Triethylamine → N-[2-amino-4-(6-iodo-1H-indazol-1-yl)pyrimidin-5-yl]-3-methyloxetane-3-carboxamide

HRID 1398495Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1398495
[CH3:1][C:2]1([C:6]([OH:8])=O)[CH2:5][O:4][CH2:3]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[I:33][C:34]1[CH:42]=[C:41]2[C:37]([CH:38]=[N:39][N:40]2[C:43]2[C:48]([NH2:49])=[CH:47][N:46]=[C:45]([NH2:50])[N:44]=2)=[CH:36][CH:35]=1.C(N(CC)CC)C>CN(C=O)C.CCOC(C)=O>[NH2:50][C:45]1[N:44]=[C:43]([N:40]2[C:41]3[C:37](=[CH:36][CH:35]=[C:34]([I:33])[CH:42]=3)[CH:38]=[N:39]2)[C:48]([NH:49][C:6]([C:2]2([CH3:1])[CH2:5][O:4][CH2:3]2)=[O:8])=[CH:47][N:46]=1

Komponenten

7

Edukt 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 140289973-Methyl-3-oxetanecarboxylic AcidHCID 681817304-(6-iodo-1H-indazol-1-yl)pyrimidine-2,5-diamine

Produkt 1

HCID 68181899N-[2-amino-4-(6-iodo-1H-indazol-1-yl)pyrimidin-5-yl]-3-methyloxetane-3-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a mixture of 3-methyloxetane-3-carboxylic acid (8.7 mg, 0.075 mmol) and HATU (28.5 mg, 0.075 mmol) was added a solution of crude 4-(6-iodo-1H-indazol-1-yl)pyrimidine-2,5-diamine (11% purity, 120 mg, 0.037 mmol) in DMF (0.5 mL) followed by triethylamine (0.016 mL, 0.112 mmol). The mixture was stirred at RT for 10 min, then diluted with EtOAc (10 mL) and washed with water (2×3 mL). The combined organic layer was dried over Na2SO4, filtered and concentrated in vacuo to give the crude compound. Purification by flash chromatography (Isolute column, 100% DCM to 3% MeOH in DCM) gave the title compound; m/z=+451.30 (M+H)+, (purity=76%). This intermediate was used in the next step without further purification.

Aufarbeitung

  1. washwashed with water (2×3 mL)
  2. dry with materialThe combined organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto give the crude compound
  6. customPurification by flash chromatography (Isolute column, 100% DCM to 3% MeOH in DCM)

Quellen und Nachweise

ORD-Eintrag
ord-de44690b126c4065b7772c219a60f29d
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08901313B2

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