HCID 131712067, compound → HCID 131712066, compound

HRID 1389688Notes

Reaction equation

HRID 1389688 reaction equation
[NH:1](C(OCC1C=CC=CC=1)=O)[C@H:2]([C:15]([NH:17][C@H:18]([C:26]([NH:28][C@H:29]([C:37]([NH:39][C@H:40]([C:48]([NH:50][C@H:51]([C:58]([O:60][CH3:61])=[O:59])[CH2:52][O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:49])[C@@H:41]([CH3:47])[O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:38])[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:27])[C@@H:19]([CH3:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:16])[CH2:3][CH2:4][CH2:5][CH2:6][NH:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].[H][H]>[Pd].C(O)(=O)C>[NH2:1][C@H:2]([C:15]([NH:17][C@H:18]([C:26]([NH:28][C@H:29]([C:37]([NH:39][C@H:40]([C:48]([NH:50][C@H:51]([C:58]([O:60][CH3:61])=[O:59])[CH2:52][O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:49])[C@@H:41]([CH3:47])[O:42][C:43]([CH3:44])([CH3:45])[CH3:46])=[O:38])[CH2:30][C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)=[O:27])[C@@H:19]([CH3:25])[O:20][C:21]([CH3:24])([CH3:22])[CH3:23])=[O:16])[CH2:3][CH2:4][CH2:5][CH2:6][NH:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9]

Participants

5

Reactant 2

HCID 131712067HCID 131712067, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 131712066HCID 131712066, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolvent

Procedure

A mixture of Z-Lys(Boc)-Thr(But)-Phe-Thr(But)-Ser(But)-OMe (32.8 g, 0.033 mole, described in U.S. Pat. No. 3,917,578, cited above) and 5% palladium on carbon (1.65 g) in acetic acid (328 ml) was rapidly stirred under one atmosphere of hydrogen until the benzyloxycarbonyl group was removed. The mixture was filtered and the filtrate was evaporated to give a residue of H-Lys(Boc)-Thr(But)-Phe-Thr(But)-Ser(But)-OMe.HOAc. A mixture of benzyloxycarbonyl-D-tryptophan (14.5 g, 0.0428 mole) and 1-hydroxybenzotriazole (11.56 g, 0.0856 mole) in tetrahydrofuran (428 ml) at -10° C. and a mixture of dicyclohexylcarbodiimide (17.62 g, 0.0856 mole) in tetrahydrofuran (51 ml) were mixed together. The resulting mixture was stirred at 0° C. for one hr and at 25° C. for one hr. A solution of the above residue in tetrahydrofuran (150 ml) was adjusted to pH 7.5 with N-ethylmorpholine at 0° C. and added to the above mixture. The resulting mixture was stirred at 25° C. for 24 hr and filtered. The precipitate (A) was washed with ethyl acetate. The filtrate and ethyl acetate washings were washed with 1 N hydrochloric acid, water and saturated sodium bicarbonate, dried over magnesium sulfate and evaporated to give 8.8 g of the title compound and a mother liquor (B). Precipitate (A) was extracted with 3% methanol in chloroform. The extract was washed with 1 N hydrochloric acid, water and saturated sodium bicarbonate, dried over anhydrous magnesium sulfate and concentrated to give a precipitate (C) and mother liquor (D). Mother liquors (B) and (D) were concentrated to give another 10 g of the title compound. Precipitate (C) was triturated with 10% methanol in benzene and the insoluble material was discarded. The filtrate was concentrated to give another 15.9 g of the title compound: [α]D +20.7° (C=1, dimethylformamide), nmr(CDCl3) δ 1.15(s), 1.25(s), 1.5(s), 3.65(s), 5.1(m) and 7.2(m), and amino acid analysis: Lys(1.05), Thr(2.01), Ser(1.07) and Phe(1.00).

Workup

  1. customwas removed
  2. filtrationThe mixture was filtered
  3. customthe filtrate was evaporated

Sources & evidence

ORD record
ord-d6beffb36b9240ec8c6452c677908f63
Source dataset
uspto-grants-1981_01
Patent number
US04244947

Reaction notes

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