Sodium hydride → HCID 66832542, compound

HRID 2044064Notes

Reaction equation

HRID 2044064 reaction equation
Cl[CH2:2][CH2:3][NH:4][C:5](=[O:37])[NH:6][C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13]2[CH:21]=[CH:20][C:16]([C:17]([NH2:19])=[O:18])=[C:15]([NH:22][C:23]3[CH:28]=[CH:27][C:26]([C:29]([N:31]4[CH2:36][CH2:35][O:34][CH2:33][CH2:32]4)=[O:30])=[CH:25][CH:24]=3)[N:14]=2)[CH2:8]1.[H-].[Na+]>CN(C=O)C>[N:31]1([C:29]([C:26]2[CH:27]=[CH:28][C:23]([NH:22][C:15]3[N:14]=[C:13]([N:9]4[CH2:10][CH2:11][CH2:12][C@@H:7]([N:6]5[CH2:2][CH2:3][NH:4][C:5]5=[O:37])[CH2:8]4)[CH:21]=[CH:20][C:16]=3[C:17]([NH2:19])=[O:18])=[CH:24][CH:25]=2)=[O:30])[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 66832992HCID 66832992, compound

Product 1

HCID 66832542HCID 66832542, compoundYield 16.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (R)-6-(3-(3-(2-chloroethyl)ureido)piperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide (86 mg, 0.162 mmol) in DMF (1 mL) was added NaH (32.4 mg, 0.811 mmol) and stirred at rt for 1 h. The reaction mixture was quenched with water, extracted twice into CH2Cl2 twice. The combined organic extracts were washed with 10% LiCl and concentrated. The residue was purified by MPLC chromatography (ISCO, 6% NH4OH/MeOH/CH2Cl2, 40 g silica gel column) and further purified by HPLC. The product containing fractions were collected, basified with 1N NaOH, and extracted with CH2Cl2 twice. The combined organic layers were concentrated to give 13 mg of (R)-2-(4-(morpholine-4-carbonyl)phenylamino)-6-(3-(2-oxoimidazolidin-1-yl)piperidin-1-yl)nicotinamide as a light yellow solid. LCMS: (M+H)+=494.23. 1H NMR (400 MHz, CDCl3) δ ppm 11.17 (1H, s), 7.66-7.71 (2H, m), 7.52 (1H, d, J=8.79 Hz), 7.34-7.39 (2H, m), 6.07 (1H, d, J=8.79 Hz), 5.62-5.84 (2H, m), 4.54 (1H, s), 4.26-4.38 (2H, m), 3.76-3.88 (2H, m), 3.57-3.75 (8H, m), 3.43 (4H, d, J=4.39 Hz), 2.94-3.03 (1H, m), 1.92-2.02 (1H, m), 1.80-1.89 (1H, m), 1.68 (2H, m).

Workup

  1. customThe reaction mixture was quenched with water
  2. extractionextracted twice into CH2Cl2 twice
  3. washThe combined organic extracts were washed with 10% LiCl
  4. concentrationconcentrated
  5. customThe residue was purified by MPLC chromatography (ISCO, 6% NH4OH/MeOH/CH2Cl2, 40 g silica gel column)
  6. customfurther purified by HPLC
  7. additionThe product containing fractions
  8. customwere collected
  9. extractionextracted with CH2Cl2 twice
  10. concentrationThe combined organic layers were concentrated

Sources & evidence

ORD record
ord-4977842492094e45b989ebb9c89c126b
Source dataset
uspto-grants-2013_11
Patent number
US08586751B2

Reaction notes

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