Diisopropylethylamine → (Z)-(2R)-3-(((((14E,16E,18E,20E)-15,19-dimethyl-4,7,10,13-tetraoxo-21-(2,6,6-trimethylcyclohex-1-en-1-yl)-3,6,9,12-tetraazahenicosa-14,16,18,20-tetraen-1-yl)oxy)(hydroxy)phosphoryl)oxy)-propane-1,2-diyl dioleate

HRID 1055180Notes

Reaction equation

HRID 1055180 reaction equation
[C:1]([O:20][CH2:21][C@@H:22]([O:44][C:45](=[O:63])[CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52]/[CH:53]=[CH:54]\[CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH3:62])[CH2:23][O:24][P:25]([O:28][CH2:29][CH2:30][NH:31][C:32](=[O:43])[CH2:33][NH:34][C:35](=[O:42])[CH2:36][NH:37][C:38](=[O:41])[CH2:39][NH2:40])([OH:27])=[O:26])(=[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].[CH3:64][C:65]1[CH2:70][CH2:69][CH2:68][C:67]([CH3:72])([CH3:71])[C:66]=1/[CH:73]=[CH:74]/[C:75](/[CH3:85])=[CH:76]/[CH:77]=[CH:78]/[C:79](/[CH3:84])=[CH:80]/[C:81](O)=[O:82].F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[Al]>CN(C)C=O.ClCCl.O>[C:1]([O:20][CH2:21][C@@H:22]([O:44][C:45](=[O:63])[CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52]/[CH:53]=[CH:54]\[CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH3:62])[CH2:23][O:24][P:25]([O:28][CH2:29][CH2:30][NH:31][C:32](=[O:43])[CH2:33][NH:34][C:35](=[O:42])[CH2:36][NH:37][C:38](=[O:41])[CH2:39][NH:40][C:81](=[O:82])/[CH:80]=[C:79](\[CH3:84])/[CH:78]=[CH:77]/[CH:76]=[C:75](\[CH3:85])/[CH:74]=[CH:73]/[C:66]1[C:67]([CH3:71])([CH3:72])[CH2:68][CH2:69][CH2:70][C:65]=1[CH3:64])([OH:27])=[O:26])(=[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]

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 444795Retinoic AcidHCID 5359268AluminumHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86688872HCID 86688872, compound

Product 1

HCID 89373008(Z)-(2R)-3-(((((14E,16E,18E,20E)-15,19-dimethyl-4,7,10,13-tetraoxo-21-(2,6,6-trimethylcyclohex-1-en-1-yl)-3,6,9,12-tetraazahenicosa-14,16,18,20-tetraen-1-yl)oxy)(hydroxy)phosphoryl)oxy)-propane-1,2-diyl dioleateYield 70.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

(Z)-(2R)-3-(((2-(2-(2-(2-aminoacetamido)acetamido)acetamido)ethoxy)(hydroxy)phosphoryl)oxy)propane-1,2-diyl dioleate (765 mg, 0.836 mmol), retinoic acid (301 mg, 1.00 mmol), and N,N,N′,N′-Tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (413 mg, 1.09 mmol) were suspended in N,N-Dimethylformamide (5 mL). N,N-Diisopropylethylamine (437 uL, 2.51 mmol) was added and the reaction vessel was flushed with argon gas. Added chloroform (5 mL) to aid in the solvation of materials. Reaction was allowed to stir for ˜4 hours at room temperature in a round bottom flask covered with aluminum foil. Partitioned material between H2O (100 mL) and dichloromethane (100 mL). Extracted with dichloromethane (3×100 mL), dried with sodium sulfate, filtered and concentrated. Material was then purified via silica gel chromatography using a dichloromethane/methanol gradient to yield (Z)-(2R)-3-(((((14E,16E,18E,20E)-15,19-dimethyl-4,7,10,13-tetraoxo-21-(2,6,6-trimethylcyclohex-1-en-1-yl)-3,6,9,12-tetraazahenicosa-14,16,18,20-tetraen-1-yl)oxy)(hydroxy)phosphoryl)oxy)propane-1,2-diyl dioleate as an orange oil (704 mg, 70%). Verified product by LCMS & NMR. 1H NMR (400 MHz), δH: 6.90 (t, 1H), 6.21 (q, 2H), 6.08-6.12 (d, 2H), 5.83 (s, 1H), 5.31 (s, 4H), 5.30 (s, 2H), 4.37 (d, 1H), 4.15 (m, 1H), 3.91 (m, 8H), 3.59 (m, 2H), 3.29 (m, 2H), 3.01 (m, 2H), 2.28 (m, 6H), 1.95-1.98 (m, 12H), 1.44 (s, 3H), 1.5-1.6 (m, 2H), 1.44 (m, 6H), 1.24 (m, ˜48H), 1.00 (s, 6H), 0.86 (t, 3H). MS: m/z 1198.42 (M+Hf).

Workup

  1. customthe reaction vessel was flushed with argon gas
  2. customReaction
  3. extractionExtracted with dichloromethane (3×100 mL)
  4. dry with materialdried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customMaterial was then purified via silica gel chromatography

Sources & evidence

ORD record
ord-3aa0b90aae2441e8b112ddd7a04eaa55
Source dataset
uspto-grants-2016_07
Patent number
US09393315B2

Reaction notes

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