Methylamine → Benzyl {2-[(tert-butoxycarbonyl)amino]-3-(methylamino)-3-oxopropyl}carbamate

HRID 1504819Notes

Reaction equation

HRID 1504819 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH2:12][C@@H:13]([C:22]([OH:24])=O)[NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:25][N:26](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN.C(N(CC)CC)C>CN(C=O)C.O>[C:18]([O:17][C:15]([NH:14][CH:13]([C:22]([NH:26][CH3:25])=[O:24])[CH2:12][NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:16])([CH3:19])([CH3:20])[CH3:21]

Participants

7

Reactant 4

HCID 6329MethylamineHCID 8471TriethylamineHCID 2755950Boc-dap(Z)-OHHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 69717545Benzyl {2-[(tert-butoxycarbonyl)amino]-3-(methylamino)-3-oxopropyl}carbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-{[(benzyloxy)carbonyl]amino}-N-(tert-butoxycarbonyl)alanine (10.0 g, 30.0 mmol) in DMF (100 mL) was added HATU (14.0 g, 36.0 mmol). After 2 hours, methylamine (4.1 g, 60 mmol) and triethylamine (15.0 g, 149 mol) were added. After 16 hours, the reaction mixture was diluted with water and the aqueous layer was extracted with ethyl acetate (3×100 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified via reverse phase HPLC (acetonitrile/water with 0.1% TFA, linear gradient) to give benzyl {2-[(tert-butoxycarbonyl)amino]-3-(methylamino)-3-oxopropyl}carbamate. MS ESI calc'd. for C17H26N3O5 [M+H]+ 352. found 352. 1H NMR (300 MHz, CDCl3) δ 7.33-7.31 (m, 5H), 6.59-6.57 (m, 1H), 5.69-5.66 (m, 1H), 5.42-5.39 (m, 1H), 5.14-5.05 (m, 2H), 4.19-4.16 (m, 1H), 3.63-3.41 (m, 2H), 2.78 (d, J=4.8 Hz, 3H), 1.43 (s, 9H).

Workup

  1. waitAfter 16 hours
  2. extractionthe aqueous layer was extracted with ethyl acetate (3×100 mL)
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified via reverse phase HPLC (acetonitrile/water with 0.1% TFA, linear gradient)

Sources & evidence

ORD record
ord-79ac8100cb354310b7a6115ed2c35c88
Source dataset
uspto-grants-2015_12
Patent number
US09216173B2

Reaction notes

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