Dimethylformamide → HCID 178446044, compound

HRID 2083825Notes

Reaction equation

HRID 2083825 reaction equation
[ClH:1].[NH2:2][C@H:3]([C:11]([N:13]1[CH2:24][CH2:23][CH2:22][C@H:14]1[C:15]([NH:17][CH2:18][C:19]([NH2:21])=[O:20])=[O:16])=[O:12])[CH2:4][CH2:5][CH2:6][NH:7][C:8](=[NH:10])[NH2:9].[N+](C1C=CC([O:34][C:35](=O)[C@H:36]([CH2:48][CH:49]([CH3:51])[CH3:50])[NH:37][C:38]([O:40][CH2:41][C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)=[O:39])=CC=1)([O-])=O.CN(C)C=O>C(OCC)C>[ClH:1].[CH2:41]([O:40][C:38]([NH:37][C@H:36]([C:35]([NH:2][C@H:3]([C:11]([N:13]1[CH2:24][CH2:23][CH2:22][C@H:14]1[C:15]([NH:17][CH2:18][C:19]([NH2:21])=[O:20])=[O:16])=[O:12])[CH2:4][CH2:5][CH2:6][NH:7][C:8](=[NH:9])[NH2:10])=[O:34])[CH2:48][CH:49]([CH3:50])[CH3:51])=[O:39])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 97647(S)-4-Nitrophenyl 2-(((benzyloxy)carbonyl)amino)-4-methylpentanoateHCID 178479458HCID 178479458, compound

Product 1

HCID 178446044HCID 178446044, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
50 °C

Procedure

A solution of L-arginyl-L-prolyl-glycinamide hydrochloride (from de-protection of 21.2 g. of Nα -benzyloxycarbonyl-L-arginyl-L-prolyl-glycinamide hydrochloride), 17 g. of Nα -benzyloxycarbonyl-L-leucine p-nitrophenyl ester and 85 ml. of dimethylformamide is allowed to stand at 25° C. for 48 hours, warmed to 50° C. for 10 minutes and let stand for six hours at 25° C. The solution is poured slowly into 800 ml. of stirred dry diethyl ether. The sticky solid is separated by decanting, dissolved in 50 ml. of methanol with warming and the solution poured into 500 ml. of stirred ether. The solid is separated and dried at 40° C. under reduced pressure. It is dissolved in 50 ml. of methanol and 450 ml. of chloroform and chromatographed over a column of 170 g. of silica gel (prepared in 10% methanol in chloroform) and eluted with 10 to 20% methanol in chloroform. The desired fractions, as shown by thin layer chromatography, are combined and evaporated to dryness at 40° C. under reduced pressure and the residue is dissolved in 50 ml. of methanol and 25 ml. of ethyl acetate and the solution is dropped slowly into 350 ml. of stirred dry ether. The solid is separated and dried at 40° C. under reduced pressure to give Nα -benzyloxycarbonyl-L-leucyl-L-arginyl-L-prolyl-glycinamide hydrochloride; 11.6 g.; [α]D23 -51.6° (c 1.0, methanol); ultraviolet in methanol λmax 257 E11 3.24.

Workup

  1. waitlet stand for six hours at 25° C
  2. additionThe solution is poured slowly into 800 ml
  3. customThe sticky solid is separated
  4. customby decanting
  5. dissolutiondissolved in 50 ml
  6. temperatureof methanol with warming
  7. additionthe solution poured into 500 ml
  8. customThe solid is separated
  9. customdried at 40° C. under reduced pressure
  10. dissolutionIt is dissolved in 50 ml
  11. customof chloroform and chromatographed over a column of 170 g
  12. washof silica gel (prepared in 10% methanol in chloroform) and eluted with 10 to 20% methanol in chloroform
  13. customevaporated to dryness at 40° C. under reduced pressure
  14. dissolutionthe residue is dissolved in 50 ml
  15. additionof ethyl acetate and the solution is dropped slowly into 350 ml
  16. customThe solid is separated
  17. customdried at 40° C. under reduced pressure

Sources & evidence

ORD record
ord-ac22d7dfcf21464591bc5d7c37f85a2a
Source dataset
uspto-grants-1978_04
Patent number
US04086219

Reaction notes

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