N-methyl-2-pyrrolidone → (4-hydroxy-piperidin-1-yl)-(4-{4-[7-(3-methanesulfonyl-propoxy)-1H-indazol-3-yl]-pyrimidin-2-ylamino}-cyclohexyl)-methanone

HRID 1947016Notes

Reaction equation

HRID 1947016 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][CH:5]([C:8]([N:10]2[CH2:15][CH2:14][CH:13]([OH:16])[CH2:12][CH2:11]2)=[O:9])[CH2:4][CH2:3]1.CCN(C(C)C)C(C)C.CN1C(=O)CCC1.[CH3:33][S:34]([CH2:37][CH2:38][CH2:39][O:40][C:41]1[CH:42]=[CH:43][CH:44]=[C:45]2[C:49]=1[NH:48][N:47]=[C:46]2[C:50]1[CH:55]=[CH:54][N:53]=[C:52](S(C)=O)[N:51]=1)(=[O:36])=[O:35]>O>[OH:16][CH:13]1[CH2:14][CH2:15][N:10]([C:8]([CH:5]2[CH2:4][CH2:3][CH:2]([NH:1][C:52]3[N:51]=[C:50]([C:46]4[C:45]5[C:49](=[C:41]([O:40][CH2:39][CH2:38][CH2:37][S:34]([CH3:33])(=[O:35])=[O:36])[CH:42]=[CH:43][CH:44]=5)[NH:48][N:47]=4)[CH:55]=[CH:54][N:53]=3)[CH2:7][CH2:6]2)=[O:9])[CH2:11][CH2:12]1

Participants

6

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 20754665(4-Amino-cyclohexyl)-(4-hydroxy-piperidin-1-yl)-methanoneHCID 693086167-(3-methanesulfonyl-propoxy)-3-(2-methanesulfinyl-pyrimidin-4-yl)-1H-indazole

Product 1

HCID 59743603(4-hydroxy-piperidin-1-yl)-(4-{4-[7-(3-methanesulfonyl-propoxy)-1H-indazol-3-yl]-pyrimidin-2-ylamino}-cyclohexyl)-methanone

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of (4-amino-cyclohexyl)-(4-hydroxy-piperidin-1-yl)-methanone (400 mg, 1.5 mmol), DIPEA (0.31 mL, 1.78 mmol) and NMP (1 mL) was stirred at RT for 1 h. Then, 7-(3-methanesulfonyl-propoxy)-3-(2-methanesulfinyl-pyrimidin-4-yl)-1H-indazole (200 mg, 0.5 mmol) was added to the mixture and stirred at 130° C. for 2.5 hours. The reaction mixture was then poured into water, and the precipitate was purified on a silica column using flash chromatography, eluting with hexane:EtOAc:MeOH 5:4.5:0.5 to yield (4-hydroxy-piperidin-1-yl)-(4-{4-[7-(3-methanesulfonyl-propoxy)-1H-indazol-3-yl]-pyrimidin-2-ylamino}-cyclohexyl)-methanone (Compound 308).

Workup

  1. stirringstirred at 130° C. for 2.5 hours
  2. customthe precipitate was purified on a silica column
  3. washeluting with hexane:EtOAc:MeOH 5:4.5:0.5

Sources & evidence

ORD record
ord-c0a02b8b39df449284d5a44ef587eb47
Source dataset
uspto-grants-2013_03
Patent number
US08399462B2

Reaction notes

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