Nitrogen → 1-{4-[(2R,4S)-4-((3,5-bis-trifluoromethyl-benzyl)-{5-[1-(tetrahydro-pyran-2-yl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}amino)-2-ethyl-pyrrolidin-1-yl]-5-chloro-pyrimidin-2-yl}-piperidine-4-carboxylic acid ethyl ester

HRID 409449Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 409449
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[N:7]1[CH:11]=[C:10](B2OC(C)(C)C(C)(C)O2)[CH:9]=[N:8]1.[CH2:21]([O:23][C:24]([CH:26]1[CH2:31][CH2:30][N:29]([C:32]2[N:37]=[C:36]([N:38]3[CH2:42][C@@H:41]([N:43]([CH2:51][C:52]4[CH:57]=[C:56]([C:58]([F:61])([F:60])[F:59])[CH:55]=[C:54]([C:62]([F:65])([F:64])[F:63])[CH:53]=4)[C:44]4[N:49]=[CH:48][C:47](Br)=[CH:46][N:45]=4)[CH2:40][C@H:39]3[CH2:66][CH3:67])[C:35]([Cl:68])=[CH:34][N:33]=2)[CH2:28][CH2:27]1)=[O:25])[CH3:22].N#N.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.ClCCl.O.COCCOC>[CH2:21]([O:23][C:24]([CH:26]1[CH2:31][CH2:30][N:29]([C:32]2[N:37]=[C:36]([N:38]3[CH2:42][C@@H:41]([N:43]([CH2:51][C:52]4[CH:57]=[C:56]([C:58]([F:61])([F:60])[F:59])[CH:55]=[C:54]([C:62]([F:65])([F:63])[F:64])[CH:53]=4)[C:44]4[N:49]=[CH:48][C:47]([C:10]5[CH:9]=[N:8][N:7]([CH:2]6[CH2:3][CH2:4][CH2:5][CH2:6][O:1]6)[CH:11]=5)=[CH:46][N:45]=4)[CH2:40][C@H:39]3[CH2:66][CH3:67])[C:35]([Cl:68])=[CH:34][N:33]=2)[CH2:28][CH2:27]1)=[O:25])[CH3:22]

Komponenten

9

Edukt 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 510003841-(oxan-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 596143621-(4-{(2R,4S)-4-[(3,5-bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-amino]-2-ethyl-pyrrolidin-1-yl}-5-chloro-pyrimidin-2-yl)-piperidine-4-carboxylic acid ethyl ester

Produkt 1

HCID 596143501-{4-[(2R,4S)-4-((3,5-bis-trifluoromethyl-benzyl)-{5-[1-(tetrahydro-pyran-2-yl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}amino)-2-ethyl-pyrrolidin-1-yl]-5-chloro-pyrimidin-2-yl}-piperidine-4-carboxylic acid ethyl ester

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 80711,2-DimethoxyethaneLösungsmittel

Versuchsvorschrift

A 25 ml round-bottom flask is charged with 1-(tetrahydro-pyran-2-yl)-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (83 mg, 0.3 mmol), 1-(4-{(2R,4S)-4-[(3,5-bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-amino]-2-ethyl-pyrrolidin-1-yl}-5-chloro-pyrimidin-2-yl)-piperidine-4-carboxylic acid ethyl ester (178 mg, 0.23 mmol) under N2. Pd(PPh3)4 (57 mg, 0.05 mmol) is added promptly and the flask is recharged with N2. Then DME (1 ml), Na2CO3 (1 M in H2O, 0.45 ml, 0.45 mmol) are added. The mixture is then heated to 95 degree for 2 hrs. After cooling down to rt, NaIO4 (140 mg, 0.72 mmol) is added into reaction mixture. Stirring is continued for 1 h to give white suspension. H2O and dichloromethane are added, and then organic layer is collected. Removal of solvent give 1-{4-[(2R,4S)-4-((3,5-bis-trifluoromethyl-benzyl)-{5-[1-(tetrahydro-pyran-2-yl)-1H-pyrazol-4-yl]pyrimidin-2-yl}-amino)-2-ethyl-pyrrolidin-1-yl]-5-chloro-pyrimidin-2-yl}-piperidine-4-carboxylic acid ethyl ester which is used without further purification.

Aufarbeitung

  1. temperatureThe mixture is then heated to 95 degree for 2 hrs
  2. customto give white suspension
  3. customorganic layer is collected
  4. customRemoval of solvent

Quellen und Nachweise

ORD-Eintrag
ord-913ae3525efd448aa0e5bfd4a922d125
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08759365B2

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