Diisopropylethylamine → tert-butyl 4-(5-(4-(butyloxycarbonylaminomethyl)piperidin-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)-2-bromothiazol-5-ylcarbamate

HRID 1185278Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1185278
[CH2:1]1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)C[CH2:2]1.F[P-](F)(F)(F)(F)F.[Br:34][C:35]1[S:36][C:37]([NH:43][C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])=[C:38]([C:40]([OH:42])=O)[N:39]=1.[NH2:51][C:52]1[CH:53]=[N:54][N:55]([CH3:72])[C:56]=1[N:57]1[CH2:62][CH2:61][CH:60]([CH2:63][NH:64][C:65](=[O:71])[O:66][C:67]([CH3:70])(C)C)[CH2:59][CH2:58]1.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH2:67]([O:66][C:65]([NH:64][CH2:63][CH:60]1[CH2:59][CH2:58][N:57]([C:56]2[N:55]([CH3:72])[N:54]=[CH:53][C:52]=2[NH:51][C:40]([C:38]2[N:39]=[C:35]([Br:34])[S:36][C:37]=2[NH:43][C:44](=[O:45])[O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:42])[CH2:62][CH2:61]1)=[O:71])[CH2:70][CH2:1][CH3:2]

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 581821562-Bromo-5-((tert-butoxycarbonyl)amino)thiazole-4-carboxylic acidHCID 58464964tert-butyl (1-(4-amino-1-methyl-1H-pyrazol-5-yl)piperidin-4-yl)methylcarbamate

Produkt 1

HCID 58464898tert-butyl 4-(5-(4-(butyloxycarbonylaminomethyl)piperidin-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)-2-bromothiazol-5-ylcarbamateAusbeute 96,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel3×

Versuchsvorschrift

A solution of PyBOP (2.84 g, 5.46 mmol) and 2-bromo-5-(tert-butoxycarbonylamino)thiazole-4-carboxylic acid (1.39 g, 4.29 mmol) in DCM (10 mL) was stirred at room temperature for 30 min. A solution of tert-butyl (1-(4-amino-1-methyl-1H-pyrazol-5-yl)piperidin-4-yl)methylcarbamate (1.2 g, 3.90 mmol) and DIPEA (1.1 mL, 6.24 mmol) in DCM (20 mL) was added and the mixture stirred at room temperature for 16 hr. The mixture was diluted with DCM and washed with water. The organic layer was separated, passed through a phase separation cartridge and concentrated under reduced pressure. The residue was purified via silica gel column chromatography (0-100% EtOAc/isohexane) to yield tert-butyl 4-(5-(4-(butyloxycarbonylaminomethyl)piperidin-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)-2-bromothiazol-5-ylcarbamate as a pink solid (2.32 g, 96%). 1H NMR (400 MHz, d6-DMSO) δ 10.62 (s, 1H), 9.64 (s, 1H), 7.23 (s, 1H), 6.86 (t, J=5.8 Hz, 1H), 3.62 (s, 3H), 3.07 (d, J=11.4 Hz, 2H), 2.95 (t, J=11.5 Hz, 2H), 2.87 (t, J=6.3 Hz, 2H), 1.67 (d, J=12.3 Hz, 2H), 1.52 (s, 9H), 1.45 (s, 1H), 1.40 (s, 9H), 1.27-1.16 (m, 2H).

Aufarbeitung

  1. washwashed with water
  2. customThe organic layer was separated
  3. custompassed through a phase separation cartridge
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified via silica gel column chromatography (0-100% EtOAc/isohexane)

Quellen und Nachweise

ORD-Eintrag
ord-ee7191ccaa9847e9af958ce470ed3844
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08669361B2

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