Cesium carbonate → HCID 60164039, compound

HRID 1620257Notes

Reaction equation

HRID 1620257 reaction equation
FC(F)(F)S(O[C:7]1[N:8]=[C:9]([CH2:35][CH2:36][CH3:37])[C:10]2[C:15]([C:16]=1[CH2:17][C:18]1[CH:30]=[CH:29][C:21]3[O:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[C:20]=3[CH:19]=1)=[CH:14][C:13]([O:31][CH3:32])=[C:12]([O:33][CH3:34])[CH:11]=2)(=O)=O.C(=O)(OC(C)(C)C)[NH2:41].C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1COCC1>[CH:19]1[C:20]2[C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=3[O:22][C:21]=2[CH:29]=[CH:30][C:18]=1[CH2:17][C:16]1[C:15]2[C:10](=[CH:11][C:12]([O:33][CH3:34])=[C:13]([O:31][CH3:32])[CH:14]=2)[C:9]([CH2:35][CH2:36][CH3:37])=[N:8][C:7]=1[NH2:41]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 77922tert-Butyl carbamateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86669827HCID 86669827, compound

Product 1

HCID 60164039HCID 60164039, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
140 °C

Procedure

A 2 mL microwave vial equipped with a magnetic stirrer was charged under N2 with 4-(dibenzo[b,d]furan-2-ylmethyl)-6,7-dimethoxy-1-propylisoquinolin-3-yl trifluoromethanesulfonate CCH 42040-1 (13 mg, 23 μmol), t-butyl carbamate (5 mg, 43 μmol), dry powdered cesium carbonate (15 mg, 46 μmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (4 mg, 7 μmol) and tris(dibenzylideneacetone)dipalladium(0) (4 mg, 4 μmol). Dry THF (1.5 mL) was then added and the mixture was stirred for 45 min at 140° C. under microwave irradiation. After cooling to RT, the mixture was diluted with EtOAc (30 mL), then filtered through celite. The solution was washed with brine (10 mL), dried over Na2SO4, filtered and concentrated at 40° C. under vacuum. The residue was then dissolved in CH2Cl2 (10 mL) in a 25 mL round-bottomed flask equipped with a magnetic stirrer before addition of TFA (1 mL) and the mixture was stirred overnight at RT then concentrated to dryness under vacuum. The residue was basified with a saturated NaHCO3 solution (10 mL) before extraction with CH2Cl2 (40 mL). The organic phase was isolated, washed with brine (10 mL), dried over Na2SO4, filtered and concentrated at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent cyclohexane:EtOAc=100:0 to 50:50) gave 4 mg of 4-(dibenzo[b,d]furan-2-ylmethyl)-6,7-dimethoxy-1-propylisoquinolin-3-amine. This free base was dissolved in MeOH (2 mL) in a 10 mL round-bottomed flask equipped with a magnetic stirrer before addition of a 0.49 M HCl solution in MeOH (0.5 mL) and the solution was stirred for 5 min at RT, and concentrated at 40° C. under vacuum to afford 4-(dibenzo[b,d]furan-2-ylmethyl)-6,7-dimethoxy-1-propylisoquinolin-3-amine hydrochloride 65 as a pale brown solid (4 mg, 38% yield).

Workup

  1. customA 2 mL microwave vial equipped with a magnetic stirrer
  2. temperatureAfter cooling to RT
  3. filtrationfiltered through celite
  4. washThe solution was washed with brine (10 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated at 40° C. under vacuum
  8. dissolutionThe residue was then dissolved in CH2Cl2 (10 mL) in a 25 mL round-bottomed flask
  9. customequipped with a magnetic stirrer before addition of TFA (1 mL)
  10. stirringthe mixture was stirred overnight at RT
  11. concentrationthen concentrated to dryness under vacuum
  12. extractionThe residue was basified with a saturated NaHCO3 solution (10 mL) before extraction with CH2Cl2 (40 mL)
  13. customThe organic phase was isolated
  14. washwashed with brine (10 mL)
  15. dry with materialdried over Na2SO4
  16. filtrationfiltered
  17. concentrationconcentrated at 40° C. under vacuum
  18. customPurification by column chromatography (SiO2, eluent cyclohexane:EtOAc=100:0 to 50:50)

Sources & evidence

ORD record
ord-af5ff1393c7f4a14bfc08d279155c2fd
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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