Triethylamine → tert-butyl {4-[7-benzyloxy-1-(2-phenoxyethyl)-1H-imidazo[4,5-c]quinolin-2-yl]butyl}carbamate

HRID 598279

Reaction equation

HRID 598279 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13](O)=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.C(Cl)(=O)C(C)(C)C.[CH2:30]([O:37][C:38]1[CH:47]=[C:46]2[C:41]([C:42]([NH:49][CH2:50][CH2:51][O:52][C:53]3[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=3)=[C:43]([NH2:48])[CH:44]=[N:45]2)=[CH:40][CH:39]=1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>ClC(Cl)C.CN(C)C1C=CN=CC=1.C(OCC)C>[CH2:30]([O:37][C:38]1[CH:39]=[CH:40][C:41]2[C:42]3[N:49]([CH2:50][CH2:51][O:52][C:53]4[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=4)[C:13]([CH2:12][CH2:11][CH2:10][CH2:9][NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[N:48][C:43]=3[CH:44]=[N:45][C:46]=2[CH:47]=1)[C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 5458485-(((Tert-butoxy)carbonyl)amino)pentanoic acidHCID 670509287-benzyloxy-N4-(2-phenoxyethyl)quinoline-3,4-diamine

Product 1

HCID 86626156tert-butyl {4-[7-benzyloxy-1-(2-phenoxyethyl)-1H-imidazo[4,5-c]quinolin-2-yl]butyl}carbamateYield 82.6%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 3283Diethyl EtherSolventHCID 63651,1-DichloroethaneSolvent

Procedure

Under a nitrogen atmosphere, a solution of 5-(tert-butoxycarbonylamino)valeric acid (1.50 g, 6.91 mmol) in dichloroethane (30 mL) was cooled to −25° C. Triethylamine (2.40 mL, 17.2 mmol) and pivaloyl chloride (0.85 mL, 6.91 mmol) were added, and the reaction was stirred for three hours, during which time the temperature rose to −10° C. 7-Benzyloxy-N4-(2-phenoxyethyl)quinoline-3,4-diamine (0.850 g, 2.20 mmol), prepared as described in Parts A-B of Example 46, was added in one portion followed by a small scoop of 4-dimethylaminopyridine. The reaction was allowed to warm to room temperature and stirred overnight and then heated at reflux for three hours. The reaction solution was washed with saturated sodium bicarbonate, water (2×), and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (eluting with sequentially with 98:2 and 95:5 chloroform:methanol) to yield a solid. The solid was treated with diethyl ether and concentrated under reduced pressure to provide 1.03 g of tert-butyl {4-[7-benzyloxy-1-(2-phenoxyethyl)-1H-imidazo[4,5-c]quinolin-2-yl]butyl}carbamate as a white powder.

Workup

  1. customrose to −10° C
  2. additionwas added in one portion
  3. stirringstirred overnight
  4. temperatureheated
  5. temperatureat reflux for three hours
  6. washThe reaction solution was washed with saturated sodium bicarbonate, water (2×), and brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude product was purified by column chromatography on silica gel (
  11. washeluting with sequentially with 98:2 and 95:5 chloroform
  12. custommethanol) to yield a solid
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ac0122439eb4473bad5de374c851ebf7
Source dataset
uspto-grants-2011_03
Patent number
US07897597B2

Linked notes

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