N,N-Dimethylglycine → Tert-butyl 4-((2-(5-cyanopyrazin-2-ylamino)-5-(2-(dimethylamino)acetamido)pyridin-4-yloxy)methyl)piperidine-1-carboxylate

HRID 384653Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 384653
CN(C)CCCN=C=NCC.[NH2:12][C:13]1[C:14]([O:28][CH2:29][CH:30]2[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]2)=[CH:15][C:16]([NH:19][C:20]2[CH:25]=[N:24][C:23]([C:26]#[N:27])=[CH:22][N:21]=2)=[N:17][CH:18]=1.[CH3:43][N:44]([CH3:49])[CH2:45][C:46](O)=[O:47].O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C>CN(C=O)C>[C:26]([C:23]1[N:24]=[CH:25][C:20]([NH:19][C:16]2[CH:15]=[C:14]([O:28][CH2:29][CH:30]3[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]3)[C:13]([NH:12][C:46](=[O:47])[CH2:45][N:44]([CH3:49])[CH3:43])=[CH:18][N:17]=2)=[N:21][CH:22]=1)#[N:27]

Komponenten

7

Edukt 5

HCID 673N,N-DimethylglycineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 59613369tert-Butyl 4-((5-amino-2-(5-cyanopyrazin-2-ylamino)pyridin-4-yloxy)methyl)piperidine-1-carboxylate

Produkt 1

HCID 59613336Tert-butyl 4-((2-(5-cyanopyrazin-2-ylamino)-5-(2-(dimethylamino)acetamido)pyridin-4-yloxy)methyl)piperidine-1-carboxylateAusbeute 14,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

1-[3-(Dimethylamino)propyl]-3-ethylcarbodiimide (95 mg, 0.49 mmol) was added to a solution of tert-butyl 4-((5-amino-2-(5-cyanopyrazin-2-ylamino)pyridin-4-yloxy)methyl)piperidine-1-carboxylate (140 mg, 0.33 mmol), N,N-dimethylglycine (51 mg, 0.49 mmol), 1-hydroxybenzotriazole hydrate (76 mg, 0.49 mmol) and N-ethyldiisopropylamine (86 μL, 0.49 mmol) in DMF (4 mL). The mixture was stirred overnight at room temperature then partitioned between ethyl acetate and water. The organic phase was washed sequentially with water, dilute sodium bicarbonate solution and brine, then dried (Na2SO4) and concentrated. Preparative HPLC gave tert-butyl 4-((2-(5-cyanopyrazin-2-ylamino)-5-(2-(dimethylamino)acetamido)pyridin-4-yloxy)methyl)piperidine-1-carboxylate (24 mg, 14%) as an off-white powder.

Aufarbeitung

  1. customthen partitioned between ethyl acetate and water
  2. washThe organic phase was washed sequentially with water, dilute sodium bicarbonate solution and brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-14e29664bf37459698855c297366e845
Quelldatensatz
uspto-grants-2013_02
Patentnummer
US08367658B2

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