Diethylene glycol bis(3-aminopropyl) ether → N-(3-(2-(2-(3-Aminopropoxy)ethoxy)ethoxy)propyl)-5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide

HRID 1644154Notes

Reaction equation

HRID 1644154 reaction equation
O[C:2]([CH2:4][CH2:5][CH2:6][CH2:7][C@H:8]1[C@@H:16]2[C@@H:11]([NH:12][C:13]([NH:15]2)=[O:14])[CH2:10][S:9]1)=[O:3].[CH2:17]([NH2:31])[CH2:18][CH2:19][O:20][CH2:21][CH2:22][O:23][CH2:24][CH2:25][O:26][CH2:27][CH2:28][CH2:29][NH2:30].C(N)(N)OOOCCCCCCCCC.[K+].[Br-]>CO.C(N(CC)CC)C.CN(C=O)C>[NH2:30][CH2:29][CH2:28][CH2:27][O:26][CH2:25][CH2:24][O:23][CH2:22][CH2:21][O:20][CH2:19][CH2:18][CH2:17][NH:31][C:2](=[O:3])[CH2:4][CH2:5][CH2:6][CH2:7][C@H:8]1[C@@H:16]2[C@@H:11]([NH:12][C:13]([NH:15]2)=[O:14])[CH2:10][S:9]1

Participants

8

Reactant 4

HCID 20239Diethylene glycol bis(3-aminopropyl) etherHCID 171548Biotin2×HCID 253877Potassium BromideHCID 87146561Trioxatridecanediamine

Product 1

HCID 12068534N-(3-(2-(2-(3-Aminopropoxy)ethoxy)ethoxy)propyl)-5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

Biotin TFP ester (5 g, 12.8 mmol) was added to a dry flask containing 200 mL anhydrous DMF. In another dry flask containing 28 g (128 mmol) 4,7,10-trioxa-1,13-tridecanediamine, 8, was added 4 mL of triethylamine. Both flasks were cooled to 0-5° C. with ice-water baths. The TFP ester of biotin was added dropwise to the tri-oxatridecanediamine solution over the period of 1 h. The reaction was stirred at room temperature for 30 min and the solvent was removed under vacuum. The resulting oil was triturated in 500 mL ether and was stirred for 30 min. The solid was filtered, then dissolved in methanol:ethyl acetate (4:1), and loaded onto a silica column (2.5 cm×35 cm). The column was eluted with the same solvent mixture. Fractions containing product were collected, and solvent was removed under vacuum. The isolated product was dried under vacuum to yield 4.5 g (79%) of, 9, as a colorless solid, mp 104-106° C. 1H NMR (MeOH, ( ): 1.46 (m, 2H), 1.6-1.8 (m, 9H), 2.2 (t, 2H), 2.7 (d, 1H), 2.75-2.9 (m, 3H), 3.2-3.3 (m, 5H), 3.5-3.6 (m, 14H), 4.3 (m, 1H), 4.5 (m, 1H); IR (KBr, cm-1): 3280, 2910, 2850, 1690, 1640, 1110, 940. Analysis calc. for C20H38N4O5S.H2O: C, 51.70; H, 8.68; N, 12.06. Found: C, 51.95; H, 7.98; N, 11.65.

Workup

  1. customthe solvent was removed under vacuum
  2. customThe resulting oil was triturated in 500 mL ether
  3. stirringwas stirred for 30 min
  4. filtrationThe solid was filtered
  5. dissolutiondissolved in methanol:ethyl acetate (4:1)
  6. washThe column was eluted with the same solvent mixture
  7. additionFractions containing product
  8. customwere collected
  9. customsolvent was removed under vacuum
  10. customThe isolated product was dried under vacuum
  11. customto yield 4.5 g (79%) of, 9

Sources & evidence

ORD record
ord-ff2e6ddd96014772b5b8ce4adef9d1a3
Source dataset
uspto-grants-2012_02
Patent number
US08124364B2

Reaction notes

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