Morpholine → HCID 11213795, compound

HRID 1833109Notes

Reaction equation

HRID 1833109 reaction equation
C([O:3][C:4]([C:6]1[C:15]2[C:10](=[CH:11][C:12]([O:18][CH3:19])=[C:13]([O:16][CH3:17])[CH:14]=2)[C:9]([C:20](=[O:32])[C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([O:27][CH2:28][C:29](O)=[O:30])[CH:22]=2)=[N:8][CH:7]=1)=[O:5])C.[NH:33]1[CH2:38][CH2:37][O:36][CH2:35][CH2:34]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>C(Cl)Cl>[CH3:17][O:16][C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][C:12]=1[O:18][CH3:19])[C:9]([C:20](=[O:32])[C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([O:27][CH2:28][C:29]([N:33]3[CH2:38][CH2:37][O:36][CH2:35][CH2:34]3)=[O:30])[CH:22]=1)=[N:8][CH:7]=[C:6]2[C:4]([OH:3])=[O:5]

Participants

6

Reactant 4

HCID 8083MorpholineHCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 21034870HCID 21034870, compound

Product 1

HCID 11213795HCID 11213795, compoundYield 21%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-(3-carboxymethoxybenzoyl)-6,7-dimethoxy-isoquinoline-4-carboxylic acid ethyl ester (93.3 mg, 0.20 mmol) in 8 ml of methylene chloride was added 10 equivalent of morpholine, 1.2 equivalent of HBTU and 4 equivalent of triethylamine. The mixture was stirred at room temperature overnight. The solvents were evaporated and the residue was extracted with ethyl acetate and water. The organic phase was dried and solvents were evaporated. The residue was dissolved in 4 ml of methanol and aqueous lithium hydroxide was added (0.5N, 1 ml). The mixture was stirred overnight until all starting material disappeared. The reaction was loaded on a preparative HPLC for purification to give 6,7-Dimethoxy-1-[3-(2-morpholin-4-yl-2-oxo-ethoxy)-benzoyl]-isoquinoline-4-carboxylic acid as a fluffy solid (20 mg, 21%). ES-MS calcd for C25H24N2O8 (m/e) 480.5, obsd 481.3 (M+H).

Workup

  1. customThe solvents were evaporated
  2. extractionthe residue was extracted with ethyl acetate and water
  3. customThe organic phase was dried
  4. customsolvents were evaporated
  5. dissolutionThe residue was dissolved in 4 ml of methanol
  6. additionaqueous lithium hydroxide was added (0.5N, 1 ml)
  7. stirringThe mixture was stirred overnight until all starting material
  8. customThe reaction was loaded on a preparative HPLC for purification

Sources & evidence

ORD record
ord-65411c603f4d4a62af095bf146ac3d16
Source dataset
uspto-grants-2006_06
Patent number
US07067529B2

Reaction notes

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