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 409449ノート

反応式

HRID 409449 の反応式
[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]

参加物

9

反応物 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

生成物 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

試薬・触媒・溶媒 4

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 80711,2-Dimethoxyethane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-913ae3525efd448aa0e5bfd4a922d125
出典データセット
uspto-grants-2014_06
特許番号
US08759365B2

反応ノート

読み込み中…