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Potassium Carbonate → (2S)-methyl 2-(7-(4-allyl-5-chloro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-5-methyl-2-(2'-(pent-4-en-1-yloxy)-[1,1'-biphenyl]-3-yl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

HRID 1400700
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1400700
[CH2:1]([N:4]1[CH2:9][CH2:8][O:7][C:6]2[CH:10]=[CH:11][C:12]([C:15]3[N:20]4[N:21]=[C:22]([C:24]5[CH:25]=[C:26]([C:30]6[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=6[OH:36])[CH:27]=[CH:28][CH:29]=5)[CH:23]=[C:19]4[N:18]=[C:17]([CH3:37])[C:16]=3[C@H:38]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])[C:39]([O:41][CH3:42])=[O:40])=[C:13]([Cl:14])[C:5]1=2)[CH:2]=[CH2:3].C([O-])([O-])=O.[K+].[K+].Br[CH2:55][CH2:56][CH2:57][CH:58]=[CH2:59]>CC(C)=O>[CH2:1]([N:4]1[CH2:9][CH2:8][O:7][C:6]2[CH:10]=[CH:11][C:12]([C:15]3[N:20]4[N:21]=[C:22]([C:24]5[CH:25]=[C:26]([C:30]6[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=6[O:36][CH2:59][CH2:58][CH2:57][CH:56]=[CH2:55])[CH:27]=[CH:28][CH:29]=5)[CH:23]=[C:19]4[N:18]=[C:17]([CH3:37])[C:16]=3[C@H:38]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])[C:39]([O:41][CH3:42])=[O:40])=[C:13]([Cl:14])[C:5]1=2)[CH:2]=[CH2:3]
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Komponenten

5

Edukt 3

HCID 11430Potassium CarbonateHCID 707041-Pentene, 5-bromo-HCID 86710750(2S)-methyl 2-(7-(4-allyl-5-chloro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-2-(2'-hydroxy-[1,1'-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

Produkt 1

HCID 89971579(2S)-methyl 2-(7-(4-allyl-5-chloro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-5-methyl-2-(2'-(pent-4-en-1-yloxy)-[1,1'-biphenyl]-3-yl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate
Ausbeute 45,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 180AcetoneLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

A solution of (2S)-methyl 2-(7-(4-allyl-5-chloro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-2-(2′-hydroxy-[1,1′-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.058 g, 0.089 mmol) and K2CO3 (0.042 g, 0.304 mmol) in dry acetone (5 mL) was treated with 5-bromopent-1-ene (0.026 g, 0.174 mmol), and the reaction was stirred with heating (70° C. oil bath) for 16 h. The reaction was cooled, then concentrated under reduced pressure. The residue was taken up in CH2Cl2 (5 mL) and washed with 1N HCl (5 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by biotage column chromatography (5%-50% EtOAc in hexanes). Product fractions were pooled and concentrated under reduced pressure. The product, (2S)-methyl 2-(7-(4-allyl-5-chloro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-5-methyl-2-(2′-(pent-4-en-1-yloxy)-[1,1′-biphenyl]-3-yl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.031 g, 0.040 mmol, 45.4% yield) was isolated as a clear film. 1H NMR (400 MHz, CDCl3) δ 8.04-7.99 (m, 1H), 7.85-7.79 (m, 1H), 7.54-7.49 (m, 1H), 7.44-7.38 (m, 1H), 7.36 (dd, J=7.5, 1.8 Hz, 1H), 7.31 (td, J=7.8, 1.6 Hz, 1H), 7.03 (td, J=7.5, 0.9 Hz, 1H), 7.01-6.94 (m, 3H), 6.90 (s, 1H), 6.03 (ddt, J=16.9, 10.5, 6.0 Hz, 1H), 5.74 (ddt, J=17.0, 10.3, 6.7 Hz, 1H), 5.33 (dd, J=17.1, 1.5 Hz, 1H), 5.24 (d, J=10.0 Hz, 1H), 5.05 (s, 1H), 4.96-4.86 (m, 2H), 4.26 (t, J=4.4 Hz, 2H), 3.96 (t, J=6.4 Hz, 2H), 3.78-3.69 (m, 1H), 3.65 (s, 3H), 3.64-3.55 (m, 1H), 3.20 (q, J=4.2 Hz, 2H), 2.84 (s, 3H), 2.11 (q, J=6.9 Hz, 2H), 1.83-1.71 (m, 2H), 1.63 (s, 1H), 1.17 (s, 9H). LCMS (M+H)=721.5.

Aufarbeitung

  1. temperatureThe reaction was cooled
  2. concentrationconcentrated under reduced pressure
  3. washwashed with 1N HCl (5 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by biotage column chromatography (5%-50% EtOAc in hexanes)
  8. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-f58cb05bdf0649959420a2b52399fd23
Quelldatensatz
uspto-grants-2014_12
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08906929B2

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