Dichloromethane → HCID 22048404, compound

HRID 1833107Notes

Reaction equation

HRID 1833107 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]([OH:31])=O)[CH:22]=2)=[N:8][CH:7]=1)=[O:5])C.C(Cl)Cl.[NH:36]1[CH2:40][CH2:39][CH2:38][CH2:37]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>>[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](=[O:31])[N:36]3[CH2:40][CH2:39][CH2:38][CH2:37]3)[CH:22]=1)=[N:8][CH:7]=[C:6]2[C:4]([OH:3])=[O:5]

Participants

6

Reactant 5

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 31268PyrrolidineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 21034870HCID 21034870, compound

Product 1

HCID 22048404HCID 22048404, compoundYield 33%

Procedure

The above 1-(3-carboxymethoxybenzoyl)-6,7-dimethoxy-isoquinoline-4-carboxylic acid ethyl ester (88.5 mg, 0.19 mmol) was suspended in 8 ml of methylene chloride containing 10 equivalent of pyrrolidine, 2.0 equivalent of HBTU and 3.0 equivalent of triethylamine. The mixture was stirred at room temperature overnight and then evaporated to remove solvents. The residue was extracted with ethyl acetate and water. The organic layer 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 to a preparative HPLC for purification to give 6,7-Dimethoxy-1-[3-(2-oxo-2-pyrrolidin-1-yl-ethoxy)-benzoyl]-isoquinoline-4-carboxylic acid as a fluffy solid (29 mg, 33%). ES-MS calcd for C25H24N2O7 (m/e) 464.5, obsd 465.4 (M+H).

Workup

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

Sources & evidence

ORD record
ord-330f369bc15e4cfaaada644b5a1e76df
Source dataset
uspto-grants-2006_06
Patent number
US07067529B2

Reaction notes

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