Sodium triacetoxyborohydride → 1-((9-methyl-6-morpholino-8-((4-(oxetan-3-yl)piperidin-1-yl)methyl)-9H-purin-2-yl)-1H-benzo[d]imidazol-2-yl)ethanol

HRID 1946019ノート

反応式

HRID 1946019 の反応式
O[CH2:2][CH2:3][C:4]1[N:8]([C:9]2[N:17]=[C:16]3[C:12]([N:13]=[C:14]([CH:19]=O)[N:15]3[CH3:18])=[C:11]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)[N:10]=2)[C:7]2[CH:27]=[CH:28][CH:29]=[CH:30][C:6]=2[N:5]=1.[O:31]1[CH2:34][CH:33]([CH:35]2[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]2)[CH2:32]1.C(O[BH-](OC(=O)C)OC(=O)C)(=[O:43])C.[Na+]>ClCCCl>[CH3:18][N:15]1[C:14]([CH2:19][N:38]2[CH2:39][CH2:40][CH:35]([CH:33]3[CH2:34][O:31][CH2:32]3)[CH2:36][CH2:37]2)=[N:13][C:12]2[C:16]1=[N:17][C:9]([N:8]1[C:7]3[CH:27]=[CH:28][CH:29]=[CH:30][C:6]=3[N:5]=[C:4]1[CH:3]([OH:43])[CH3:2])=[N:10][C:11]=2[N:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1

参加物

5

反応物 3

HCID 5049666Sodium triacetoxyborohydrideHCID 552642454-(Oxetan-3-yl)piperidineHCID 596052312-[2-(2-Hydroxyethyl)benzoimidazol-1-yl]-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde

生成物 1

HCID 866679201-((9-methyl-6-morpholino-8-((4-(oxetan-3-yl)piperidin-1-yl)methyl)-9H-purin-2-yl)-1H-benzo[d]imidazol-2-yl)ethanol収率 20%

試薬・触媒・溶媒 1

HCID 111,2-Dichloroethane溶媒

実験手順

A solution of 2-[2-(2-hydroxyethyl)benzoimidazol-1-yl]-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (200 mg, 0.49 mmol), 4-oxetan-3-ylpiperidine (83 mg, 0.59 mmol) and molecular sieves (4 Å, powdered, 1 g) in DCE (5 mL) was stirred at ambient temperature for 5 h. Sodium triacetoxyborohydride (156 mg, 0.74 mmol) was added and the mixture stirred for 18 h, then loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was then washed with methanol and the desired product was subsequently eluted using 2 M NH3 in MeOH. The product was collected and concentrated in vacuo. The resultant residue was purified by flash chromatography (Si—PPC, DCM:MeOH; 100:0 to 99:1 to 98:2 to 97:3 to 95:5) to afford 512 as a white solid (51 mg, 20%). LCMS (Method I): RT=2.39 min, M+H+=533. 1H NMR (CDCl3, 400 MHz) δ 8.04 (m, 1 H); 7.75 (m, 1 H); 7.33 (m, 2 H); 4.76 (dd, J=7.8, 6.0 Hz, 2 H); 4.45 (t, J=6.0 Hz, 2 H); 4.35 (m, 4 H); 4.19 (t, J=5.5 Hz, 2 H); 3.94-3.80 (m, 9 H); 3.54 (t, J=5.5 Hz, 2 H); 3.02 (m, 2 H); 2.81-2.72 (m, 1H); 2.29 (m, 2 H); 1.71 (m, 5 H) and 1.28 (m, 1 H)

後処理

  1. washThe cartridge was then washed with methanol
  2. washthe desired product was subsequently eluted
  3. customThe product was collected
  4. concentrationconcentrated in vacuo
  5. customThe resultant residue was purified by flash chromatography (Si—PPC, DCM:MeOH; 100:0 to 99:1 to 98:2 to 97:3 to 95:5)

出典と根拠

ORDレコード
ord-3503afabe0ab468bbdecd2190229bf8f
出典データセット
uspto-grants-2013_03
特許番号
US08394796B2

反応ノート

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