Chloroacetyl chloride → 2-chloro-1-[2-(2,3-dihydro-1H-inden-2-ylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl]ethanone

HRID 870562

反応式

HRID 870562 の反応式
[CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH:2]1[NH:10][C:11]1[N:12]=[CH:13][C:14]2[CH2:20][NH:19][CH2:18][CH2:17][C:15]=2[N:16]=1.C(N(CC)CC)C.[Cl:28][CH2:29][C:30](Cl)=[O:31].C(=O)(O)[O-].[Na+]>ClCCl>[Cl:28][CH2:29][C:30]([N:19]1[CH2:18][CH2:17][C:15]2[N:16]=[C:11]([NH:10][CH:2]3[CH2:3][C:4]4[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=4)[CH2:1]3)[N:12]=[CH:13][C:14]=2[CH2:20]1)=[O:31]

参加物

6

反応物 4

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 86726522N-(indan-2-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine

生成物 1

HCID 867265282-chloro-1-[2-(2,3-dihydro-1H-inden-2-ylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl]ethanone収率 69%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To N-indan-2-yl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine (11.0 g, 41.3 mmol) and triethylamine (7.48 mL, 53.7 mmol) in dichloromethane (200 mL), add 2-chloroacetyl chloride (3.61 mL, 5.13 g, 45.4 mmol) dropwise over five minutes at 23° C. Stir for 30 minutes and pour the reaction mixture into 1:1 50% saturated aqueous sodium bicarbonate: dichloromethane (75 mL). Separate the organic layer from the aqueous layer and further extract the aqueous layer with dichloromethane (2×25 mL). Combine the organic extracts and dry over anhydrous sodium sulfate, filter, and concentrate. Dissolve the residue in chloroform (10 mL) and purify via silica gel column chromatography (gradient elution: 25% ethyl acetate in hexanes to 100% ethyl acetate) to give the title compound (9.75 g, 69%). 1H NMR (CDCl3, *=minor amide rotamer) δ 2.77* (t, 2H), 2.84 (dd, 2H), 2.87 (t, 2H), 3.35 (dd, 2H), 3.76 (t, 2H), 3.85* (t, 2H), 4.12 (s, 2H), 4.52* (s, 2H), 4.57 (s, 2H), 4.72-4.82 (m, 1H), 5.48-5.64 (m, 1H), 7.12-7.21 (m, 4H), 8.03-8.10 (m, 1H).

後処理

  1. customSeparate the organic layer from the aqueous layer
  2. extractionfurther extract the aqueous layer with dichloromethane (2×25 mL)
  3. dry with materialCombine the organic extracts and dry over anhydrous sodium sulfate
  4. filtrationfilter
  5. concentrationconcentrate
  6. dissolutionDissolve the residue in chloroform (10 mL)
  7. custompurify via silica gel column chromatography (gradient elution: 25% ethyl acetate in hexanes to 100% ethyl acetate)

出典と根拠

ORDレコード
ord-13388e0e73e74c7fb518858b2c313372
出典データセット
uspto-grants-2015_03
特許番号
US08969555B2

関連ノート

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