Methylamine → HCID 25177310, compound

HRID 1811727Notes

Reaction equation

HRID 1811727 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]([OH:26])=O)[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.O[N:32]1[C:36]2C=CC=CC=2N=N1.CN.Cl.C(N=C=NCCCN(C)C)C.C(N(C(C)C)CC)(C)C>CN(C)C=O.C(OCC)(=O)C>[CH3:36][NH:32][C:24]([C@H:12]1[NH:11][C:10](=[O:27])[C:9]2=[CH:28][C:5](=[C:6]([CH3:30])[CH:7]=[C:8]2[CH3:29])[C:4]2=[CH:22][C:20](=[N:21][C:2]([NH2:1])=[N:3]2)[S:19][CH2:18][CH2:17][C:16](=[O:23])[NH:15][CH2:14][CH2:13]1)=[O:26]

Participants

8

Reactant 5

HCID 6329MethylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 59224665HCID 59224665, compound

Product 1

HCID 25177310HCID 25177310, compoundYield 27.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 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 (25 mg, 0.058 mmol) obtained in Example 2-13 and 1-hydroxybenzotriazole (24 mg, 0.175 mmol) were dissolved in N,N-dimethylformamide (580 μl). Methylamine (2.0 M tetrahydrofuran solution, 88 μl, 0.175 mmol), 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (34 mg, 0.175 mmol), and diisopropylethylamine (0.073 ml, 0.42 mmol) were added to the solution. The resulting mixture was stirred overnight at room temperature. The reaction solution was diluted with ethyl acetate, and sequentially washed with a saturated aqueous sodium bicarbonate solution, water (three times), and a saturated aqueous sodium chloride solution. The washed organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The resulting crude product was purified by preparative thin layer silica gel chromatography (developing solvent: dichloromethane:methanol=10:1) to yield (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 methylamide (Compound 65) (7 mg) was obtained as a white solid material.

Workup

  1. washsequentially washed with a saturated aqueous sodium bicarbonate solution, water (three times)
  2. dry with materialThe washed organic layer was dried over anhydrous sodium sulfate
  3. filtrationAfter filtration
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe resulting crude product was purified by preparative thin layer silica gel chromatography (developing solvent: dichloromethane:methanol=10:1)

Sources & evidence

ORD record
ord-f1fb3fb303ee4d2fb1081933468d0cf1
Source dataset
uspto-grants-2013_01
Patent number
US08362236B2

Reaction notes

Loading…