureWhen cooled to r.t.
  3. extractionextracted with DCM (3×3 mL)
  4. concentrationThe combined organics were concentrated
  5. customthe resulting residue was purified by preparative chromatography
  6. additionThe fractions containing the title compound
  7. customthe solvent removed in vacuo
  8. extractionthe resulting aqueous residue was extracted with DCM (3×3 mL)
  9. concentrationconcentrated
  10. customdried in a vacuum oven at 40° C. over a weekend

出典と根拠

ORDレコード
ord-ec44c22155254085beaad8ead3392739
出典データセット
uspto-grants-2014_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08865911B2

反応ノート

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