cis-5-amino-N-[1-(3-aminopropyl)-3-methoxy-4-piperidinyl]-6-chloro-3,4-dihydro-2H-1-benzopyran-8-carboxamide → HCID 178496716, compound

HRID 742826Notes

Reaction equation

HRID 742826 reaction equation
[NH2:1][C:2]1[C:7]2[CH2:8][CH2:9][CH2:10][O:11][C:6]=2[C:5]([C:12]([NH:14][C@H:15]2[CH2:20][CH2:19][N:18]([CH2:21][CH2:22][CH2:23][NH2:24])[CH2:17][C@H:16]2[O:25][CH3:26])=[O:13])=[CH:4][C:3]=1[Cl:27].CS[C:30]1[N:35]=[C:34]([OH:36])[CH:33]=[CH:32][N:31]=1>C(#N)C>[OH2:11].[NH2:1][C:2]1[C:7]2[CH2:8][CH2:9][CH2:10][O:11][C:6]=2[C:5]([C:12]([NH:14][C@H:15]2[CH2:20][CH2:19][N:18]([CH2:21][CH2:22][CH2:23][NH:24][C:30]3[N:35]=[C:34]([OH:36])[CH:33]=[CH:32][N:31]=3)[CH2:17][C@H:16]2[O:25][CH3:26])=[O:13])=[CH:4][C:3]=1[Cl:27].[NH2:1][C:2]1[C:7]2[CH2:8][CH2:9][CH2:10][O:11][C:6]=2[C:5]([C:12]([NH:14][C@H:15]2[CH2:20][CH2:19][N:18]([CH2:21][CH2:22][CH2:23][NH:24][C:30]3[N:35]=[C:34]([OH:36])[CH:33]=[CH:32][N:31]=3)[CH2:17][C@H:16]2[O:25][CH3:26])=[O:13])=[CH:4][C:3]=1[Cl:27]

Participants

4

Reactant 2

HCID 67704546cis-5-amino-N-[1-(3-aminopropyl)-3-methoxy-4-piperidinyl]-6-chloro-3,4-dihydro-2H-1-benzopyran-8-carboxamideHCID 178503462HCID 178503462, compound

Product 1

HCID 178496716HCID 178496716, compoundYield 35.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 5 parts of cis-5-amino-N-[1-(3-aminopropyl)-3-methoxy-4-piperidinyl]-6-chloro-3,4-dihydro-2H-1-benzopyran-8-carboxamide, 3.2 parts of 2-methylthio-4-pyrimidinol and 79 parts of acetonitrile was stirred over weekend at reflux temperature. The reaction mixture was evaporated and the residue was partitioned between dichloromethane and ammonia (aq.). The aqueous layer was separated and re-extracted with dichloromethane (2×). The combined dichloromethane layers were dried, filtered and evaporated. The residue was purified by column chromatography (silica gel; CH2Cl2 /CH3OH(NH3) 95:5). The eluent of the two desired fractions was evaporated and the residues were separately crystallized from acetonitrile. The product was filtered off and dried in vacuo at 70° C., yielding a first fraction of 2.22 parts (35.2%) of cis-5-amino-6-chloro-3,4-dihydro-N-[1-[3-[(4-hydroxy-2-pyrimidinyl)amino]propyl]-3-methoxy-4-piperidinyl]-2H-1-benzopyran-8-carboxamide hemihydrate; mp. 142.6° C. and a second fraction of 1.00 part (15.9%) of cis-5-amino-6-chloro-3,4-dihydro-N-[1-[3-[(4-hydroxy-2-pyrimidinyl)amino]propyl]-3-methoxy-4-piperidinyl]-2H-1-benzopyran-8-carboxamide hemihydrate; mp. 143.5° C. Total yield: 3.22 parts (51.1%) of product (comp. 128).

Workup

  1. temperatureat reflux temperature
  2. customThe reaction mixture was evaporated
  3. customthe residue was partitioned between dichloromethane and ammonia (aq.)
  4. customThe aqueous layer was separated
  5. extractionre-extracted with dichloromethane (2×)
  6. dry with materialThe combined dichloromethane layers were dried
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by column chromatography (silica gel; CH2Cl2 /CH3OH(NH3) 95:5)
  10. customThe eluent of the two desired fractions was evaporated
  11. customthe residues were separately crystallized from acetonitrile
  12. filtrationThe product was filtered off
  13. customdried in vacuo at 70° C.

Sources & evidence

ORD record
ord-64223d705ace4ba88637588f8e541c09
Source dataset
uspto-grants-1996_09
Patent number
US05554772

Reaction notes

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