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1,2-Dichloroethane → 3-(trans-3-Cyclopropylmethoxytetrahydrofuran-4-ylamino)-6-chloro-1-(3-chloro-7-azaindol-5-ylmethylaminocarbonylmethyl)pyrazinone

HRID 398395
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Reaktionsgleichung

Reaktionsgleichung von HRID 398395
[CH:1]1([CH2:4][O:5][C@H:6]2[C@H:10]([NH:11][C:12]3[C:13](=[O:23])[N:14]([CH2:19][C:20]([OH:22])=O)[C:15]([Cl:18])=[CH:16][N:17]=3)[CH2:9][O:8][CH2:7]2)[CH2:3][CH2:2]1.Cl.Cl.[NH2:26][CH2:27][C:28]1[CH:29]=[C:30]2[C:34](=[N:35][CH:36]=1)[NH:33][CH:32]=[C:31]2[Cl:37].C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.C(Cl)CCl.CO>CN(C=O)C.Cl>[CH:1]1([CH2:4][O:5][C@H:6]2[C@H:10]([NH:11][C:12]3[C:13](=[O:23])[N:14]([CH2:19][C:20]([NH:26][CH2:27][C:28]4[CH:29]=[C:30]5[C:34](=[N:35][CH:36]=4)[NH:33][CH:32]=[C:31]5[Cl:37])=[O:22])[C:15]([Cl:18])=[CH:16][N:17]=3)[CH2:9][O:8][CH2:7]2)[CH2:2][CH2:3]1
KomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

9

Edukt 6

HCID 111,2-DichloroethaneHCID 887MethanolHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 230002415-Aminomethyl-3-chloro-7-azaindole bis-hydrochloride saltHCID 700236133-(trans-3-Cyclopropylmethoxytetrahydrofuran-4-ylamino)-6-chloro-1-carboxymethylpyrazinone

Produkt

1
HCID 700233993-(trans-3-Cyclopropylmethoxytetrahydrofuran-4-ylamino)-6-chloro-1-(3-chloro-7-azaindol-5-ylmethylaminocarbonylmethyl)pyrazinone

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 313Hydrochloric AcidLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a stirred solution of 3-(trans-3-cyclopropylmethoxytetrahydrofuran-4-ylamino)-6-chloro-1-carboxymethylpyrazinone from step 7 above (50 mg, 0.15 mmol) in DMF (1.0 mL) was added 5-aminomethyl-3-chloro-7-azaindole bis-hydrochloride salt (41 mg, 0.16 mmol) and HOBT (24 mg, 0.16 mmol). The solution was brought to pH 7 by the addition of DIEA (approximately 0.1 mL). EDC (70 mg, 0.24 mmol) was added and the solution was stirred at ambient temperature for 18 h. The reaction was concentrated in vacuo and partitioned between water and EtOAc. The organic phase was dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography using 9:1 CH2Cl2:MeOH as eluant. The free base of the title compound was dissolved in MeOH containing 3 equivalents of aqueous HCl and the solution was evaporated in vacuo to give the HCl salt of the title compound as an amorphous solid (45 mg, TLC Rf=0.46, 92:8:0.4 CH2Cl2:MeOH:NH4OH; HPLC RT=8.6 min, method A; M+1 peak at m/z=508, electrospray mass spec).

Aufarbeitung

  1. concentrationThe reaction was concentrated in vacuo
  2. custompartitioned between water and EtOAc
  3. dry with materialThe organic phase was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-9b8a72e5e81c41d9912a51af8d36b2f7
Quelldatensatz
uspto-grants-2003_08
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US06610692B1

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