Hydrochloric Acid → HCID 178501691, compound

HRID 1076421Notes

Reaction equation

HRID 1076421 reaction equation
[NH:1]([C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14])[C@H:2]([C:9]([NH:11]N)=[O:10])[CH2:3][C:4]1[N:8]=[CH:7][NH:6][CH:5]=1.Cl.CCOCC.N(OC(C)(C)C)=O.N[C@H:37]([C:45]([NH:47][C@H:48]([C:56]([NH:58][C@H:59]([C:66]([NH:68][CH2:69][C:70]([O:72][CH3:73])=[O:71])=[O:67])[CH2:60][O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:57])[CH2:49][C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)=[O:46])[CH2:38][CH2:39][CH2:40][NH:41][C:42](=[NH:44])[NH2:43]>CN(C)C=O.C(N(CC)CC)C>[NH:1]([C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14])[C@H:2]([C:9]([NH:11][C@H:37]([C:45]([NH:47][C@H:48]([C:56]([NH:58][C@H:59]([C:66]([NH:68][CH2:69][C:70]([O:72][CH3:73])=[O:71])=[O:67])[CH2:60][O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:57])[CH2:49][C:50]1[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=1)=[O:46])[CH2:38][CH2:39][CH2:40][NH:41][C:42](=[NH:43])[NH2:44])=[O:10])[CH2:3][C:4]1[N:8]=[CH:7][NH:6][CH:5]=1

Participants

8

Reactant 5

HCID 313Hydrochloric Acid2×HCID 3283Diethyl EtherHCID 10906Tert-Butyl nitriteHCID 178501692HCID 178501692, compoundHCID 178514453HCID 178514453, compound

Product 1

HCID 178501691HCID 178501691, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent5×HCID 8471TriethylamineSolvent2×

Procedure

7.6 g of Z-His-NH-NH2 (25 mmols) are suspended in 60 ml of dimethylformamide, 31 ml of hydrogen chloride in ether (2.43 N,. 75.3 mmols) are added at -16°C and the clear yellowish solution thereby obtained is mixed, at -18°C, with 3.2 ml of t-butyl nitrite (95 % strength, 26.5 mmols) in 10 ml of dimethylformamide. After 10 minutes 10.4 ml of triethylamine (75 mmols) in 25 ml of pre-cooled dimethylformamide, and 8.5 g of H-Arg-Phe-Ser(tBu)-Gly-OCH3. 2 HCl (14 mmols) in 50 ml of pre-cooled dimethylformamide are added. The mixture is diluted with 40 ml of dimethylformamide and four portions each of 1.0 ml of triethylamine (a total of 28.7 mmols) are added in intervals of 5 minutes. The mixture is allowed to stand for a further 3 hours at 0°C and for 20 hours at room temperature, the precipitated salts are then filtered off, and the reaction solution is concentrated in vacuo to about three-fourths of its volume. On repeatedly stirring the product into a large amount of ethyl acetate a crude product is obtained which is purified by counter-current distibution in the system methanol-buffer-chloroform-carbon tetrachloride (9:3.5:8:2) through 130 stages (buffer as under 18); rmax = 54; K = 0.7. The pure fractions are combined, evaporated, freed of ammonium acetate in a high vacuum at 40°C, and lyophilised after solution in water.

Workup

  1. customthe clear yellowish solution thereby obtained
  2. additionare added in intervals of 5 minutes
  3. filtrationthe precipitated salts are then filtered off
  4. concentrationthe reaction solution is concentrated in vacuo to about three-fourths of its volume
  5. customis obtained which
  6. customis purified by counter-current distibution in the system methanol-buffer-chloroform-carbon tetrachloride (9:3.5:8:2) through 130 stages (buffer as under 18)
  7. customevaporated
  8. customfreed of ammonium acetate in a high vacuum at 40°C

Sources & evidence

ORD record
ord-cb4b6d9d09264dd6a27aca72c74eb96a
Source dataset
uspto-grants-1976_05
Patent number
US03956260

Reaction notes

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