1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 59605392, compound

HRID 1923378Notes

Reaction equation

HRID 1923378 reaction equation
[CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[C:13]([C:18]4([O:22][CH3:23])[CH2:21][NH:20][CH2:19]4)[N:14]3[CH3:17])=[C:10]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[N:9]=2)[C:6]2[CH:30]=[CH:31][CH:32]=[CH:33][C:5]=2[N:4]=1)[CH3:2].[C:34]([O-])(=[O:38])[C@H:35]([CH3:37])[OH:36].[Na+].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>C(Cl)Cl>[CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[C:13]([C:18]4([O:22][CH3:23])[CH2:21][N:20]([C:34](=[O:38])[C@@H:35]([OH:36])[CH3:37])[CH2:19]4)[N:14]3[CH3:17])=[C:10]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[N:9]=2)[C:6]2[CH:30]=[CH:31][CH:32]=[CH:33][C:5]=2[N:4]=1)[CH3:2]

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 23664767Sodium Lactate, L-HCID 596058342-(2-Ethylbenzoimidazol-1-yl)-8-(3-methoxyazetidin-3-yl)-9-methyl-6-morpholin-4-yl-9H-purine

Product 1

HCID 59605392HCID 59605392, compoundYield 25.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 2-(2-ethylbenzoimidazol-1-yl)-8-(3-methoxyazetidin-3-yl)-9-methyl-6-morpholin-4-yl-9H-purine (100 mg, 0.22 mmol) and sodium L-lactate (38 mg, 0.34 mmol) in DCM (2 mL) was added HOBt (33 mg, 0.25 mmol) and EDCI (64 mg, 0.34 mmol). The resulting mixture was allowed to stir at r.t. for 18 h then partitioned between DCM and sat. aq. NH4Cl. The organic phase was dried (phase separator), concentrated in vacuo and the resulting residue purified by column chromatography (Si-PCC, MeOH:EtOAc, 0-25%). The resulting residue was triturated with Et2O and further purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 0.1% HCO2H in water on a gradient MeOH 45-60%) affording 840 (29 mg, 23%). LCMS (method I): RT 3.10 min, [M+H]+ 521.3. 1H NMR (DMSO, 400 MHz): δ 8.44 (1 H, brd s), 8.07-8.03 (1 H, m), 7.64-7.63 (1 H, m), 7.25-7.24 (2 H, m), 5.24 (1 H, brd s), 4.94 (1 H, dd, J=21.10, 10.14 Hz), 4.59-4.58 (2 H, m), 4.46-4.12 (4 H, brd s), 4.18-4.17 (2 H, m), 3.79 (4 H, t, J=4.51 Hz), 3.72 (3 H, s), 3.34-3.32 (2 H, m), 3.09 (3 H, s), 1.34 (3 H, t, J=7.43 Hz), 1.20 (3 H, d, J=6.71 Hz)

Workup

  1. customthen partitioned between DCM and sat. aq. NH4Cl
  2. customThe organic phase was dried (phase separator)
  3. concentrationconcentrated in vacuo
  4. customthe resulting residue purified by column chromatography (Si-PCC, MeOH:EtOAc, 0-25%)
  5. customThe resulting residue was triturated with Et2O
  6. customfurther purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 0.1% HCO2H in water on a gradient MeOH 45-60%)

Sources & evidence

ORD record
ord-2aa5d7b32a144c80bb78625cfeafdd83
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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