Aluminium lithium hydride → HCID 57861320, compound

HRID 1803923Notes

Reaction equation

HRID 1803923 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[C:13]([NH:15][CH2:16][C@@H:17]3[CH2:21][CH2:20][CH2:19][N:18]3[C:22](OC(C)(C)C)=O)[CH:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[C:13]([NH:15][CH2:16][C@@H:17]3[CH2:21][CH2:20][CH2:19][N:18]3[CH3:22])[CH:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 57861318HCID 57861318, compound

Product 1

HCID 57861320HCID 57861320, compoundYield 17.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl (2S)-2-[({2-[(3-chlorophenyl)amino]pyrimidin-4-yl}amino)methyl]pyrrolidine-1-carboxylate (160 mg, 0.40 mmol) in THF (3 mL) is added lithium aluminum hydride (2 M in THF, 0.6 mL, 1.19 mmol). The reaction is stirred at room temperature for 24 hours and then quenched with NaOH (1 N, 2 mL) and stirred for an additional hour. The reaction solution is partitioned between EtOAc and sat. NaHCO3. The organic layer is dried (MgSO4), concentrated in vacuo, and purified over silica (MeOH/CH2Cl2) to afford 22 mg (17% yield) of the desired compound: 1H NMR (CDCl3, 300 MHz) δ 1.58-1.68 (m, 1H), 1.70-1.83 (m, 2H), 1.99-2.11 (m, 1H), 2.29 (q, J=8.7 Hz, 1H), 2.43 (s, 3H), 2.48-2.58 (m, 1H), 3.04-3.12 (m, 1H), 3.29 (t, J=6.3 Hz, 1H), 3.77 (d, J=11.7 Hz, 1H), 6.01 (d, J=6.0 Hz, 1H), 6.94 (ddd, J=8.1, 2.4, 0.9 Hz, 1H), 7.23 (t, J=7.8 Hz, 1H), 7.49 (ddd, J=8.4, 2.1, 0.9 Hz, 1H), 7.78 (d, J=6.0 Hz, 1H), 7.89 (t, J=2.1 Hz, 1H); HRMS calcd for C16H20ClN5, 318.1485 m/z (M+H)+; observed 318.1491 m/z.

Workup

  1. customquenched with NaOH (1 N, 2 mL)
  2. stirringstirred for an additional hour
  3. customThe reaction solution is partitioned between EtOAc and sat. NaHCO3
  4. dry with materialThe organic layer is dried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. custompurified over silica (MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-0055b97f43624d34a18b1745c464d693
Source dataset
uspto-grants-2013_01
Patent number
US08354407B2

Reaction notes

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