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 1055174

반응식

HRID 1055174 반응식
[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]

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-41adfbf7ff734230b48ffd033ab2f855
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09394317B2

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