4-Methylmorpholine → HCID 59605271, compound

HRID 1923389Notes

Reaction equation

HRID 1923389 reaction equation
Cl.[CH2:2]([C:4]1[N:8]([C:9]2[N:17]=[C:16]3[C:12]([N:13]=[C:14]([CH2:19][CH:20]4[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]4)[N:15]3[CH3:18])=[C:11]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)[N:10]=2)[C:7]2[CH:32]=[CH:33][CH:34]=[CH:35][C:6]=2[N:5]=1)[CH3:3].[C:36]([O-])(=[O:40])[C@H:37]([CH3:39])[OH:38].[Na+].C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.CCN=C=NCCCN(C)C>C1COCC1>[CH2:2]([C:4]1[N:8]([C:9]2[N:17]=[C:16]3[C:12]([N:13]=[C:14]([CH2:19][CH:20]4[CH2:21][CH2:22][N:23]([C:36](=[O:40])[C@@H:37]([OH:38])[CH3:39])[CH2:24][CH2:25]4)[N:15]3[CH3:18])=[C:11]([N:26]3[CH2:27][CH2:28][O:29][CH2:30][CH2:31]3)[N:10]=2)[C:7]2[CH:32]=[CH:33][CH:34]=[CH:35][C:6]=2[N:5]=1)[CH3:3]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 23664767Sodium Lactate, L-HCID 67492647HCID 67492647, compound

Product 1

HCID 59605271HCID 59605271, compoundYield 112.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-8-piperidin-4-ylmethyl-9H-purine hydrochloride (13 mg, 0.02 mmol), sodium L-lactate (5 mg, 0.04 mmol) and HOBt (4 mg, 0.03 mmol) in THF (1 mL) was added NMM (5 μL, 0.05 mmol) and EDCI (8 mg, 0.04 mmol) and the resulting mixture was stirred at r.t. for 1 h. The reaction mixture was partitioned between EtOAc and H2O, the organic layer washed with brine, dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, 2M NH3/MeOH:DCM, 0-10%) affording 862 (12 mg, 92%). LCMS (method I): RT 3.18 min, [M+H]+ 533.3. 1H NMR (MeOD, 400 MHz): δ 8.00-7.96 (1 H, m), 7.65-7.61 (1 H, m), 7.28-7.27 (2 H, m), 4.56-4.54 (2 H, m), 4.33 (4 H, brd s), 4.04-4.04 (1 H, m), 3.84 (4 H, t, J=4.75 Hz), 3.79 (3 H, s), 3.17-3.04 (2 H, m), 2.92-2.86 (2H, m), 2.76-2.64 (1 H, m), 2.28-2.25 (1 H, m), 1.92-1.82 (2 H, m), 1.38 (3 H, t, J=7.51 Hz), 1.36-1.26 (6 H, m)

Workup

  1. customThe reaction mixture was partitioned between EtOAc and H2O
  2. washthe organic layer washed with brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified by column chromatography (Si-PCC, 2M NH3/MeOH:DCM, 0-10%)

Sources & evidence

ORD record
ord-c41cbe3773da42609f60d3a6e716d538
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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