1,2,3,4-Tetrahydroisoquinoline → HCID 67903286, compound

HRID 1029741Notes

Reaction equation

HRID 1029741 reaction equation
[F:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[CH2:8][CH2:9][CH2:10][NH:11][N:12]1[C:20]2[C:15](=[CH:16][C:17]([OH:21])=[CH:18][CH:19]=2)[C:14]([CH3:22])=[CH:13]1.[C:23](N1C=CN=C1)([N:25]1C=CN=C1)=[O:24].[CH2:35]1[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH2:38][CH2:37][NH:36]1.C([O-])(O)=O.[Na+]>O1CCCC1.C(O)(=O)C.CCOCC.CCOC(C)=O.ClCCl.CCOC(C)=O.CCCCCC>[CH2:35]1[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH2:38][CH2:37][N:36]1[NH:25][C:23](=[O:24])[O:21][C:17]1[CH:16]=[C:15]2[C:20](=[CH:19][CH:18]=1)[N:12]([NH:11][CH2:10][CH2:9][CH2:8][C:7]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[F:1])[CH:13]=[C:14]2[CH3:22]

Participants

10

Reactant 4

HCID 70461,2,3,4-Tetrahydroisoquinoline2×HCID 682631,1'-CarbonyldiimidazoleHCID 516892Sodium BicarbonateHCID 70146441HCID 70146441, compound

Product 1

HCID 67903286HCID 67903286, compound

Reagents, catalysts & solvents 5

HCID 176Acetic AcidSolvent3×HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent3×HCID 21226138Dichloromethane ethylacetateSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

To a stirred solution of 1-[(3-fluoro-4-pyridinyl)propylamino]-3-methyl-1H-indol-5-ol (2.51 g) in anhydrous tetrahydrofuran (56 ml) was added 1,1'-carbonyl diimidazole (2.72 g) at room temperature under nitrogen. After 24 hours the reaction appeared complete by TLC (silica gel, 60% EtOAc/hexane) and acetic acid (1.60 ml) was added to the reaction mixture followed by the dropwise addition of a solution of 1,2,3,4-tetrahydroisoquinoline (1.58 ml) in tetrahydrofuran (5.0 ml) and acetic acid (0.75 ml). After 72 hours, the reaction was not complete by TLC (60% EtOAc/dichloromethane) and an additional equivalent of 1,2,3,4-tetrahydroisoquinoline (1.05 ml) was added as a tetrahydrofuran (5.0 ml) and acetic acid (0.51 ml) solution. After 1.5 hours the reaction appeared complete and the mixture was poured into NaHCO3 (aq) and ether. The layers were separated and the aqueous phase was extracted with ether (3x). The combined organic layers were washed successively with NaHCO3 (aq) and brine, and dried (Na2SO4). The organic phase was filtered and concentrated to give a crude product. Purification via flash column chromatography (silica gel., 30% EtOAc/dichloromethane) afforded 2.70 g of the desired product as an oil which solidified on standing. Recrystallization from ether (2x) gave a solid which was filtered and washed with ether, m.p. 157°-160° C.

Workup

  1. additionwas added to the reaction mixture
  2. waitAfter 1.5 hours the reaction appeared complete
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted with ether (3x)
  5. washThe combined organic layers were washed successively with NaHCO3 (aq) and brine
  6. dry with materialdried (Na2SO4)
  7. filtrationThe organic phase was filtered
  8. concentrationconcentrated
  9. customto give a crude product
  10. customPurification via flash column chromatography (silica gel., 30% EtOAc/dichloromethane)

Sources & evidence

ORD record
ord-61224a8452a544b69fee6388b2a94aa8
Source dataset
uspto-grants-1992_04
Patent number
US05102891

Reaction notes

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