Methylamine → HCID 117748919, compound

HRID 1775886Notes

Reaction equation

HRID 1775886 reaction equation
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@H:19]([CH2:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C:20]([OH:22])=O)=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.CN.C[CH2:34][N:35](C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH:10]1[C:11]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@@H:19]([C:20]([NH:35][CH3:34])=[O:22])[CH2:23][C:24]([O:26][C:27]([CH3:29])([CH3:30])[CH3:28])=[O:25])=[O:17])[C:13]3[C:5](=[CH:4][CH:3]=[CH:2][CH:1]=3)[C:6]=2[CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 6329MethylamineHCID 81531DiisopropylethylamineHCID 70188164-tert-Butyl N-((9H-Fluoren-9-ylmethoxy)carbonyl)-D-aspartateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 117748919HCID 117748919, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Prepared using General Procedure 7. To a stirring solution of (R)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-(tert-butoxy)-4-oxobutanoic acid (308 mg, 0.75 mmol), methylamine (40 wt % in water, 174 μL, 2.25 mmol), and DIEA (415 μl, 2.25 mmol) in DMF (7.5 mL) cooled to 0° C. was added HATU (569 mg, 1.5 mmol). The reaction mixture was allowed to warm slowly and stirring continued for 18 h. The reaction mixture was poured onto ice-water and the solid was filtered. The solid was dissolved in DCM (10 mL), dried over MgSO4 and evaporated. The crude product was purified by column chromatography to afford 226 mg (71%) of tert-butyl (R)-3-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-(methylamino)-4-oxobutanoate. LCMS-ESI (m/z) calculated for C24H28N2O5: 424.2. found 447.1 [M+Na]+, tR=3.12 min. (Method 16).

Workup

  1. customPrepared
  2. temperatureto warm slowly
  3. additionThe reaction mixture was poured onto ice-water
  4. filtrationthe solid was filtered
  5. dissolutionThe solid was dissolved in DCM (10 mL)
  6. dry with materialdried over MgSO4
  7. customevaporated
  8. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-4b75d0458fc14e9594178beeee53d66e
Source dataset
uspto-grants-2016_02
Patent number
US09260427B2

Reaction notes

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