Triethylamine → 1-(3-((2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)azetidin-1-yl)-2-methylpropan-1-one

HRID 1946179Notes

Reaction equation

HRID 1946179 reaction equation
[NH:1]1[CH2:4][CH:3]([CH2:5][C:6]2[N:7]([CH3:32])[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[CH2:30][CH3:31])[N:9]=3)[CH2:2]1.[C:33](Cl)(=[O:37])[CH:34]([CH3:36])[CH3:35].CCN(CC)CC>C(Cl)Cl>[CH2:30]([C:22]1[N:21]([C:10]2[N:9]=[C:8]3[C:13]([N:14]=[C:6]([CH2:5][CH:3]4[CH2:2][N:1]([C:33](=[O:37])[CH:34]([CH3:36])[CH3:35])[CH2:4]4)[N:7]3[CH3:32])=[C:12]([N:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)[N:11]=2)[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=2[N:23]=1)[CH3:31]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 62325Isobutyryl chlorideHCID 596052818-Azetidin-3-ylmethyl-2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine

Product 1

HCID 596055351-(3-((2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)azetidin-1-yl)-2-methylpropan-1-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 8-azetidin-3-ylmethyl-2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine (121 mg, 0.28 mmol), isobutyryl chloride (30 mg, 0.29 mmol) and NEt3 (50 μL, 0.36 mmol) in DCM (1 mL) was allowed to stir at r.t. for 2 h then concentrated in vacuo. The resulting residue purified by column chromatography (Si—PCC, MeOH:DCM, 0-6%) followed by triturating with Et2O affording 824 as a white solid (86 mg, 61%). LCMS (method I): RT 3.42 min, [M+H]+ 503.2. 1H NMR (CDCl3, 400 MHz): δ 7.99-7.99 (1 H, m), 7.75-7.74 (1 H, m), 7.30-7.22 (2 H, m), 4.50-4.20 (4 H, brd s), 4.41 (1 H, t, J=8.45 Hz), 4.32-4.21 (1 H, m), 3.98 (1 H, dd, J=8.63, 5.41 Hz), 3.90-3.80 (5 H, m), 3.76 (3 H, s), 3.34 (2 H, q, J=7.49 Hz), 3.28-3.25 (1 H, m), 3.16-3.11 (2 H, m), 2.47-2.46 (1 H, m), 1.44 (3 H, t, J=7.48 Hz), 1.12 (6 H, dd, J=6.82, 2.82 Hz)

Workup

  1. concentrationthen concentrated in vacuo
  2. customThe resulting residue purified by column chromatography (Si—PCC, MeOH:DCM, 0-6%)
  3. customby triturating with Et2O affording 824 as a white solid (86 mg, 61%)
  4. customRT 3.42 min, [M+H]+ 503.2

Sources & evidence

ORD record
ord-632570af1c1e4bfb832a3885b94c5ebc
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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