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 409449노트

반응식

HRID 409449 반응식
[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]

참가 물질

9

반응물 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

생성물 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

시약·촉매·용매 4

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 6344Dichloromethane용매HCID 80711,2-Dimethoxyethane용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-913ae3525efd448aa0e5bfd4a922d125
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759365B2

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