2,6-Lutidine → Benzoic acid 2-(2-acetylamino-6-oxo-1,6-dihydro-purin-9-yl)-5-(2-phosphono-vinyl)-tetrahydro-furan-3-yl ester

HRID 2191014ノート

反応式

HRID 2191014 の反応式
[C:1]([NH:4][C:5]1[N:13]=[C:12]2[C:8]([N:9]=[CH:10][N:11]2[CH:14]2[CH:18]([O:19][C:20](=[O:27])[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH2:17][CH:16]([CH:28]=[CH:29][P:30]([O:35]CC)([O:32]CC)=[O:31])[O:15]2)=[C:7]([O:38]C(=O)N(C2C=CC=CC=2)C2C=CC=CC=2)[N:6]=1)(=[O:3])[CH3:2].N1C(C)=CC=CC=1C.Br[Si](C)(C)C>CC#N>[C:1]([NH:4][C:5]1[NH:6][C:7](=[O:38])[C:8]2[N:9]=[CH:10][N:11]([CH:14]3[CH:18]([O:19][C:20](=[O:27])[C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[CH2:17][CH:16]([CH:28]=[CH:29][P:30]([OH:35])([OH:32])=[O:31])[O:15]3)[C:12]=2[N:13]=1)(=[O:3])[CH3:2]

参加物

5

反応物 3

HCID 79372,6-LutidineHCID 76113BromotrimethylsilaneHCID 72247319Benzoic acid 2-(2-acetylamino-6-diphenylcarbamoyloxy-purin-9-yl)-5-[2-(diethoxy-phosphoryl)-vinyl]-tetrahydro-furan-3-yl ester

生成物 1

HCID 136381446Benzoic acid 2-(2-acetylamino-6-oxo-1,6-dihydro-purin-9-yl)-5-(2-phosphono-vinyl)-tetrahydro-furan-3-yl ester収率 48%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

A suspension of compound 9.9 (128 mg, 0.173 mmol) in MeCN (5 mL) was treated with 2,6-lutidine (0.08 mL, 0.7 mmol) and bromotrimethylsilane (0.3 mL, 2.27 mmol) and stirred at room temperature for 2 h. The mixture was evaporated and co-evaporated with MeCN. The residue was dissolved in MeOH—H2O (1:1, 10 mL) and treated with NaOH (1 N, 3 mL). The mixture was stirred at room temperature for 16 h then at 45° C. for 1 h, and concentrated under reduced pressure. The residue was subjected to reverse phase HPLC eluting with 0-25% CH3CN in water to give the desired product 9.10 (32 mg, 48%). 1H NMR (D2O) δ 2.1 (m, 2H), 4.55 (m, 1H), 4.8 (m, 1H), 5.7 (d, 1H, J=1.5), 5.9 (m, 1H), 6.1(m, 1H), 7.7 (s, 1H). 31P NMR (D2O) d 17.17. LRMS (ESI) MH+ C11H14N5O6P requires 344.2. Found 344.0.

後処理

  1. customThe mixture was evaporated
  2. dissolutionThe residue was dissolved in MeOH—H2O (1:1, 10 mL)
  3. additiontreated with NaOH (1 N, 3 mL)
  4. stirringThe mixture was stirred at room temperature for 16 h
  5. waitat 45° C. for 1 h
  6. concentrationconcentrated under reduced pressure
  7. washHPLC eluting with 0-25% CH3CN in water

出典と根拠

ORDレコード
ord-15692087f68442d8b2ded78153491d02
出典データセット
uspto-grants-2012_12
特許番号
US08324179B2

反応ノート

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