Acetic Acid → HCID 57512042, compound

HRID 971331Notes

Reaction equation

HRID 971331 reaction equation
[C:1]([OH:4])(=O)[CH3:2].Cl.Cl.[NH2:7][C@@H:8]([CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH3:35])[CH:24]=1)[C@H:9]([OH:21])[CH2:10][NH:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH2:19][CH3:20])[CH:14]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[CH2:19]([C:15]1[CH:14]=[C:13]([CH:18]=[CH:17][CH:16]=1)[CH2:12][NH:11][CH2:10][C@@H:9]([OH:21])[C@@H:8]([NH:7][C:1](=[O:4])[CH3:2])[CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH3:35])[CH:24]=1)[CH3:20]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 69316765HCID 69316765, compound

Product 1

HCID 57512042HCID 57512042, compoundYield 22.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of acetic acid (15 pg, 0.2 mmol), amine 92 (100 mg, 0.2 mmol), and HATU (80 mg, 0.2 mmol) in methylene chloride (3 mL) was added N,N-diisopropylethylamine (130 μL, 0.7 mmol). The reaction mixture was stirred at room temperature for 18 h. The reaction mixture was partitioned between methylene chloride and water. The organic layer was washed with water, dried (sodium sulfate), filtered, and concentrated under reduced pressure to afford a crude oil. Purification by flash column chromatography (silica, gradient 95:5 to 90:10 methylene chloride/methanol) provided N-{(1S,2R)-3-[(3-ethylbenzyl)amino]-1-[3-(hexyloxy)benzyl]-2-hydroxypropyl}acetamide 93B (20 mg): mp 102–105° C.; IR (KBr) 3304, 2929, 1637, 1603, 1550 cm 1; 1H NMR (500 MHz, CD3OD)δ 7.26–7.11 (m, 5H), 6.75–6.70 (m, 3H), 4.03–3.60 (m, 6H), 3.10–3.05 (m, 1H), 2.80–2.55 (m, 5H), 1.78–1.72 (m, 2H), 1.78 (s, 3H), 1.46–1.44 (m, 2H), 1.36–1.33 (m, 4H), 1.24–1.21 (m, 3H), 0.93–0.91 (m, 3H); ESI MS m/z 441 [M+H]+.

Workup

  1. customThe reaction mixture was partitioned between methylene chloride and water
  2. washThe organic layer was washed with water
  3. dry with materialdried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto afford a crude oil
  7. customPurification by flash column chromatography (silica, gradient 95:5 to 90:10 methylene chloride/methanol)

Sources & evidence

ORD record
ord-4506fc0aba504afabaa70dc9ecd4c341
Source dataset
uspto-grants-2007_12
Patent number
US07312360B2

Reaction notes

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