Sodium hydride → (1S,4R)-4-[3-((S)-1-Methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamine

HRID 630699Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 630699
[NH2:1][C@@H:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C@H:5]([OH:12])[CH2:4][CH2:3]1.[H-].[Na+].F[C:16]1[CH:17]=[CH:18][C:19]2[N:20]([C:22]([C@@H:25]3[CH2:29][CH2:28][CH2:27][N:26]3[CH3:30])=[N:23][N:24]=2)[CH:21]=1.[NH4+].[Cl-]>CN(C=O)C>[CH3:30][N:26]1[CH2:27][CH2:28][CH2:29][C@H:25]1[C:22]1[N:20]2[CH:21]=[C:16]([O:12][C@H:5]3[C:6]4[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=4)[C@@H:2]([NH2:1])[CH2:3][CH2:4]3)[CH:17]=[CH:18][C:19]2=[N:24][N:23]=1

Komponenten

6

Edukt 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 86686674(1R,4S)-4-Amino-1,2,3,4-tetrahydronaphthalen-1-olHCID 866870156-Fluoro-3-((S)-1-methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridine

Produkt 1

HCID 117666105(1S,4R)-4-[3-((S)-1-Methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamineAusbeute 36,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

Intermediate A (128 mg, 0.77 mmol) was added portionwise to a suspension of sodium hydride (60% in mineral oil, 92 mg, 2.30 mmol) in dry DMF (3 mL) at RT and stirred for 15 mins. Intermediate 5b (169 mg, 0.77 mmol) was then added in one portion and the mixture heated at 60° C. for 4 h. After cooling, saturated NH4Cl (ca 0.2 mL) was added. The mixture was partitioned between water (10 mL) and ethyl acetate (3×10 mL). The aqueous phase was concentrated in vacuo and the residue purified by SCX-2, eluting with MeOH followed by 2M NH3 in MeOH, to give the title compound as brown coloured foam (103 mg, 36%). LCMS (Method 1): Rt 1.34 min, m/z 364 [MH+].

Aufarbeitung

  1. temperatureAfter cooling
  2. customThe mixture was partitioned between water (10 mL) and ethyl acetate (3×10 mL)
  3. concentrationThe aqueous phase was concentrated in vacuo
  4. customthe residue purified by SCX-2
  5. washeluting with MeOH

Quellen und Nachweise

ORD-Eintrag
ord-c0d36a91457f443c88f75b4e3cd2ede0
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09315503B2

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