Acetic Acid → 2-(1-((9-methyl-2-(2-methyl-1H-benzo[d]imidazol-1-yl)-6-morpholino-9H-purin-8-yl)methyl)azetidin-3-yl)propan-2-ol

HRID 1923062Notes

Reaction equation

HRID 1923062 reaction equation
[CH3:1][C:2]1[N:6]([C:7]2[N:15]=[C:14]3[C:10]([N:11]=[C:12]([CH:17]=O)[N:13]3[CH3:16])=[C:9]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)[N:8]=2)[C:5]2[CH:25]=[CH:26][CH:27]=[CH:28][C:4]=2[N:3]=1.[NH:29]1[CH2:32][CH:31]([C:33]([OH:36])([CH3:35])[CH3:34])[CH2:30]1.COC(OC)OC.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH3:16][N:13]1[C:12]([CH2:17][N:29]2[CH2:32][CH:31]([C:33]([OH:36])([CH3:35])[CH3:34])[CH2:30]2)=[N:11][C:10]2[C:14]1=[N:15][C:7]([N:6]1[C:5]3[CH:25]=[CH:26][CH:27]=[CH:28][C:4]=3[N:3]=[C:2]1[CH3:1])=[N:8][C:9]=2[N:19]1[CH2:20][CH2:21][O:22][CH2:23][CH2:24]1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 9005Trimethyl orthoformateHCID 5049666Sodium triacetoxyborohydrideHCID 532492042-Azetidin-3-yl-propan-2-olHCID 59605420HCID 59605420, compound

Product 1

HCID 596057472-(1-((9-methyl-2-(2-methyl-1H-benzo[d]imidazol-1-yl)-6-morpholino-9H-purin-8-yl)methyl)azetidin-3-yl)propan-2-olYield 23%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of 2-(2-methylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (0.075 g, 0.20 mmol), 2-azetidin-3-ylpropan-2-ol (0.023 g, 0.20 mmol) in DCE (2 mL), trimethoxymethane (0.215 mL, 2 mmol) and acetic acid (0.012 mL, 0.2 mmol) was stirred for 1 h at room temperature. Sodium triacetoxyborohydride (0.042 g, 0.2 mmol) was added and the reaction mixture was stirred for 18 h at room temperature. The reaction mixture was partitioned between DCM and water, and the organic layer was separated, washed with brine, dried over sodium sulphate and concentrated. The residue was purified by flash chromatography (Si—PPC, MEOH:DCM, gradient 0:100 to 10:90) to give 315 as an off-white solid (0.020 g, 23%). LCMS (Method G): RT=5.61 min, [M+H]+ 477.2. 1H NMR (CDCl3, 400 MHz) δ 8.11-8.07 (m, 1 H); 7.72-7.69 (m, 1 H); 7.35-7.26 (m, 2 H); 4.42-4.31 (m, 4 H); 3.89-3.82 (m, 11 H); 3.62-3.12 (m, 2 H); 2.94 (s, 3 H); 2.70-2.55 (m, 1H); 1.18 (s, 6 H)

Workup

  1. stirringthe reaction mixture was stirred for 18 h at room temperature
  2. customThe reaction mixture was partitioned between DCM and water
  3. customthe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography (Si—PPC, MEOH:DCM, gradient 0:100 to 10:90)

Sources & evidence

ORD record
ord-8a51235a40a8432fa82d386397b15dd6
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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