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 60321ノート

反応式

HRID 60321 の反応式
[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]

参加物

6

反応物 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

生成物 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 ester収率 78.1%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
50 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-954806a2bbf1414d97fdb7f8c338bba5
出典データセット
uspto-grants-2016_09
特許番号
US09440976B2

反応ノート

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