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 1874039Notes

Reaction equation

HRID 1874039 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-233ca4b7ffbd402c907616df04fbadcc
Source dataset
uspto-grants-2012_11
Patent number
US08304546B2

Reaction notes

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