Lithium Hexamethyldisilazide → 1-(4'-(Cyclopropylmethyl)-2-(4-(methylsulfonyl)phenylamino)-4,5'-bipyrimidin-2'-ylamino)-2-methylpropan-2-ol

HRID 2359746Notes

Reaction equation

HRID 2359746 reaction equation
[S:1](=[C:4]1[CH:10]=[CH:9][C:7]([NH2:8])=[CH:6][CH2:5]1)(=[O:3])=[O:2].[Li+].[CH3:12][Si]([N-][Si](C)(C)C)(C)C.[CH:21]1([CH2:24][C:25]2[C:30]([C:31]3[CH:36]=[CH:35][N:34]=[C:33](S(C)=O)[N:32]=3)=[CH:29][N:28]=[C:27]([NH:40][CH2:41][C:42]([CH3:45])([OH:44])[CH3:43])[N:26]=2)[CH2:23][CH2:22]1>C1COCC1>[CH:21]1([CH2:24][C:25]2[C:30]([C:31]3[CH:36]=[CH:35][N:34]=[C:33]([NH:8][C:7]4[CH:6]=[CH:5][C:4]([S:1]([CH3:12])(=[O:3])=[O:2])=[CH:10][CH:9]=4)[N:32]=3)=[CH:29][N:28]=[C:27]([NH:40][CH2:41][C:42]([CH3:45])([OH:44])[CH3:43])[N:26]=2)[CH2:22][CH2:23]1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 204326224-SulfonylanilineHCID 679836401-(4'-(Cyclopropylmethyl)-2-(methylsulfinyl)-4,5'-bipyrimidin-2'-ylamino)-2-methylpropan-2-ol

Product 1

HCID 679839941-(4'-(Cyclopropylmethyl)-2-(4-(methylsulfonyl)phenylamino)-4,5'-bipyrimidin-2'-ylamino)-2-methylpropan-2-olYield 17%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-sulfonylaniline (71.1 mg, 0.415 mmol) in THF (277 μl) cooled to −78° C. under nitrogen, LiHMDS (69.4 mg, 0.415 mmol) was added dropwise. The reaction mixture was warmed up to rt, then was stirred for 30 min. To the reaction mixture cooled back to −78° C., 1-(4′-(cyclopropylmethyl)-2-(methylsulfinyl)-4,5′-bipyrimidin-2′-ylamino)-2-methylpropan-2-ol (5-3) (50 mg, 0.138 mmol) was added, and the reaction mixture was warmed up to rt, then was stirred for additional 1 h. According to LC/MS, the reaction was complete. The crude product was purified by reverse-phase HPLC [30-100% organic phase over 15 min] followed by Biotage silica gel chromatography [10 g SNAP column, 100% DCM to 12% MeOH/DCM] to obtain the desired product (11 mg, 17%).

Workup

  1. temperatureTo the reaction mixture cooled back to −78° C.
  2. temperaturethe reaction mixture was warmed up to rt
  3. stirringwas stirred for additional 1 h
  4. customThe crude product was purified by reverse-phase HPLC [30-100% organic phase over 15 min]

Sources & evidence

ORD record
ord-118d3a09845d435d89e8dd4ee1074124
Source dataset
uspto-grants-2014_04
Patent number
US08685993B2

Reaction notes

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