Triethylamine → HCID 67350460, compound

HRID 1672831Notes

Reaction equation

HRID 1672831 reaction equation
[CH3:1][S:2][C:3]1[N:4]=[CH:5][C:6]2[C:15](=[O:16])[N:14]([C:17]3[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=3)C(O)=O)[CH2:13][C@H:12]3[N:8]([CH2:9][CH2:10][CH2:11]3)[C:7]=2[N:26]=1.Cl.[CH3:28][O:29][C:30](=[O:36])[C@H:31]([C@@H:33]([CH3:35])[OH:34])[NH2:32].[CH2:37](N(CC)CC)C.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.S(Cl)(Cl)=O.C(=O)(O)[O-].[Na+]>ClCCl.C(Cl)(Cl)Cl>[CH3:35][C@@H:33]1[O:34][C:37]([C:19]2[CH:23]=[CH:24][CH:25]=[C:17]([N:14]3[CH2:13][C@H:12]4[N:8]([CH2:9][CH2:10][CH2:11]4)[C:7]4[N:26]=[C:3]([S:2][CH3:1])[N:4]=[CH:5][C:6]=4[C:15]3=[O:16])[CH:18]=2)=[N:32][C@@H:31]1[C:30]([O:29][CH3:28])=[O:36]

Participants

10

Reactant 7

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2734893Methyl L-threoninate hydrochlorideHCID 67350552HCID 67350552, compound

Product 1

HCID 67350460HCID 67350460, compound

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

(S)-3-(9-Methylthio-6-oxo-2,3,3a,4-tetrahydro-1H,6H-5,8,10,10b-tetraazabenzo[e]azulen-5-yl)benzoic acid (2.00 g, 5.40 mmol) obtained in Step 1 of Example 56 was dissolved in dichloromethane (80 mL), and the mixture was stirred for 4 hours after adding L-threonine methyl ester hydrochloride (3.11 g, 16.2 mmol), triethylamine (2.26 mL, 16.2 mmol), 1-ethyl-3-(3dimethylaminopropyl)carbodiimide hydrochloride (1.24 g, 6.48 mmol), and 1-hydroxybenzotriazole.monohydrate (827 mg, 5.40 mmol). The mixture was diluted by addition of chloroform, and washed with a saturated aqueous sodium bicarbonate solution. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane (80 mL), cooled to 0° C., and stirred at room temperature for 4.5 hours after adding thionyl chloride (2.85 mL, 3.91 mmol). Then, the mixture was poured into a saturated aqueous sodium bicarbonate solution, and extracted with chloroform. The organic layer was then dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give methyl (4S,5S)-5-methyl-2-[3-((S)-9-methylthio-6-oxo-2,3,3a,4-tetrahydro-1H,6H-5,8,10,10b-tetraazabenzo[e]azulen-5-yl)phenyl]-4,5-dihydro-1,3-oxazole-4-carboxylate as a crude product. Using methyl (4S,5S)-5-methyl-2-[3-((S)-9-methylthio-6-oxo-2,3,3a,4-tetrahydro-1H,6H-5,8,10,10b-tetraazabenzo[e]azulen-5-yl)phenyl]-4,5-dihydrooxazole-4-carboxylate so obtained, methyl (S)-5-methyl-2-[3-(9-methylthio-6-oxo-2,3,3a,4-tetrahydro-1H,6H-5,8,10,10b-tetraazabenzo[e]azulen-5-yl)phenyl]-1,3-oxazole-4-carboxylate (2.04 g, 81%) was obtained in the same manner as in Step 2 of Example 123.

Workup

  1. washwashed with a saturated aqueous sodium bicarbonate solution
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe resulting residue was dissolved in dichloromethane (80 mL)
  5. stirringstirred at room temperature for 4.5 hours
  6. extractionextracted with chloroform
  7. dry with materialThe organic layer was then dried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b92f9716233d43419b636fed8d5ff3eb
Source dataset
uspto-grants-2011_08
Patent number
US07998954B2

Reaction notes

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