Aluminium lithium hydride → HCID 57861323, compound

HRID 1803926Notes

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][N:19]([C:22](OC(C)(C)C)=O)[CH2:18]3)[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][N:19]([CH3:22])[CH2:18]3)[CH:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of tert-butyl (3S)-3-[({2-[(3-chlorophenyl)-amino]pyrimidin-4-yl}amino)methyl]pyrrolidine-1-carboxylate, 19, (356 mg, 0.88 mmol) in THF (2 mL) is added lithium aluminum hydride (2 M in THF, 1.32 mL, 2.64 mmol). The reaction is heated to 50° C. for 3 days, cooled to room temperature, quenched with NaOH (1 N, 2 mL) and stirred for an additional hour. The reaction mixture is extracted with EtOAc (2×25 mL) and the combined organic layers are dried (MgSO4), concentrated in vacuo, and purified over silica (MeOH/CH2Cl2) to afford 190 mg (68% yield) of the desired product: 1H NMR (DMSO, 300 MHz) δ 1.40-1.50 (m, 1H), 1.86-1.96 (m, 1H), 2.23 (s, 3H), 2.25-2.33 (m, 1H), 2.34-2.41 (m, 1H), 2.42-2.54 (m, 5H), 5.96 (d, J=5.7 Hz, 1H), 6.89 (dt, J=7.5, 0.9 Hz, 1H), 7.22 (t, J=8.4 Hz, 1H), 7.39 (bs, 1H), 7.57 (d, J=7.8 Hz, 1H), 7.74-7.85 (m, 2H), 8.15 (bs, 1H), 9.21 (s, 1H); HRMS calcd for C16H20ClN5, 318.1485 m/z (M+H)+; observed 318.1485 m/z.

Workup

temperaturecooled to room temperature
customquenched with NaOH (1 N, 2 mL)
extractionThe reaction mixture is extracted with EtOAc (2×25 mL)
dry with materialthe combined organic layers are dried (MgSO4)
concentrationconcentrated in vacuo
custompurified over silica (MeOH/CH2Cl2)

Sources & evidence

ORD record: ord-1cbf995e9537471ca3bc80423f67c0aa
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08354407B2

Reaction notes

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