Chloride → 2-(4-((2-(cyclopentyloxy)-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)methyl)phenyl)acetic acid

HRID 1508791노트

반응식

HRID 1508791 반응식
Cl[C:2]1[CH:7]=[C:6]([O:8][CH:9]2[CH2:13][CH2:12][CH2:11][CH2:10]2)[N:5]=[C:4]2[CH2:14][CH2:15][CH2:16][C:3]=12.CC1(C)C(C)(C)OB([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([CH2:32][C:33]([O:35]C)=[O:34])=[CH:28][CH:27]=2)O1.C([O-])([O-])=O.[Na+].[Na+].[Cl-]>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].O.O1CCOCC1>[CH:9]1([O:8][C:6]2[N:5]=[C:4]3[CH2:14][CH2:15][CH2:16][C:3]3=[C:2]([CH2:25][C:26]3[CH:27]=[CH:28][C:29]([CH2:32][C:33]([OH:35])=[O:34])=[CH:30][CH:31]=3)[CH:7]=2)[CH2:13][CH2:12][CH2:11][CH2:10]1

참가 물질

8

반응물 4

HCID 312ChlorideHCID 10340Sodium CarbonateHCID 674944814-(2-Methoxy-2-oxoethyl)benzylboronic Acid Pinacol EsterHCID 903386264-chloro-2-(cyclopentyloxy)-6,7-dihydro-5H-cyclopenta[b]pyridine

생성물 1

HCID 1180372912-(4-((2-(cyclopentyloxy)-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)methyl)phenyl)acetic acid

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 312751,4-Dioxane용매

실험 절차

A 20-mL sealed tube, with stirrer bar, was charged with 4-chloro-2-(cyclopentyloxy)-6,7-dihydro-5H-cyclopenta[b]pyridine (0.103 g, 0.43 mol), methyl 2-(4-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)phenyl)acetate (0.126 g, 0.43 mmol), Pd(dppf)Cl2 (0.035 g, 0.043 mmol), and powdered Na2CO3 (0.184 g, 1.74 mmol). Dioxane (4 mL) and water (2 mL) were added. The resulting mixture was stirred under Ar at 90° C. for 24 h. until the starting chloride was consumed. After this time, the mixture was cooled to room temperature and the reaction mixture absorbed onto silica (4 g). Purification by chromatography on silica using dichloromethane/methanol (10:0 to 8:2) as eluent to afford 2-(4-((2-(cyclopentyloxy)-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)methyl)phenyl)acetic acid. MW=351.44. MS: ESI+, m/z 352 [M+H]+. This product was dissolved in methanol and treated with 4M HCl/methanol and stirred for 3 days. The reaction was concentrated under reduced pressure. The residue (0.154 g) was treated with minimum saturated sodium bicarbonate then purified by chromatography on silica using hexanes/ethyl acetate (10:0 to 1:1) as eluent to afford the title compound (0.038 g, 24%) as a colorless oil. MW=365.47. 1H NMR (CDCl3, 300 MHz) δ 7.23-7.17 (m, 2H), 7.14-7.08 (m, 2H), 6.22 (s, 1H), 5.35-5.26 (m, 1H), 3.81 (s, 2H), 3.69 (s, 3H), 3.60 (s, 2H), 2.89 (t, J=8.0 Hz, 2H), 2.72 (t, J=7.5 Hz, 2H), 2.06 (quin, J=7.5 Hz, 2H), 1.98-1.88 (m, 2H), 1.85-1.68 (m, 4H), 1.66-1.53 (m, 2H); APCI MS 366 [M+H]+.

후처리

  1. customA 20-mL sealed tube
  2. customwas consumed
  3. customthe reaction mixture absorbed onto silica (4 g)
  4. customPurification by chromatography on silica

출처 및 근거

ORD 기록
ord-82ddf44812ce4d88b8a709a3d1cfdf2b
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09221843B2

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