Diisopropylamine → 4-(cyclohexylamino)-8-[[3-(2-ethenylphenyl)phenyl]methyl]-1-(3-fluorophenyl)-1,3,8-triazaspiro[4.5]dec-3-en-2-one

HRID 1641305

Reaktionsgleichung

Reaktionsgleichung von HRID 1641305
Br[C:2]1[CH:3]=[C:4]([CH:31]=[CH:32][CH:33]=1)[CH2:5][N:6]1[CH2:30][CH2:29][C:9]2([N:13]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=3)[C:12](=[O:21])[N:11]=[C:10]2[NH:22][CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)[CH2:8][CH2:7]1.[CH:34]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1B(O)O)=[CH2:35].P(C1C=C(S(O)(=O)=O)C=CC=1)(C1C=C(S(O)(=O)=O)C=CC=1)C1C=C(S(O)(=O)=O)C=CC=1.C(NC(C)C)(C)C>CC(O)=O.CC(O)=O.[Pd].CN(C=O)C.O>[CH:23]1([NH:22][C:10]2[C:9]3([CH2:29][CH2:30][N:6]([CH2:5][C:4]4[CH:3]=[C:2]([C:37]5[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=5[CH:34]=[CH2:35])[CH:33]=[CH:32][CH:31]=4)[CH2:7][CH2:8]3)[N:13]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=3)[C:12](=[O:21])[N:11]=2)[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1

Komponenten

7

Edukt 4

HCID 7912DiisopropylamineHCID 27735872-Vinylbenzeneboronic acidHCID 3675708Tris(3-sulfophenyl)phosphineHCID 1785179678-[(3-bromophenyl)methyl]-4-(cyclohexylamino)-1-(3-fluorophenyl)-1,3,8-triazaspiro[4.5]dec-3-en-2-one

Produkt 1

HCID 1784359014-(cyclohexylamino)-8-[[3-(2-ethenylphenyl)phenyl]methyl]-1-(3-fluorophenyl)-1,3,8-triazaspiro[4.5]dec-3-en-2-one

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 4144353Palladium (II) acetateKatalysatorHCID 21962138N,N-Dimethylformamide--water (1/1)Lösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a solution of 0.020 g (0.039 mmol) 8-(3-bromobenzyl)-4-(cyclohexylamino)-1-(3-fluorophenyl)-1,3,8-triazaspiro[4.5]dec-3-en-2-one (5-3) in 0.5 mL degassed DMF:H2O (4:1) was added 0.006 g (0.039 mmol) (2-vinylphenyl) boronic acid and 0.003 g (0.006 mmol) 3,3′,3″-Phosphinidynetris (benzene sulfonic acid) and 0.001 g (0.002 mmol) palladium II acetate and 16 μL (0.117 mmol) diisopropylamine. The reaction was heated in the microwave at 100° C. for 10 mins. Purification by preparative HPLC (5-95% CH3CN/H2O over 30 min, 0.05% added TFA, C18 PRO YMC 20×150 mm) afforded 4-(cyclohexylamino)-1-(3-fluorophenyl)-8-[(2′-vinyl-1,1′-biphenyl-3-yl)methyl]-1,3,8-triazaspiro[4.5]dec-3-en-2-one as a white solid. NMR 1H NMR (CD3OD) δ 7.65 (dd, J=6.8 Hz, 2.2 Hz, 1H), 7.43 (dt, J=7.96 Hz, 6.32 Hz, 1H), 7.34 (m, 3H) 7.17 (m, 7H), 6.61 (dd, J=17.49 Hz, 10.99 Hz, 1H), 5.70 (d, J=17.58, 1H), 5.15 (d, J=10.99 Hz, 1H), 3.75 (m, 1H), 3.46 (s, 1H), 2.78 (m, 2H), 2.14 (m, 6H), 1.93 (m, 2H), 1.74 (m, 2H), 1.63 (m, 1H), 1.34 (m, 4H), 1.17 (m, 1H). High resolution mass spec (FT/ICR) calc M+H=537.3024 found 537.3038.

Aufarbeitung

  1. customPurification by preparative HPLC (5-95% CH3CN/H2O over 30 min
  2. addition0.05% added TFA

Quellen und Nachweise

ORD-Eintrag
ord-6dd6b0cb8e604526bc2330704caefdd1
Quelldatensatz
uspto-grants-2012_02
Patentnummer
US08114887B2

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