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 1923062ノート

反応式

HRID 1923062 の反応式
[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

参加物

7

反応物 5

HCID 176Acetic AcidHCID 9005Trimethyl orthoformateHCID 5049666Sodium triacetoxyborohydrideHCID 532492042-Azetidin-3-yl-propan-2-olHCID 59605420HCID 59605420、化合物

生成物 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-ol収率 23%

試薬・触媒・溶媒 1

HCID 111,2-Dichloroethane溶媒

実験手順

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)

後処理

  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)

出典と根拠

ORDレコード
ord-8a51235a40a8432fa82d386397b15dd6
出典データセット
uspto-grants-2012_05
特許番号
US08173650B2

反応ノート

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