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

Reaktionsgleichung

Reaktionsgleichung von HRID 870562
[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]

Komponenten

6

Edukt 4

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

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).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-13388e0e73e74c7fb518858b2c313372
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08969555B2

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