Methanol → HCID 59926879, compound

HRID 2121261Notes

Reaction equation

HRID 2121261 reaction equation
[OH-:1].[Na+].[CH3:3][O:4][C:5](=[O:12])[C@H:6]([CH2:8][CH2:9][S:10][CH3:11])[NH2:7].[CH3:13][CH2:14][N:15]=[C:16]=[N:17][CH2:18][CH2:19]CN(C)C.[CH:24]1[CH:25]=[CH:26][C:27]2N(O)N=N[C:28]=2[CH:29]=1.[CH3:34][OH:35]>C(Cl)Cl>[CH3:3][O:4][C:5](=[O:12])[C@H:6]([CH2:8][CH2:9][S:10][CH3:11])[NH:7][C:34](=[O:35])[C:27]1[CH:26]=[CH:25][C:24]([O:1][CH2:19][CH2:18][N:17]2[CH:13]=[CH:14][N:15]=[CH:16]2)=[CH:29][C:28]=1[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

7

Reactant 5

HCID 887MethanolHCID 14798Sodium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 64684methyl (2S)-2-amino-4-(methylsulfanyl)butanoateHCID 757711-Hydroxybenzotriazole

Product 1

HCID 59926879HCID 59926879, compoundYield 99%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The compound prepared in Example 957C (738 mg, 2.29 mmol) was dissolved in 5 mL of methanol. To this solution was added 4.5 mL of 1N NaOH solution and the mixture was refluxed for 5 hr. The solution was filtered and the filtrate was acidified with 1 N aqueous HCl to PH about 4.2. After cooling in ice bath, white crystals were collected (701 mg, 99% yield). m.p 242-244° C. This carboxylic acid (250 mg, 0.81 mmol) was coupled with (L)-methionine methyl ester in methylene chloride by using coupling reagent EDCI and HOBT. After the work up with sodium bicarbonate solution, the residue was purified by flash column chromatography (6% methanol in methylene chloride) to give the title compound as a white foam solid (340 mg, 93% yield). 1H NMR (CDCl3) δ 7.66 (d, J 8.6 Hz, 1H), 7.54 (s, 1H), 7.34-7.42 (m, 5H), 7.01 (br s, 2H), 6.85 (d, J=8.6 Hz, 1H), 6.76 (s, 1H), 6.00 (d, J=7.7 Hz, 1H), 4.60 (ddd, J=5.3, 5.7 and 7.7 Hz, 1H), 4.30 (t, J=4.9 Hz, 2H), 4.21 (t, J=4.9 Hz, 2H), 3.62 (s, 3H), 2.05 (t, J=7.6 hz, 2H), 1.97 (s, 3H), 1.81-1.92 (m, 1H), 1.61-1.73 (m, 1H); 13C NMR (CDCl3): δ 171.6, 168.3, 158.6, 141.5, 139.6, 137.0, 130.4, 128.8, 128.2, 127.9, 127.6, 119.0, 115.8, 112.8, 67.0, 51.9, 51.4, 45.8, 30.8, 19.1, 14.8.

Workup

  1. temperaturethe mixture was refluxed for 5 hr
  2. filtrationThe solution was filtered
  3. temperatureAfter cooling in ice bath
  4. customwhite crystals were collected (701 mg, 99% yield)
  5. customm.p 242-244° C
  6. customAfter the work up with sodium bicarbonate solution, the residue was purified by flash column chromatography (6% methanol in methylene chloride)

Sources & evidence

ORD record
ord-82c2767253c34ebaa9c4fdb998d5d170
Source dataset
uspto-grants-2004_02
Patent number
US06693123B2

Reaction notes

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