Diisopropylethylamine → (Z)-(2R)-3-(((2-(5-(((2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraen-1-yl)oxy)-5-oxopentanamido)ethoxy)(hydroxy)phosphoryl)oxy)propane-1,2-diyl dioleate

HRID 1055177ノート

反応式

HRID 1055177 の反応式
[C:1]([O:20][CH2:21][C@H:22]([CH2:43][O:44][P:45]([O:48][CH2:49][CH2:50][NH2:51])([OH:47])=[O:46])[O:23][C:24](=[O:42])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]/[CH:32]=[CH:33]\[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.[CH3:76]/[C:77](/[CH:89]=[CH:90]/[CH:91]=[C:92](\[CH3:104])/[CH:93]=[CH:94]/[C:95]1[C:100]([CH3:102])([CH3:101])[CH2:99][CH2:98][CH2:97][C:96]=1[CH3:103])=[CH:78]\[CH2:79][O:80][C:81](=[O:88])[CH2:82][CH2:83][CH2:84][C:85](O)=[O:86].C(N(CC)C(C)C)(C)C>C(Cl)(Cl)Cl.CN(C=O)C>[C:1]([O:20][CH2:21][C@@H:22]([O:23][C:24](=[O:42])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]/[CH:32]=[CH:33]\[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41])[CH2:43][O:44][P:45]([O:48][CH2:49][CH2:50][NH:51][C:85](=[O:86])[CH2:84][CH2:83][CH2:82][C:81]([O:80][CH2:79]/[CH:78]=[C:77](\[CH3:76])/[CH:89]=[CH:90]/[CH:91]=[C:92](\[CH3:104])/[CH:93]=[CH:94]/[C:95]1[C:100]([CH3:101])([CH3:102])[CH2:99][CH2:98][CH2:97][C:96]=1[CH3:103])=[O:88])([OH:47])=[O:46])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 95467571,2-Dioleoyl-sn-glycero-3-phosphoethanolamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 866757085-(((2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraen-1-yl)oxy)-5-oxopentanoic acid

生成物 1

HCID 86675709(Z)-(2R)-3-(((2-(5-(((2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraen-1-yl)oxy)-5-oxopentanamido)ethoxy)(hydroxy)phosphoryl)oxy)propane-1,2-diyl dioleate収率 61%

試薬・触媒・溶媒 1

HCID 21754633chloroform N,N-dimethylformamide溶媒

実験手順

1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (500 mg, 0.672 mmol), N,N,N′,N′-Tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (306.5 mg, 0.806 mmol) and 5-(((2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraen-1-yl)oxy)-5-oxopentanoic acid (269 mg, 0.672 mmol) was dissolved in chloroform/DMF (10 mL, 1:1 mixture) in an amber-colored vial flushed with argon and N,N-Diisopropylethylamine (300 uL, 1.68 mmol) was added. Reaction mixture was allowed to stir overnight at room temperature. The reaction mixture was concentrated and then purified by silica gel chromatography using a dichloromethane/methanol gradient. The fractions were pooled and concentrated to yield yellowish oil (460 mg, 61%). Verified product by NMR. 1H NMR (400 MHz), δH: 8.6 (d, 1H), 8.27 (d, 1H), 6.57-6.61 (dd, 1H), 6.08-6.25 (m, 4H), 5.57 (t, 1H), 5.30-5.34 (m, 4H), 5.18 (m, 1H), 4.68-4.70 (d, 2H), 4.28-4.35 (m, 1H), 4.05-4.15 (m, 1H), 3.81-3.97 (m, 4H), 3.52-3.62 (m, 1H), 3.35-3.45 (m, 2H), 2.95-3.05 (m, 1H), 2.33-2.35 (t, 3H), 2.2-2.3 (m, 7H), 1.9-2.05 (m, 17H), 1.85 (s, 3H), 1.69 (s, 3H), 1.5-1.65 (m, 6H), 1.4-1.5 (m, 2H), 1.18-1.38 (m, ˜40H), 1.01 (s, 3H), 0.84-0.88 (m, 12H).

後処理

  1. additionwas added
  2. customReaction mixture
  3. concentrationThe reaction mixture was concentrated
  4. custompurified by silica gel chromatography
  5. concentrationconcentrated

出典と根拠

ORDレコード
ord-1d64348ace454faeafbe020c3c5ddfde
出典データセット
uspto-grants-2016_07
特許番号
US09393315B2

反応ノート

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