Dimethylformamide → 2-[3-(4-methoxyphenyl)-4-oxo-10-propoxy-7,8-dihydro-4H,6H-5-oxa-1-aza-phenanthren-1-yl]-N-(2-morpholin-4-ylethyl)acetamide

HRID 68147Notes

Reaction equation

HRID 68147 reaction equation
[NH2:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][O:7][CH2:6][CH2:5]1.CN(C=O)C.[CH3:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[C:36](=[O:37])[C:35]3[C:26](=[C:27]([O:38][CH2:39][CH2:40][CH3:41])[CH:28]=[C:29]4[C:34]=3[O:33][CH2:32][CH2:31][CH2:30]4)[N:25]([CH2:42][C:43](O)=[O:44])[CH:24]=2)=[CH:19][CH:18]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>C(N(CC)CC)C>[CH3:15][O:16][C:17]1[CH:18]=[CH:19][C:20]([C:23]2[C:36](=[O:37])[C:35]3[C:26](=[C:27]([O:38][CH2:39][CH2:40][CH3:41])[CH:28]=[C:29]4[C:34]=3[O:33][CH2:32][CH2:31][CH2:30]4)[N:25]([CH2:42][C:43]([NH:1][CH2:2][CH2:3][N:4]3[CH2:9][CH2:8][O:7][CH2:6][CH2:5]3)=[O:44])[CH:24]=2)=[CH:21][CH:22]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 4082852-MorpholinoethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58492449HCID 58492449, compound

Product 1

HCID 674604752-[3-(4-methoxyphenyl)-4-oxo-10-propoxy-7,8-dihydro-4H,6H-5-oxa-1-aza-phenanthren-1-yl]-N-(2-morpholin-4-ylethyl)acetamideYield 16%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

4-(2-Aminoethyl)morpholine (217 mg, 1.7 mmol) was added to a DMF solution (10 ml) of [3-(4-methoxyphenyl)-4-oxo-10-propoxy-7,8-dihydro-4H,6H-5-oxa-1-aza-phenanthren-1-yl]acetic acid (580 mg, 1.39 mmol), 2-(7-aza-1H-benzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate (HATU, 790 mg, 2.1 mmol) and triethylamine (5 ml). The mixture was stirred overnight at room temperature and then concentrated under reduced pressure. Water and ethyl acetate were added to the residue, followed by separation. The thus-obtained organic layer was washed with water and concentrated under reduced pressure. The residue was purified using silica gel column chromatography (dichloromethane:methanol=10:1). The purified product was concentrated under reduced pressure, and the residue was recrystallized from ethyl acetate, giving a pale brown powder of 2-[3-(4-methoxyphenyl)-4-oxo-10-propoxy-7,8-dihydro-4H,6H-5-oxa-1-aza-phenanthren-1-yl]-N-(2-morpholin-4-ylethyl)acetamide (115 mg, yield: 16%).

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionWater and ethyl acetate were added to the residue
  3. customfollowed by separation
  4. washThe thus-obtained organic layer was washed with water
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified
  7. concentrationThe purified product was concentrated under reduced pressure
  8. customthe residue was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-64f1f98f6e324a17a8329873ce2fb169
Source dataset
uspto-grants-2014_09
Patent number
USRE045108E1

Reaction notes

Loading…