Sodium hydride → HCID 24966426、化合物

HRID 1260443

反応式

HRID 1260443 の反応式
[H-].[Na+].[F:3][C:4]1[CH:9]=[C:8]([I:10])[CH:7]=[CH:6][C:5]=1[NH:11][C:12]1[C:21]2[C:20](=[O:22])[NH:19][CH:18]=[N:17][C:16]=2[N:15]([CH3:23])[C:14](=[O:24])[C:13]=1[CH3:25].Cl[CH2:27][C@H:28]1[CH2:32][O:31]C(C)(C)[O:29]1>CN(C=O)C>[OH:29][C@H:28]([CH2:32][OH:31])[CH2:27][N:19]1[C:20](=[O:22])[C:21]2[C:12]([NH:11][C:5]3[CH:6]=[CH:7][C:8]([I:10])=[CH:9][C:4]=3[F:3])=[C:13]([CH3:25])[C:14](=[O:24])[N:15]([CH3:23])[C:16]=2[N:17]=[CH:18]1

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 2734443(R)-(+)-4-(Chloromethyl)-2,2-dimethyl-1,3-dioxolaneHCID 1359290085-(2-Fluoro-4-iodophenylamino)-6,8-dimethylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione

生成物 1

HCID 24966426HCID 24966426、化合物収率 25.1%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

Sodium hydride (67 mg, 3.5 mmol, 5 eq) was stirred in anhydrous DMF (500 μL) for 10 minutes. 5-(2-fluoro-4-iodophenylamino)-6,8-dimethylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione (300 mg, 0.70 mmol, 1 eq, Example 12) in anhydrous DMF (300 μL) was added and the mixture stirred for 10 minutes. (R)-4-(Chloromethyl)-2,2-dimethyl-1,3-dioxolane (180 μL, 1.32 mmol, 5 eq) was added and the mixture subjected to microwave irradiation at 135° C. for 1 hour. The solvent was removed in vacuo. The residue was taken up in H2O (1 mL) and THF (1 mL). 1N HCl (1 mL) was added and the solution stirred at RT for 1 hour. After evaporation in vacuo the residue was purified by HPLC to give 88 mg (25%) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.64 (s, 3H) 2.11 (s, 3H) 3.18 (d, J=5.31 Hz, 1H) 3.32-3.42 (m, 1H) 3.63-3.70 (m, 1H) 3.70-3.82 (m, 1H) 4.24-4.38 (m, 1H) 4.78 (t, J=5.56 Hz, 1H) 5.09 (d, J=5.56 Hz, 1H) 6.62 (t, J=8.72 Hz, 1H) 7.45 (dd, J=7.71, 2.15 Hz, 1H) 7.66 (dd, J=10.61, 2.02 Hz, 1H) 8.48 (s, 1H) 10.16 (s, 1H) [M+H] calc'd for C18H18FIN4O4, 501. found, 501.

後処理

  1. customirradiation at 135° C. for 1 hour
  2. customThe solvent was removed in vacuo
  3. addition1N HCl (1 mL) was added
  4. stirringthe solution stirred at RT for 1 hour
  5. customAfter evaporation in vacuo the residue
  6. customwas purified by HPLC

出典と根拠

ORDレコード
ord-4398aa6863fd436493d3951d1f54e7c5
出典データセット
uspto-grants-2013_06
特許番号
US08470837B2

関連ノート

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