Sodium Carbonate → 4-((2R)-2-{[[(2S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-3-(phenyloxy)propyl](phenylmethyl)amino]methyl}-3,4-dihydro-2H-chromen-6-yl)-2-pyridinecarboxamide

HRID 47684

Reaktionsgleichung

Reaktionsgleichung von HRID 47684
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[O:15][C@@H:14]([CH2:19][N:20]([CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH2:21][C@H:22]([O:31][Si:32]([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33])[CH2:23][O:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:13][CH2:12]3)O1.Cl[C:48]1[CH:53]=[CH:52][N:51]=[C:50]([C:54]([NH2:56])=[O:55])[CH:49]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1.C(O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:38][C:35]([Si:32]([CH3:34])([CH3:33])[O:31][C@H:22]([CH2:23][O:24][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)[CH2:21][N:20]([CH2:19][C@H:14]1[CH2:13][CH2:12][C:11]2[C:16](=[CH:17][CH:18]=[C:9]([C:48]3[CH:53]=[CH:52][N:51]=[C:50]([C:54]([NH2:56])=[O:55])[CH:49]=3)[CH:10]=2)[O:15]1)[CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)([CH3:36])[CH3:37]

Komponenten

8

Edukt 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 3035434-Chloropyridine-2-carboxamideHCID 60071933(2S)-N-benzyl-2-{[tert-butyl(dimethyl)silyl]oxy}-3-phenoxy-N-{[(2R)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-chromen-2-yl]methyl}propan-1-amine

Produkt 1

HCID 590608044-((2R)-2-{[[(2S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-3-(phenyloxy)propyl](phenylmethyl)amino]methyl}-3,4-dihydro-2H-chromen-6-yl)-2-pyridinecarboxamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 702EthanolLösungsmittelHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

Argon was bubbled through a mixture of (2S)-N-{[(2R)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-chromen-2-yl]methyl}-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-N-(phenylmethyl)-3-(phenyloxy)-1-propanamine (Example 88, 100 mg, 0.16 mmol) and 4-chloro-2-pyridinecarboxamide in toluene (1 mL), ethanol (1 mL), and 2M aqueous sodium carbonate (1 mL) for 10 minutes. Triphenylphosphine (4 mg, 0.016 mmol, 0.1 eq.) and palladium (II) acetate (1.0 mg, 0.004 mmol, 0.025 eq.) were added, and the mixture was stirred vigorously under argon at 85° C. overnight. The reaction was cooled and filtered through a pad of Celite® with the aid of ethyl acetate. The filtrate was concentrated in vacuo to remove excess solvents, and the resulting oil was purified by flash chromatography on silica gel eluted on a gradient from 75:25 to 25:75 hexanes/ethyl acetate. The title compound was obtained as a pale yellow oil (45 mg, 44%): 1H NMR (300 MHz, acetone-d6) δ8.57 (d, 1 H), 8.31 (d, 1 H), 7.96 (broad s, 1 H), 7.76 (dd, 1 H), 7.56-7.53 (m, 2 H), 7.45-7.41 (m, 2 H), 7.34-7.21 (m, 5 H), 6.91-6.86 (m, 4H), 6.80 (broad s, 1 H), 4.35-4.30 (m, 1 H), 4.26-4.18 (m, 2 H), 3.93-3.77 (m, 3 H), 2.98-2.87 (m, 4 H), 2.15-2.08 (m, 1 H), 1.73-1.59 (m, 1 H), 1,30-1.25 (m, 1 H), 0.88 (s, 9 H), 0.12 (s, 3 H), 0.08 (s, 3 H); MS m/z 638.4 (MH+).

Aufarbeitung

  1. temperatureThe reaction was cooled
  2. filtrationfiltered through a pad of Celite® with the aid of ethyl acetate
  3. concentrationThe filtrate was concentrated in vacuo
  4. customto remove excess solvents
  5. customthe resulting oil was purified by flash chromatography on silica gel
  6. washeluted on a gradient from 75:25 to 25:75 hexanes/ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-18628cf1a5f145ae89ab206458059a7c
Quelldatensatz
uspto-grants-2004_03
Patentnummer
US06699860B2

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