Pyrrolidine → HCID 68290211, compound

HRID 878747Notes

Reaction equation

HRID 878747 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH3:12])=[C:4]([N:13]([CH2:28][C:29]2[CH:34]=[CH:33][C:32]([O:35][C:36]([F:39])([F:38])[F:37])=[CH:31][CH:30]=2)[S:14]([C:17]2[CH:27]=[CH:26][C:20]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:19][CH:18]=2)(=[O:16])=[O:15])[N:3]=1.[NH:40]1[CH2:44][CH2:43][CH2:42][CH2:41]1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1>[CH3:12][C:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:2]([N:40]2[CH2:44][CH2:43][CH2:42][CH2:41]2)=[N:3][C:4]=1[N:13]([CH2:28][C:29]1[CH:34]=[CH:33][C:32]([O:35][C:36]([F:38])([F:39])[F:37])=[CH:31][CH:30]=1)[S:14]([C:17]1[CH:27]=[CH:26][C:20]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:19][CH:18]=1)(=[O:15])=[O:16]

Participants

6

Reactant 4

HCID 31268PyrrolidineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 86707383HCID 86707383, compound

Product 1

HCID 68290211HCID 68290211, compoundYield 24.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of ethyl 4-({(1-bromo-4-methylisoquinolin-3-yl)[4-(trifluoromethoxy)-benzyl]amino}sulfonyl)benzoate (93.5 mg, 0.15 mmol) prepared in Example 9-(1), pyrrolidine (0.015 mL, 0.18 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (9.3 mg, 0.015 mmol), trisdibenzylideneacetone dipalladium (6.9 mg, 0.0075 mmol) and sodium-t-butoxide (20.2 mg, 0.21 mmol) in toluene (2 mL) was stirred at 100° C. for 4 hours under argon atmosphere. The mixture was cooled to room temperature, and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate/hexane=10%→25%) to give ethyl 4-({(4-methyl-1-pyrrolidin-1-ylisoquinolin-3-yl) [4-(trifluoromethoxy)benzyl]amino}sulfonyl)benzoate (22.4 mg, 24%) as a yellow viscous material.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. filtrationfiltered
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. customThe resulting residue was purified by silica gel column chromatography (ethyl acetate/hexane=10%→25%)

Sources & evidence

ORD record
ord-c5eeb46deffa412380fd2df6c8d18be3
Source dataset
uspto-grants-2015_03
Patent number
US08987445B2

Reaction notes

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