Diethylamine → Atreleuton

HRID 1720435

반응식

HRID 1720435 반응식
I[C:2]1[S:3][C:4]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)=[CH:5][CH:6]=1.[OH:15][N:16]([C@@H:20]([C:22]#[CH:23])[CH3:21])[C:17]([NH2:19])=[O:18].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(NCC)C>CN(C=O)C.CC#N.CC#N.Cl[Pd]Cl.[Cu]I>[F:14][C:11]1[CH:12]=[CH:13][C:8]([CH2:7][C:4]2[S:3][C:2]([C:23]#[C:22][C@H:20]([N:16]([OH:15])[C:17]([NH2:19])=[O:18])[CH3:21])=[CH:6][CH:5]=2)=[CH:9][CH:10]=1

참가 물질

8

반응물 4

HCID 8021DiethylamineHCID 11776TriphenylphosphineHCID 10558641(R)-N-hydroxy-N-(3-butyn-2-yl)ureaHCID 106154672-(4-Fluorobenzyl)-5-iodothiophene

생성물 1

HCID 3086671Atreleuton수율 18%

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 6093782Bis(acetonitrile)dichloropalladium촉매HCID 6228Dimethylformamide용매

실험 절차

To a solution of 2-iodo-5-(4-fluorophenylmethyl)thiophene (5.30 g, 16.6 mmol), prepared as in step 2, in anhydrous DMF (5.0 mL) was added (R)-N-hydroxy-N-(3-butyn-2-yl)urea (2.12 g, 16.6 mmol), triphenylphosphine (84 mg, 0.32 mmol), bis(acetonitrile)palladium(II) chloride (40 mg, 0.16 mmol), copper (I) iodide (16 rag, 0.08 mmol), and diethylamine (5.6 ml). The mixture was stirred under nitrogen at ambient temperature for 22 hours and concentrated in vacuo at 32° C. The residue was subjected to chromatography on silica eluting with 2-7% MeOH in CH2Cl2, crystallization from ethyl acetate-hexane and trituration in CH2Cl2 to afford (R)-N-{3-[5-(4-fluorophenylmethyl)thien-2-yl]-1-methyl-2-propynyl}-N-hydroxyurea as a cream-colored solid 0.94 g (18%). m.p. 135°-136° C.(dec). 1H NMR (DMSO-d6, 300 MHz) δ1.32 (d, J=6.0 Hz, 3H), 4.11 (s, 2H), 5.10 (q, J=6.0Hz, 1H), 6.54 (s, 2H), 6.81 (d, J=3.0Hz, 1H), 7.08 (d, J=3.0Hz, 1H), 7.10-7.18 (m, 2H), 7.25-7.32 (m, 2H), 9.33 (s, 1H). MS (DCI/NH3) m/e 319 (M+H)+. [a]D23° =+47.8° (C=1, MeOH). Anal calcd for C16H15FN2O2S: C, 60.36; H, 4.75; N, 8.80. Found: C, 60.31; H, 4.79; N, 8.50.

후처리

  1. concentrationconcentrated in vacuo at 32° C
  2. customThe residue was subjected to chromatography on silica eluting with 2-7% MeOH in CH2Cl2, crystallization from ethyl acetate-hexane and trituration in CH2Cl2

출처 및 근거

ORD 기록
ord-b542e964429c4fb68f9b84c4a70fad81
출처 데이터셋
uspto-grants-1996_04
특허 번호
US05506261

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