4-Methylmorpholine → HCID 59606014, compound

HRID 1923364Notes

Reaction equation

HRID 1923364 reaction equation
[OH:1][C:2]([CH3:7])([CH3:6])[C:3](O)=[O:4].[CH2:8]([C:10]1[N:14]([C:15]2[N:23]=[C:22]3[C:18]([N:19]=[C:20]([C:25]4([O:31][CH3:32])[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]4)[N:21]3[CH3:24])=[C:17]([N:33]3[CH2:38][CH2:37][O:36][CH2:35][CH2:34]3)[N:16]=2)[C:13]2[CH:39]=[CH:40][CH:41]=[CH:42][C:12]=2[N:11]=1)[CH3:9].C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.CCN=C=NCCCN(C)C>C1COCC1>[CH2:8]([C:10]1[N:14]([C:15]2[N:23]=[C:22]3[C:18]([N:19]=[C:20]([C:25]4([O:31][CH3:32])[CH2:30][CH2:29][N:28]([C:3](=[O:4])[C:2]([OH:1])([CH3:7])[CH3:6])[CH2:27][CH2:26]4)[N:21]3[CH3:24])=[C:17]([N:33]3[CH2:34][CH2:35][O:36][CH2:37][CH2:38]3)[N:16]=2)[C:13]2[CH:39]=[CH:40][CH:41]=[CH:42][C:12]=2[N:11]=1)[CH3:9]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 116712-Hydroxyisobutyric acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 59605917HCID 59605917, compound

Product 1

HCID 59606014HCID 59606014, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-hydroxyisobutyric acid (49 mg, 0.47 mmol) in THF (3 mL) was added 2-(2-ethylbenzoimidazol-1-yl)-8-(4-methoxypiperidin-4-yl)-9-methyl-6-morpholin-4-yl-9H-purine (150 mg, 0.32 mmol), HOBt (47 mg, 0.35 mmol), NMM (77 μL, 0.69 mmol) and EDCI (91 mg, 0.47 mmol). The resulting mixture was allowed to stir at r.t. for 4 h then quenched with sat. aq. NH4Cl and extracted with DCM. The organic phase was washed with brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, MeOH:EtOAc, 0-20%) then triturated with MeOH/H2O. The resulting solid was collected by filtration and dried in vacuo affording 800 (111 mg, 63%). LCMS (method G): RT 7.36 min, [M+H]+ 563.4. 1H NMR (DMSO, 400 MHz): δ 8.05-8.04 (1 H, m), 7.66-7.62 (1 H, m), 7.25-7.24 (2 H, m), 5.44 (1 H, s), 4.26 (6 H, brd s), 3.92 (3 H, s), 3.78 (4 H, t, J=4.52 Hz), 3.30-3.23 (4 H, m), 3.09 (3 H, s), 2.26-2.16 (2 H, m), 2.19-2.02 (2 H, m), 1.35-1.33 (9 H, m)

Workup

  1. customthen quenched with sat. aq. NH4Cl
  2. extractionextracted with DCM
  3. washThe organic phase was washed with brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by column chromatography (Si-PCC, MeOH:EtOAc, 0-20%)
  7. customthen triturated with MeOH/H2O
  8. filtrationThe resulting solid was collected by filtration
  9. customdried in vacuo

Sources & evidence

ORD record
ord-393dd63612e547ecb062d70a2fdc06c7
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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