Pyrrolidine → HCID 86610556, compound

HRID 506334Notes

Reaction equation

HRID 506334 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][C:12]([O:16][CH3:17])=[CH:13][CH:14]=2)[C@@H:9]([NH:18][C:19]2[N:24]=[C:23]([CH2:25][C:26]3[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[C:28]([C:36]([F:39])([F:38])[F:37])[CH:27]=3)[C:22](Br)=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:41][CH3:42])=[O:5])[CH3:2].CC(C)([O-])C.[Na+].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.[NH:70]1[CH2:74][CH2:73][CH2:72][CH2:71]1>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CCOCC>[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][C:12]([O:16][CH3:17])=[CH:13][CH:14]=2)[C@@H:9]([NH:18][C:19]2[N:24]=[C:23]([CH2:25][C:26]3[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[C:28]([C:36]([F:39])([F:38])[F:37])[CH:27]=3)[C:22]([N:70]3[CH2:74][CH2:73][CH2:72][CH2:71]3)=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:41][CH3:42])=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 31268PyrrolidineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 86610549HCID 86610549, compound

Product 1

HCID 86610556HCID 86610556, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Procedure

(2R*,4S*)-4-{[3,5-Bis(trifluoromethyl)benzyl]-(5-bromopyrimidin-2-yl)}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (250 mg) is dissolved in toluene (2 ml), and thereto are added tris(dibenzylideneacetone)dipalladium (6.9 mg), sodium tert-butoxide (54.8 mg), 2-(di-tert-butylphosphino)biphenyl (9.0 mg) and pyrrolidine (47 μl). The mixture is stirred at room temperature for 45 minutes under nitrogen flow, then heated to 80° C, and stirred for 18 hours. After cooling to room temperature, ether is added to the reaction solution. The mixture is filtered, and the filtrate is concentrated under reduced pressure. The resulting residue is purified by column chromatography (silica gel; hexane:ethyl acetate=9:1→7:3) to give (2R*,4S*)-4-{[3,5-bis(trifluoromethyl)benzyl]-[5-(pyrrolidin-1-yl)pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (158.5 mg). MS (m/z): 653 [M+H]+.

Workup

  1. temperatureheated to 80° C
  2. stirringstirred for 18 hours
  3. temperatureAfter cooling to room temperature
  4. filtrationThe mixture is filtered
  5. concentrationthe filtrate is concentrated under reduced pressure
  6. customThe resulting residue is purified by column chromatography (silica gel; hexane:ethyl acetate=9:1→7:3)

Sources & evidence

ORD record
ord-9adb87c1bd734348813b188fdfe72a7f
Source dataset
uspto-grants-2010_08
Patent number
US07781443B2

Reaction notes

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