4-Aminobenzonitrile → 4-(4'-(Cyclopropylmethyl)-2'-(2-hydroxy-2-methylpropylamino)-4,5'-bipyrimidin-2-ylamino)benzonitrile

HRID 1397148Notes

Reaction equation

HRID 1397148 reaction equation
[NH2:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH:20]1([CH2:23][C:24]2[C:29]([C:30]3[CH:35]=[CH:34][N:33]=[C:32](S(C)=O)[N:31]=3)=[CH:28][N:27]=[C:26]([NH:39][CH2:40][C:41]([CH3:44])([OH:43])[CH3:42])[N:25]=2)[CH2:22][CH2:21]1>C1COCC1>[CH:20]1([CH2:23][C:24]2[C:29]([C:30]3[CH:35]=[CH:34][N:33]=[C:32]([NH:1][C:2]4[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=4)[N:31]=3)=[CH:28][N:27]=[C:26]([NH:39][CH2:40][C:41]([OH:43])([CH3:42])[CH3:44])[N:25]=2)[CH2:21][CH2:22]1

Participants

5

Reactant 3

HCID 133964-AminobenzonitrileHCID 2733832Lithium HexamethyldisilazideHCID 679836401-(4'-(Cyclopropylmethyl)-2-(methylsulfinyl)-4,5'-bipyrimidin-2'-ylamino)-2-methylpropan-2-ol

Product 1

HCID 679836894-(4'-(Cyclopropylmethyl)-2'-(2-hydroxy-2-methylpropylamino)-4,5'-bipyrimidin-2-ylamino)benzonitrileYield 28%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-aminobenzonitrile (16.34 mg, 0.138 mmol) in THF (277 μl) cooled to −78° C. under nitrogen, LiHMDS (415 μl, 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 (16 mg, 28%).

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-a9deddbc73ce4b5ead6dea90329d9b95
Source dataset
uspto-grants-2014_12
Patent number
US08901147B2

Reaction notes

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