Hydrochloric Acid → HCID 178445957, compound

HRID 1155459Notes

Reaction equation

HRID 1155459 reaction equation
[NH:1]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C@H:2]([C:9]([NH:11][C@H:12]([C:21]([NH:23]N)=[O:22])[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=1)=[O:10])[CH2:3][O:4][C:5]([CH3:8])([CH3:7])[CH3:6].Cl.N(OC(C)(C)C)=O.C(N(C(C)C)C(C)C)C.N[C@@H:50]([C:61]([NH:63][C@H:64]([C:69]([NH:71][C@H:72]([C:80]([N:82]1[CH2:93][CH2:92][CH2:91][C@H:83]1[C:84]([NH:86][CH2:87][C:88]([NH2:90])=[O:89])=[O:85])=[O:81])[CH2:73][CH2:74][CH2:75][NH:76][C:77](=[NH:79])[NH2:78])=[O:70])[CH2:65][CH:66]([CH3:68])[CH3:67])=[O:62])[CH2:51][C:52]1[C:60]2[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=2)[NH:54][CH:53]=1.FC(C(O)=O)(F)F>CN(C)C=O.C(OCC)(=O)C>[NH:1]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C@H:2]([C:9]([NH:11][C@H:12]([C:21]([NH:23][C@@H:50]([C:61]([NH:63][C@H:64]([C:69]([NH:71][C@H:72]([C:80]([N:82]1[CH2:93][CH2:92][CH2:91][C@H:83]1[C:84]([NH:86][CH2:87][C:88]([NH2:90])=[O:89])=[O:85])=[O:81])[CH2:73][CH2:74][CH2:75][NH:76][C:77](=[NH:78])[NH2:79])=[O:70])[CH2:65][CH:66]([CH3:67])[CH3:68])=[O:62])[CH2:51][C:52]1[C:60]2[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=2)[NH:54][CH:53]=1)=[O:22])[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=1)=[O:10])[CH2:3][O:4][C:5]([CH3:8])([CH3:7])[CH3:6]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 10906Tert-Butyl nitriteHCID 81531Diisopropylethylamine2×HCID 12786121HCID 12786121, compoundHCID 178446015HCID 178446015, compound

Product 1

HCID 178445957HCID 178445957, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-15 °C

Procedure

To a solution of Boc-Ser(But)-Tyr-NHNH2 (3.68 g) in dimethylformamide (84 ml) at -15° C., was added a solution of hydrogen chloride in ethyl acetate (1.7 N, 12.35 ml), followed by t-butyl nitrite (1.17 ml). After stirring at -15° C. for 15 min, the reaction mixture was cooled to -25° C. and adjusted to pH 7 with N-ethyldiisopropylamine (3.95 ml). To this solution at -20° C. was added a solution of the above H-D-Trp-Leu-Arg-Pro-Gly-NH2 trifluoroacetate and N-ethyldiisopropylamine (1.46 ml) in dimethylformamide (27 ml). The reaction mixture was stirred at -15° C. for 60 min, at ice-bath temperature for 60 min and a room temperature for 18 hr. The solvent was evaporated and the residue was dissolved in methanol. Diethyl ether was added and the precipitate was chromatographed on silica gel using chloroform-methanol-32% aqueous acetic acid (15:4:1 v/v). The pure fractions were combined, evaporated and dried to give 5.4 g of Boc-Ser(But)-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH2 ; nmr (DMSO-D6)δ 0.75 (m, 6H), 1.05 (s, 9H) and 1.25 (s, 9H); uv max (methanol) 289 (ε=4546) and 279 nm (ε=5992); amino acid analysis: Gly (1.00), Arg (0.99), Trp (0.44), Ser (0.70), Pro (0.96), Leu (1.39) and Tyr (1.02); and [α]D25 -7.89° (c=1,1% acetic acid).

Workup

  1. temperaturethe reaction mixture was cooled to -25° C.
  2. stirringThe reaction mixture was stirred at -15° C. for 60 min, at ice-bath temperature for 60 min
  3. waita room temperature for 18 hr
  4. customThe solvent was evaporated
  5. dissolutionthe residue was dissolved in methanol
  6. additionDiethyl ether was added
  7. customthe precipitate was chromatographed on silica gel
  8. customevaporated
  9. customdried

Sources & evidence

ORD record
ord-105f8965df97430c8d598610bdc5f237
Source dataset
uspto-grants-1981_11
Patent number
US04301066

Reaction notes

Loading…