4-Methylmorpholine → HCID 86618344, compound

HRID 409566Notes

Reaction equation

HRID 409566 reaction equation
[O:1]=[C:2]1[N:7]([CH2:8][CH2:9][N:10]2[CH2:15][CH2:14][CH:13](C3C=CC=CC=3C(O)=O)[CH2:12][CH2:11]2)[C:6]2[CH:25]=[CH:26][CH:27]=[CH:28][C:5]=2[O:4][CH2:3]1.CN1[CH2:35][CH2:34][O:33]CC1.ON1[C:41]2[CH:42]=C[CH:44]=[CH:45][C:40]=2N=N1.[C:46]1([CH2:52][CH2:53][CH2:54][NH2:55])[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[O:1]=[C:2]1[N:7]([CH2:8][CH2:9][N:10]2[CH2:11][CH2:12][CH:13]([C:35]3([CH:42]=[CH:41][CH:40]=[CH:45][CH2:44]3)[C:34]([NH:55][CH2:54][CH2:53][CH2:52][C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)=[O:33])[CH2:14][CH2:15]2)[C:6]2[CH:25]=[CH:26][CH:27]=[CH:28][C:5]=2[O:4][CH2:3]1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 162593-PhenylpropylamineHCID 757711-HydroxybenzotriazoleHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59662178HCID 59662178, compound

Product 1

HCID 86618344HCID 86618344, compoundYield 531.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
4 °C

Procedure

Compound 3-1 (150 mg, 0.39 mmol) was dissolved in dry DMF (10 mL), and treated with N-methylmorpholine (162 μL, 1.5 mmol), 1-hydroxybenzotriazole (6.3 mg, 0.047 mmol), and phenylpropylamine (70 μL, 0.49 mmol). The reaction mixture was chilled to 4° C. in an ice bath, treated with HBTU (280 mg, 0.74 mmol), and stirred overnight, allowing it to warm to rt. The reaction mixture was poured into EtOAc (50 mL) and washed with 1 N sodium hydroxide solution (3×), 1 N hydrochloric acid solution (3×), and brine. The organic layer was dried over Na2SO4 and concentrated to give a crude product, which was purified on silica gel (elution with 90% EtOAc in hexane) to give Compound 3 (125 mg, 0.25 mmol, 64%) as a yellow oil. 1H NMR (300 MHz, CDCl3) δ 7.37-6.98 (m, 13H), 5.97 (t, J=6 Hz, 1H), 4.56 (s, 2H), 4.09 (t, J=7 Hz, 2H), 3.45 (t, J=7 Hz, 2H), 3.10-2.93 (m, 3H), 2.74-2.61 (m, 4H), 2.27, (t of d, J=8 and 3 Hz, 2H), 2.02-1.83 (m, 6H); MS (ES+) m/z 498.3 (M+1); Anal Calcd. for C31H35N3O3-0.18H2O-0.62 HCl: C, 71.13; H, 6.93; N, 8.03; H2O, 0.62. found C, 71.13; H, 6.90; N, 7.91; KF=0.60.

Workup

  1. temperatureto warm to rt
  2. washwashed with 1 N sodium hydroxide solution (3×), 1 N hydrochloric acid solution (3×), and brine
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated
  5. customto give a crude product, which
  6. customwas purified on silica gel (elution with 90% EtOAc in hexane)

Sources & evidence

ORD record
ord-b8d9b238110a47d1a6e4d55ebe14fc61
Source dataset
uspto-grants-2014_06
Patent number
US08759342B2

Reaction notes

Loading…