4-Methylmorpholine → HCID 67148370, compound

HRID 1054006Notes

Reaction equation

HRID 1054006 reaction equation
[C:1]([NH:8][C@H:9]([C:13]([OH:15])=O)[CH:10]([CH3:12])[CH3:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[CH2:47]([O:49][C:50](=[O:68])[CH2:51][CH2:52][C:53]1[O:54][C:55]2[CH:67]=[CH:66][CH:65]=[CH:64][C:56]=2[C:57]=1[CH2:58][CH:59]1[CH2:63][CH2:62][CH2:61][NH:60]1)[CH3:48]>CN1C(=O)CCC1.C(OCC)C>[CH2:47]([O:49][C:50](=[O:68])[CH2:51][CH2:52][C:53]1[O:54][C:55]2[CH:67]=[CH:66][CH:65]=[CH:64][C:56]=2[C:57]=1[CH2:58][CH:59]1[CH2:63][CH2:62][CH2:61][N:60]1[C:13](=[O:15])[CH:9]([NH:8][C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])[CH:10]([CH3:11])[CH3:12])[CH3:48]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 83693Boc-L-ValineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67148063HCID 67148063, compound

Product 1

HCID 67148370HCID 67148370, compoundYield 96.8%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

A solution containing Boc-L-valine (352 mg, 1.6 mmol) in NMP (3 mL) was treated with HATU (543 mg, 1.4 mmol) followed by NMM (0.2 mL, 1.8 mmol) at ambient temperature. After 10 min, amine 48 (0.4 g, 1.3 mmol) in NMP (5 mL) was added in a dropwise fashion. After 16 h, the reaction mixture was diluted with diethyl ether and washed successively with NaHCO3, 1 M HCl, water, and brine. The organic extract was dried over anhydrous Na2SO4, filtered and concentrated to afford 630 mg (96%) of 49 which was used without further purification. 1H NMR (CDCl3, 300 MHz) δ7.82-7.79 (m, 1H), 7.38-7.35 (m, 1H), 7.28-7.21 (m, 2H), 5.37 (d, J=9.3 Hz, 1H), 4.50-4.44 (m, 1H), 4.31 (dd, J=6.0, 9.0 Hz, 1H), 4.14 (q, J=6.9 Hz, 2H), 3.72-3.60 (m, 3H), 3.38 (t, J=7.2 Hz, 1H), 3.29 (dd, J=3.0, 13.5 Hz, 1H), 3.12 (app t, J=7.5 Hz, 2H), 2.80-2.74 (m, 4H), 2.46-2.35 (m, 2H), 2.11-1.92 (m, 2H), 1.81-1.73 (m, 1H), 1.69-1.65 (m, 1H), 1.44 (s, 9H), 1.25 (t, J=6.0 Hz, 3H), 1.03 (d, J=6.3 Hz, 3H), 0.96 (d, J=6.6 Hz, 3H) ppm. Mass spectrum: m/z 501 [M+H]+; and, 523 [M+Na]+.

Workup

  1. waitAfter 16 h
  2. washwashed successively with NaHCO3, 1 M HCl, water, and brine
  3. extractionThe organic extract
  4. dry with materialwas dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-f1e8ccab3eda430cb140cfac8cc57acb
Source dataset
uspto-grants-2016_07
Patent number
US09394249B2

Reaction notes

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