4-Methylmorpholine → (R)-2-hydroxy-1-(3-((2-(2-(1-hydroxyethyl)-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)azetidin-1-yl)-2-methylpropan-1-one

HRID 1923388Notes

Reaction equation

HRID 1923388 reaction equation
[NH:1]1[CH2:4][CH:3]([CH2:5][C:6]2[N:7]([CH3:33])[C:8]3[C:13]([N:14]=2)=[C:12]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[N:11]=[C:10]([N:21]2[C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=4[N:23]=[C:22]2[C@H:30]([OH:32])[CH3:31])[N:9]=3)[CH2:2]1.[OH:34][C:35]([CH3:40])([CH3:39])[C:36](O)=[O:37].C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.CCN=C=NCCCN(C)C>C(Cl)Cl>[OH:34][C:35]([CH3:40])([CH3:39])[C:36]([N:1]1[CH2:4][CH:3]([CH2:5][C:6]2[N:7]([CH3:33])[C:8]3[C:13]([N:14]=2)=[C:12]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[N:11]=[C:10]([N:21]2[C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=4[N:23]=[C:22]2[C@H:30]([OH:32])[CH3:31])[N:9]=3)[CH2:2]1)=[O:37]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 116712-Hydroxyisobutyric acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 59605884(R)-1-[1-(8-Azetidin-3-ylmethyl-9-methyl-6-morpholin-4-yl-9H-purin-2-yl)-1H-benzoimidazol-2-yl]ethanol

Product 1

HCID 59605719(R)-2-hydroxy-1-(3-((2-(2-(1-hydroxyethyl)-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)azetidin-1-yl)-2-methylpropan-1-oneYield 21%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-1-[1-(8-azetidin-3-ylmethyl-9-methyl-6-morpholin-4-yl-9H-purin-2-yl)-1H-benzoimidazol-2-yl]ethanol (57 mg, 0.13 mmol) in DCM (2 mL) was added 2-hydroxy-2-methyl-propionic acid (15 mg, 0.14 mmol), HOBt (19 mg, 0.14 mmol), NMM (31 μL, 0.28 mmol) and EDCI (27 mg, 0.14 mmol) and the resulting mixture stirred at r.t. for 1 h. The reaction mixture was partitioned between DCM and H2O, the organic phase dried (phase separator) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, MeOH:DCM, 0-10%) affording 861 (14 mg, 21%). LCMS (method I): RT 3.05 min, [M+H]+ 535.3. 1H NMR (DMSO, 400 MHz): δ 7.97-7.94 (1H, m), 7.71-7.68 (1 H, m), 7.30-7.26 (2 H, m), 5.58-5.57 (1 H, m), 5.39 (1 H, d, J=6.33 Hz), 5.02 (1H, s), 4.57-4.56 (1 H, m), 4.39-4.14 (4 H, brd s), 4.18 (1 H, dd, J=10.39, 5.70 Hz), 4.04-4.02 (1 H, m), 3.80-3.75 (4 H, m), 3.72 (3 H, s), 3.68 (1 H, dd, J=9.67, 5.21 Hz), 3.23-3.20 (2 H, m), 1.60 (3 H, d, J=6.48 Hz), 1.25 (6 H, s)

Workup

  1. customThe reaction mixture was partitioned between DCM and H2O
  2. customthe organic phase dried (phase separator)
  3. concentrationconcentrated in vacuo
  4. customThe resulting residue was purified by column chromatography (Si-PCC, MeOH:DCM, 0-10%)

Sources & evidence

ORD record
ord-7641c94907a742fdb22bd4eeaaa5f33d
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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