Water → HCID 66610679、化合物

HRID 1621454ノート

反応式

HRID 1621454 の反応式
[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[CH:7]=[C:8]([C:13]2[N:21]=[C:20]([CH3:22])[N:19]=[C:18]3[C:14]=2[N:15]=[CH:16][N:17]3[CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][O:24]2)[C:9](F)=[N:10][CH:11]=1.[NH2:29][C:30]1[CH:31]=[CH:32][C:33]([O:36][CH3:37])=[N:34][CH:35]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.O>O1CCCC1>[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[CH:7]=[C:8]([C:13]2[N:21]=[C:20]([CH3:22])[N:19]=[C:18]3[C:14]=2[N:15]=[CH:16][N:17]3[CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][O:24]2)[C:9]([NH:29][C:30]2[CH:35]=[N:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=2)=[N:10][CH:11]=1

参加物

6

反応物 4

HCID 962WaterHCID 811216-Methoxy-3-pyridinylamineHCID 2733832Lithium HexamethyldisilazideHCID 666114866-(5-(1,3-dioxolan-2-yl)-2-fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

生成物 1

HCID 66610679HCID 66610679、化合物収率 77.8%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

6-(5-(1,3-Dioxolan-2-yl)-2-fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (4.557 g, 11.82 mmol) and 5-amino-2-methoxypyridine (1.507 g, 12.14 mmol) were dissolved in tetrahydrofuran (80 mL) and cooled in an ice water bath. Then, LiHMDS (Aldrich 1.0 M in THF, 36.0 mL, 36.0 mmol) was added via syringe over about 10 minutes. The reaction was stirred under nitrogen at 0° C. for 40 minutes, and then the reaction was treated with water (100 mL) and warmed to room temperature. The layers were separated, and the aqueous phase was extracted with DCM. The aqueous phase was diluted with brine and extraction with DCM was continued. The combined organic extracts were combined, dried over sodium sulfate, filtered, concentrated, and purified on a silica gel filter (600 mL fritted filter, about 3 inches of silica gel, 80:1 DCM/2N ammonia in MeOH to 50:1 DCM/2N ammonia in MeOH) to give 5-(1,3-dioxolan-2-yl)-N-(6-methoxypyridin-3-yl)-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-amine (4.500 grams, 71% purity, 52% yield over two steps). MS MS (ESI pos. ion) m/z 446. Calculated exact mass for C23H23N7O3: 445 (M+—C2H4O). 1H NMR (CDCl3, 400 MHz) δ 12.69 (s, 1H), 9.91 (s, 1H), 8.44 (d, J=2.74 Hz, 1H), 8.41 (d, J=2.15 Hz, 1H), 8.29 (s, 1H), 8.23 (dd, J=8.80 Hz, 2.74 Hz, 1H), 6.79 (d, J=8.80 Hz, 1H), 5.94 (s, 1H), 5.87 (dd, J=10.56 Hz, 2.15 Hz, 1H), 4.24-4.17 (m, 3H), 4.12-4.05 (m, 2H), 3.96 (s, 3H), 3.88-3.79 (m, 1H), 2.91 (s, 3H), 2.19-2.00 (m, 3H), 1.93-1.77 (m, 3H).

後処理

  1. temperaturecooled in an ice water bath
  2. temperaturewarmed to room temperature
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted with DCM
  5. additionThe aqueous phase was diluted with brine and extraction with DCM
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified on a silica gel
  10. filtrationfilter (600 mL fritted filter, about 3 inches of silica gel, 80:1 DCM/2N ammonia in MeOH to 50:1 DCM/2N ammonia in MeOH)

出典と根拠

ORDレコード
ord-51bdc4887dbd4a53ad048904f0bf8ad9
出典データセット
uspto-grants-2014_07
特許番号
US08772480B2

反応ノート

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