4-Methylmorpholine → HCID 25177236, compound

HRID 1811729Notes

Reaction equation

HRID 1811729 reaction equation
[NH2:1][C:2]1[N:21]=[C:20]2[CH:22]=[C:4]([C:5]3[CH:28]=[C:9]([C:10](=[O:27])[NH:11][C@H:12]([C:24](O)=[O:25])[CH2:13][CH2:14][NH:15][C:16](=[O:23])[CH2:17][CH2:18][S:19]2)[C:8]([CH3:29])=[CH:7][C:6]=3[CH3:30])[N:3]=1.C(OC(Cl)=O)C(C)C.CN1CCOCC1.[BH4-].[Na+]>O1CCCC1.CO.C(OCC)(=O)C>[NH2:1][C:2]1[N:21]=[C:20]2[CH:22]=[C:4]([C:5]3[CH:28]=[C:9]([C:10](=[O:27])[NH:11][C@H:12]([CH2:24][OH:25])[CH2:13][CH2:14][NH:15][C:16](=[O:23])[CH2:17][CH2:18][S:19]2)[C:8]([CH3:29])=[CH:7][C:6]=3[CH3:30])[N:3]=1

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 4311764Sodium borohydrideHCID 59224665HCID 59224665, compound

Product 1

HCID 25177236HCID 25177236, compoundYield 38.5%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S)-4-Amino-18,20-dimethyl-10,16-dioxo-7-thia-3,5,11,15-tetraazatricyclo[15.3.1.12,6]docosa-1(20),2(22),3,5,17(21),18-hexaene-14-carboxylic acid (550 mg, 1.28 mmol) obtained in Example 2-13 was dissolved in a mixture of tetrahydrofuran (13 ml) and methanol (1.5 ml). Isobutylchloroformate (250 μl, 1.92 mmol) and N-methylmorpholine (141 μl, 1.28 mmol) were added to the solution at room temperature. After stirring at room temperature for one hour, the mixture was cooled to 0° C. and an aqueous solution (1.5 ml) of sodium borohydride (97 mg, 2.56 mmol) was added thereto. The mixture was warmed to room temperature, and then diluted with ethyl acetate. The solution was sequentially washed with water and a saturated aqueous sodium chloride solution. The washed ethyl acetate solution was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (developing solvent: dichloromethane:methanol=10:1) to yield (S)-4-amino-14-hydroxymethyl-18,20-dimethyl-7-thia-3,5,11,15-tetraazatricyclo[15.3.1.12,6]docosa-1(20),2(22),3,5,17(21),18-hexaene-10,16-dione (Compound 68) (205 mg) as a white solid material.

Workup

  1. temperaturethe mixture was cooled to 0° C.
  2. temperatureThe mixture was warmed to room temperature
  3. washThe solution was sequentially washed with water
  4. dry with materialThe washed ethyl acetate solution was dried over anhydrous sodium sulfate
  5. filtrationAfter filtration
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe resulting crude product was purified by silica gel column chromatography (developing solvent: dichloromethane:methanol=10:1)

Sources & evidence

ORD record
ord-56418c1bd9d34d70923dcbebbe0bb599
Source dataset
uspto-grants-2013_01
Patent number
US08362236B2

Reaction notes

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