Ethylmorpholine → HCID 178445964, compound

HRID 1155458Notes

Reaction equation

HRID 1155458 reaction equation
[NH:1]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C@@H:2]([C:13]([OH:15])=O)[CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1.C1(N=C=NC2CCCCC2)CCCCC1.ON1C2C=CC=CC=2N=N1.[NH2:48][C@H:49]([C:54]([NH:56][C@H:57]([C:65]([N:67]1[CH2:78][CH2:77][CH2:76][C@H:68]1[C:69]([NH:71][CH2:72][C:73]([NH2:75])=[O:74])=[O:70])=[O:66])[CH2:58][CH2:59][CH2:60][NH:61][C:62](=[NH:64])[NH2:63])=[O:55])[CH2:50][CH:51]([CH3:53])[CH3:52].CC(O)=O.CC(O)=O.C(N1CCOCC1)C>CN(C)C=O>[NH:1]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C@@H:2]([C:13]([NH:48][C@H:49]([C:54]([NH:56][C@H:57]([C:65]([N:67]1[CH2:78][CH2:77][CH2:76][C@H:68]1[C:69]([NH:71][CH2:72][C:73]([NH2:75])=[O:74])=[O:70])=[O:66])[CH2:58][CH2:59][CH2:60][NH:61][C:62](=[NH:63])[NH2:64])=[O:55])[CH2:50][CH:51]([CH3:52])[CH3:53])=[O:15])[CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1

Participants

7

Reactant 5

HCID 7525EthylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 111050N-((tert-Butoxy)carbonyl)-D-tryptophanHCID 178476510HCID 178476510, compound

Product 1

HCID 178445964HCID 178445964, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of Boc-D-Trp-OH (5.5 g), dicyclohexylcarbodiimide (4.05 g) and 1-hydroxybenzotriazole (3.6 g) in dimethylformamide (70 ml) was stirred at ice-bath temperature for 90 min. A solution of H-Leu-Arg-Pro-Gly-NH2 diacetate (10 g, described by H. U. Immer et al., U.S. Pat. No. 3,835,108, cited above) in dimethylformamide (60 ml) was adjusted to pH 8 with N-ethylmorpholine and added to the above solution. The resulting mixture was stirred at room temperature overnight and filtered. The filtrate was evaporated and the residue was dissolved in methanol. Diethyl ether was added and the precipitate was collected and chromatographed on silica gel using chloroform-methanol-35% aqueous acetic acid (5:3:1 v/v). The pure fractions were collected and evaporated. The residue was dissolved in methanol and diethyl ether was added. The precipitate was collected and dried to give 7.8 g of Boc-D-Trp-Leu-Arg-Pro-Gly-NH2 ; nmr (DMSO-D6)δ 0.80 (m, 6H) and 1.30 (s, 9H); uv max (methanol) 289 (ε=4433) and 281 nm (ε=5015); and amino acid analysis: Gly (1.00), Pro (0.98), Leu (0.97), Arg (0.95) and Trp (0.63); and [α]D25 -16.89° (c=1, 1% acetic acid).

Workup

  1. additionadded to the above solution
  2. filtrationfiltered
  3. customThe filtrate was evaporated
  4. dissolutionthe residue was dissolved in methanol
  5. additionDiethyl ether was added
  6. customthe precipitate was collected
  7. customchromatographed on silica gel
  8. customThe pure fractions were collected
  9. customevaporated
  10. dissolutionThe residue was dissolved in methanol
  11. additiondiethyl ether was added
  12. customThe precipitate was collected
  13. customdried

Sources & evidence

ORD record
ord-9280607ec3ac4cf6a7997f4ad404b86b
Source dataset
uspto-grants-1981_11
Patent number
US04301066

Reaction notes

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