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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 1770947
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HRID 1770947 반응식
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
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참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

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

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온도
130 °C

실험 절차

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, 1H), 7.49 (m, 2H), 7.39 (m, 3H), 6.80 (d, 1H), 6.61 (br. s, 1H), 3.66 (m, 2H), 3.48 (m, 1H), 3.40 (td, 1H), 3.22 (d, 1H), 3.08 (d, 1H), 2.19 (s, m 3H), 1.72 (td, 1H), 1.22 (m, 3H); MS (ES+) m/z 380 [M+H]+.

후처리

  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

출처 및 근거

ORD 기록
ord-dc6420c28f194eddbcb386329c6cdfde
출처 데이터셋
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09248129B2

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