Dimethylformamide → 2-((R)-1-(4-hydroxycyclohexyl)ethylamino)-4-(1-tosyl-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidine-5-carbonitrile

HRID 1853464Notes

Reaction equation

HRID 1853464 reaction equation
[NH2:1][C@@H:2]([CH:4]1[CH2:9][CH2:8][CH:7]([OH:10])[CH2:6][CH2:5]1)[CH3:3].CN(C=O)C.C(N(C(C)C)CC)(C)C.Cl[C:26]1[N:31]=[C:30]([C:32]2[C:40]3[C:35](=[N:36][CH:37]=[C:38]([C:41]([F:44])([F:43])[F:42])[CH:39]=3)[N:34]([S:45]([C:48]3[CH:54]=[CH:53][C:51]([CH3:52])=[CH:50][CH:49]=3)(=[O:47])=[O:46])[CH:33]=2)[C:29]([C:55]#[N:56])=[CH:28][N:27]=1>C1COCC1>[OH:10][CH:7]1[CH2:8][CH2:9][CH:4]([C@H:2]([NH:1][C:26]2[N:31]=[C:30]([C:32]3[C:40]4[C:35](=[N:36][CH:37]=[C:38]([C:41]([F:43])([F:44])[F:42])[CH:39]=4)[N:34]([S:45]([C:48]4[CH:54]=[CH:53][C:51]([CH3:52])=[CH:50][CH:49]=4)(=[O:46])=[O:47])[CH:33]=3)[C:29]([C:55]#[N:56])=[CH:28][N:27]=2)[CH3:3])[CH2:5][CH2:6]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 55285649(R)-4-(1-Aminoethyl)cyclohexan-1-olHCID 594144402-chloro-4-(1-tosyl-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidine-5-carbonitrile

Product 1

HCID 594144152-((R)-1-(4-hydroxycyclohexyl)ethylamino)-4-(1-tosyl-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidine-5-carbonitrileYield 88.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-((R)-1-aminoethyl)cyclohexanol (309.4 mg, 2.16 mmol) was dissolved in THF (10 mL) and DMF (4 mL) and stirred over molecular sieves for 10 minutes. Diisopropylethylamine (376.3 μL, 2.160 mmol) was added, followed by 2-chloro-4-(1-tosyl-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidine-5-carbonitrile (516.1 mg, 1.080 mmol). The reaction mixture was stirred under nitrogen at ambient temperature for 18 hours. The molecular sieves was removed by filtration and washed with EtOAc. The filtrate was washed with water, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified on silica gel by flash column chromatography (ISCO Companion|, 80 g column, 0-100% EtOAc/DCM) to afford the title compound as a yellow solid (558 mg, 88% yield).

Workup

  1. customThe molecular sieves was removed by filtration
  2. washwashed with EtOAc
  3. washThe filtrate was washed with water
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified on silica gel by flash column chromatography (ISCO Companion|, 80 g column, 0-100% EtOAc/DCM)

Sources & evidence

ORD record
ord-de7aa8010bf844dcb8829b9217c9ae44
Source dataset
uspto-grants-2015_02
Patent number
US08962642B2

Reaction notes

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