Glycolic Acid → 6-bromo-4-(((3aS,4R,5R,6aS)-2-(2-hydroxyacetyl)-4-methyloctahydrocyclopenta[c]pyrrol-5-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide

HRID 877737Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 877737
C(N(CC)C(C)C)(C)C.OC(C(F)(F)F)=O.[Br:17][C:18]1[CH:19]=[C:20]2[C:25]([NH:26][C@@H:27]3[CH2:34][C@@H:30]4[CH2:31][NH:32][CH2:33][C@@H:29]4[C@H:28]3[CH3:35])=[C:24]([C:36]([NH2:38])=[O:37])[CH:23]=[N:22][N:21]2[CH:39]=1.[OH:40][CH2:41][C:42](O)=[O:43]>CN(C)C=O.C(=O)(O)[O-].[Na+].C(OCC)(=O)C>[Br:17][C:18]1[CH:19]=[C:20]2[C:25]([NH:26][C@@H:27]3[CH2:34][C@@H:30]4[CH2:31][N:32]([C:41](=[O:40])[CH2:42][OH:43])[CH2:33][C@@H:29]4[C@H:28]3[CH3:35])=[C:24]([C:36]([NH2:38])=[O:37])[CH:23]=[N:22][N:21]2[CH:39]=1

Komponenten

7

Edukt 3

HCID 757Glycolic AcidHCID 81531DiisopropylethylamineHCID 867078986-bromo-4-(((3aS,4R,5R,6aS)-4-methyloctahydrocyclopenta[c]pyrrol-5-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide TFA salt

Produkt 1

HCID 682908906-bromo-4-(((3aS,4R,5R,6aS)-2-(2-hydroxyacetyl)-4-methyloctahydrocyclopenta[c]pyrrol-5-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamideAusbeute 94,7 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 516892Sodium BicarbonateLösungsmittel

Versuchsvorschrift

N,N-diisopropylethylamine (0.532 mL, 3.05 mmol) was added to a solution of 6-bromo-4-(((3 aS,4R,5R,6aS)-4-methyloctahydrocyclopenta[c]pyrrol-5-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide TFA salt from Step 2 of Example 59 (250 mg, 0.508 mmol), 2-hydroxyacetic acid (77 mg, 1.016 mmol) and (benzotriazol-1-yloxy)tris(dimethylamine)phosphonium hexafluorophosphate (449 mg, 1.016 mmol) in N,N-dimethylformamide (5 mL). After 1 h at room temperature, the mixture was diluted with saturated sodium bicarbonate (5 mL) and ethyl acetate (100 mL), washed with water, brine, dried (MgSO4) and concentrated to give the expected product (210 mg). This material was used in the next reaction without purification. 1H NMR (400 MHz, methanol-d4) δ ppm 8.13 (1 H, s), 7.63 (1 H, s), 7.03 (1 H, d, J=1.32 Hz), 4.83-4.96 (2 H, m), 4.06-4.36 (2 H, m), 3.43-3.75 (3 H, m), 3.04-3.10 (1 H, m), 2.80-2.85 (1 H, m), 2.41-2.58 (1 H, m), 1.60-1.94 (1 H, m), 1.39-1.56 (1 H, m), 1.08-1.20 (3 H, m), MS (ES+) m/z: 436.1, 438.2 (M+H).

Aufarbeitung

  1. washwashed with water, brine
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-8547f0d29d894f77bc79b027b0117222
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08987268B2

Notizen zur Reaktion

Wird geladen…