3-Ethynyl-1-methyl-3-pyrrolidinol → 9-(3-Hydroxy-1-methyl-pyrrolidin-3-ylethynyl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amide

HRID 575074노트

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HRID 575074 반응식
Br[C:2]1[CH:3]=[CH:4][C:5]2[O:14][CH2:13][CH2:12][N:11]3[C:7](=[N:8][C:9]([C:15]([NH2:17])=[O:16])=[CH:10]3)[C:6]=2[CH:18]=1.[C:19]([C:21]1([OH:27])[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22]1)#[CH:20]>C(#N)C.C(N(CC)CC)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[OH:27][C:21]1([C:19]#[C:20][C:2]2[CH:3]=[CH:4][C:5]3[O:14][CH2:13][CH2:12][N:11]4[C:7](=[N:8][C:9]([C:15]([NH2:17])=[O:16])=[CH:10]4)[C:6]=3[CH:18]=2)[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22]1

참가 물질

7

반응물 2

HCID 649161603-Ethynyl-1-methyl-3-pyrrolidinolHCID 6831288310-Bromo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide

생성물 1

HCID 717147279-(3-Hydroxy-1-methyl-pyrrolidin-3-ylethynyl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amide수율 10%

시약·촉매·용매 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418476HCID 178418476, 화합물촉매HCID 6342Acetonitrile용매HCID 8471Triethylamine용매

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온도
100 °C

실험 절차

This compound was prepared according to a procedure similar to that described in Procedure E. In a solution of 9-Bromo-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amide (200 mg, 0.64 mmol) in acetonitrile (3 mL) and triethylamine (3 mL) were added, Pd(PPh3)2Cl2 (44 mg, 0.06 mmol), 3-Ethynyl-1-methyl-pyrrolidin-3-ol (160 mg, 1.3 mmol) and CuI (12 mg, 0.06 mmol). Then the solution was bubbled N2 for 5 min and heated by microwave for 1 h at 100° C. under nitrogen. The reaction mixture was filtered and the filtrate was purified by column to afford crude product. The crude product was purified by Prep HPLC to afford the titled compound (22.3 mg, 10%). 1H NMR (DMSO-d6, 400 MHz): δ 8.52 (d, J=2.0 Hz, 1H), 8.18 (s, 1H), 7.79 (s, 1H), 7.56 (s, 1H), 7.32 (d, J=8.8 Hz, 1H), 7.15 (s, 1H), 7.03 (d, J=8.4 Hz, 1H), 4.48 (s, 4H), 2.95 (m, 1H), 2.77 (m, 2H), 2.67 (m, 1H), 2.31 (s, 3H), 2.28 (m, 1H), 2.08 (m, 1H). LCMS=353.1 [M+H]+.

후처리

  1. customThis compound was prepared
  2. customThen the solution was bubbled N2 for 5 min
  3. filtrationThe reaction mixture was filtered
  4. customthe filtrate was purified by column
  5. customto afford crude product
  6. customThe crude product was purified by Prep HPLC

출처 및 근거

ORD 기록
ord-26ea36cfdd2f4ea1a51d2c80e42a1bc2
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09034866B2

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