Dimethylformamide → Rac-cis-tert-butyl 4-(2-{2-[(6-cyano-2-methylpyrimidin-4-yl)(4-methoxybenzyl)amino]ethyl}cyclopropyl)piperidine-1-carboxylate

HRID 1039050Notes

Reaction equation

HRID 1039050 reaction equation
I[CH2:2][CH2:3][C@H:4]1[CH2:6][C@H:5]1[CH:7]1[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]1.[OH:20][C:21]1[CH:37]=[CH:36][C:24]([CH2:25][NH:26][C:27]2[N:32]=[C:31]([CH3:33])[N:30]=[C:29]([C:34]#[N:35])[CH:28]=2)=[CH:23][CH:22]=1.[H-].[Na+].[CH3:40]N(C=O)C>>[C:34]([C:29]1[N:30]=[C:31]([CH3:33])[N:32]=[C:27]([N:26]([CH2:25][C:24]2[CH:23]=[CH:22][C:21]([O:20][CH3:40])=[CH:37][CH:36]=2)[CH2:2][CH2:3][C@H:4]2[CH2:6][C@H:5]2[CH:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]2)[CH:28]=1)#[N:35]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 669271566-[(4-Hydroxybenzyl)amino]-2-methylpyrimidine-4-carbonitrileHCID 67778116Rac-cis-tert-butyl 4-[2-(2-iodoethyl)cyclopropyl]piperidine-1-carboxylate

Product 1

HCID 67776889Rac-cis-tert-butyl 4-(2-{2-[(6-cyano-2-methylpyrimidin-4-yl)(4-methoxybenzyl)amino]ethyl}cyclopropyl)piperidine-1-carboxylate

Procedure

Rac-cis-tert-butyl 4-[2-(2-iodoethyl)cyclopropyl]piperidine-1-carboxylate (86 mg, 0.23 mmol) from Step 3 of this example and 6-[(4-hydroxybenzyl)amino]-2-methylpyrimidine-4-carbonitrile (63.4 mg, 0.25 mmol) from Step 2 of this example were dissolved in DMF (2.3 mL), sodium hydride (18 mg, 0.45 mmol) was added. After 10 minutes, the reaction was quenched with saturated ammonia chloride solution (5 mL), extracted with ethyl acetate (10 mL), second washed with brine (5 mL). The organic phase was dried by magnesium sulfate, filtered, concentrated and purified by preparative-TLC (Analtech Silica Gel GF 1500 μM, 20×20 cm) using 30% ethyl acetate/hexane to give the title compound as a white solid.

Workup

  1. customthe reaction was quenched with saturated ammonia chloride solution (5 mL)
  2. extractionextracted with ethyl acetate (10 mL)
  3. washsecond washed with brine (5 mL)
  4. dry with materialThe organic phase was dried by magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by preparative-TLC (Analtech Silica Gel GF 1500 μM, 20×20 cm)

Sources & evidence

ORD record
ord-71173aacc13d495db7d2958e92b42851
Source dataset
uspto-grants-2013_10
Patent number
US08552022B2

Reaction notes

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