Sodium Carbonate → Cyclopropyl-[5''-(1,2,3,4-tetrahydro-isoquinolin-6-yl)-[2,2';4',3'']terpyridin-6'-yl]-amine

HRID 1798514Notes

Reaction equation

HRID 1798514 reaction equation
C(OC([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13](B3OC(C)(C)C(C)(C)O3)[CH:14]=2)[CH2:9]1)=O)(C)(C)C.C([O-])([O-])=O.[Na+].[Na+].Br[C:34]1[CH:35]=[C:36]([C:40]2[CH:45]=[C:44]([NH:46][CH:47]3[CH2:49][CH2:48]3)[N:43]=[C:42]([C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][N:51]=3)[CH:41]=2)[CH:37]=[N:38][CH:39]=1>COCCOC.C(Cl)Cl>[CH:47]1([NH:46][C:44]2[N:43]=[C:42]([C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][N:51]=3)[CH:41]=[C:40]([C:36]3[CH:37]=[N:38][CH:39]=[C:34]([C:13]4[CH:14]=[C:15]5[C:10](=[CH:11][CH:12]=4)[CH2:9][NH:8][CH2:17][CH2:16]5)[CH:35]=3)[CH:45]=2)[CH2:49][CH2:48]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 44135953(5''-Bromo-[2,2';4',3'']terpyridin-6'-yl)-cyclopropyl-amineHCID 52987621(2-(Tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinolin-6-YL)boronic acid pinacol ester

Product 1

HCID 68760449Cyclopropyl-[5''-(1,2,3,4-tetrahydro-isoquinolin-6-yl)-[2,2';4',3'']terpyridin-6'-yl]-amine

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of 6-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butylester (Intermediate B26) (3 eq, 0.960 mmol, 0.344 g) in dry DME (1 ml) under an inert atmosphere of argon is added 2M Na2CO3 (2 eq, 0.640 mmol, 0.32 ml) followed by (5″-Bromo-[2,2′;4′,3″]terpyridin-6′-yl)-cyclopropyl-amine (Example 1.26) (1 eq, 0.320 mmol, 100 mg) and PdCl2dppf (0.1 eq, 0.032 mmol, 23 mg). The reaction mixture is heated using microwave radiation at 90° C. for 2 hours. The reaction mixture is dissolved in DCM and washed with water. The organic solvent is reduced in vacuo and the residue is purified by reverse phase column chromatography (Isolute™ C18, 0-40% acetonitrile in water—0.1% TFA). The appropriate fractions by HPLC are combined and concentrated in vacuo. The resulting residue is dissolved in MeOH and loaded onto a SCX-2 cartridge eluting with MeOH followed by 2M NH3 in MeOH. The methanolic ammonia fractions are combined, concentrated in vacuo and dried under vacuum to afford the title compound; [M+H]+ 420.

Workup

  1. temperatureThe reaction mixture is heated
  2. customat 90° C.
  3. customfor 2 hours
  4. washwashed with water
  5. customthe residue is purified by reverse phase column chromatography (Isolute™ C18, 0-40% acetonitrile in water—0.1% TFA)
  6. concentrationconcentrated in vacuo
  7. dissolutionThe resulting residue is dissolved in MeOH
  8. washeluting with MeOH
  9. concentrationconcentrated in vacuo
  10. customdried under vacuum

Sources & evidence

ORD record
ord-5b00141d469b4fa0b3af2561b07f2370
Source dataset
uspto-grants-2013_01
Patent number
US08343966B2

Reaction notes

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