Triphenylphosphine → 4-(9-Benzenesulfonyl-3-bromo-6-cyano-9H-dipyrido[2,3-b;4',3'-d]pyrrol-5-yloxy)piperidine-1-carboxylic acid tert-butyl ester

HRID 60321노트

반응식

HRID 60321 반응식
[C:1]1([S:7]([N:10]2[C:14]3[CH:15]=[N:16][C:17]([C:20]#[N:21])=[C:18]([OH:19])[C:13]=3[C:12]3[CH:22]=[C:23]([Br:26])[CH:24]=[N:25][C:11]2=3)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:27]([O:31][C:32]([N:34]1[CH2:39][CH2:38][CH:37](O)[CH2:36][CH2:35]1)=[O:33])([CH3:30])([CH3:29])[CH3:28].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[C:27]([O:31][C:32]([N:34]1[CH2:39][CH2:38][CH:37]([O:19][C:18]2[C:13]3[C:12]4[CH:22]=[C:23]([Br:26])[CH:24]=[N:25][C:11]=4[N:10]([S:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)(=[O:8])=[O:9])[C:14]=3[CH:15]=[N:16][C:17]=2[C:20]#[N:21])[CH2:36][CH2:35]1)=[O:33])([CH3:30])([CH3:28])[CH3:29]

참가 물질

6

반응물 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 582664728-(Benzenesulfonyl)-12-bromo-3-hydroxy-5,8,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaene-4-carbonitrile

생성물 1

HCID 583652284-(9-Benzenesulfonyl-3-bromo-6-cyano-9H-dipyrido[2,3-b;4',3'-d]pyrrol-5-yloxy)piperidine-1-carboxylic acid tert-butyl ester수율 78.1%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
50 °C

실험 절차

A solution of 9-benzenesulfonyl-3-bromo-5-hydroxy-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (15.8 g, 36.8 mmol), 4-hydroxypiperidine-1-carboxylic acid tert-butyl ester (18.5 g, 92.0 mmol) and triphenylphosphine (24.1 g, 92.0 mmol) in anhydrous THF (100 mL) was treated dropwise with diethyl azodicarboxylate (18.1 mL, 92.0 mmol) and the mixture heated to 50° C. for 40 minutes. After this time, the reaction mixture was concentrated in-vacuo and the resultant residue purified by flash chromatography (silica, 2×330 g column, ISCO, 0-10% ethyl acetate in dichloromethane). The resultant product was further purified by trituration with diethyl ether to afford the title compound as an off-white solid (17.6 g, 78%). 1H NMR (300 MHz, CDCl3): 9.57 (s, 1H), 8.76 (d, J=2.3 Hz, 1H), 8.57 (d, J=2.3 Hz, 1H), 8.23-8.22 (m, 2H), 7.64-7.63 (m, 1H), 7.53-7.51 (m, 2H), 5.20-5.20 (m, 1H), 4.07 (d, J=13.6 Hz, 2H), 3.06 (t, J=12.1 Hz, 2H), 2.20-2.19 (m, 2H), 1.85-1.85 (m, 2H), 1.47 (s, 9H).

후처리

  1. concentrationAfter this time, the reaction mixture was concentrated in-vacuo
  2. customthe resultant residue purified by flash chromatography (silica, 2×330 g column, ISCO, 0-10% ethyl acetate in dichloromethane)
  3. customThe resultant product was further purified by trituration with diethyl ether

출처 및 근거

ORD 기록
ord-954806a2bbf1414d97fdb7f8c338bba5
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09440976B2

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