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Triethylamine → n-{4-Fluoro-2-(methylcarbamoyl)benzyl}-3-benzyloxy-9-methyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide

HRID 1788171
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1788171
[CH2:1]([O:8][C:9]1[C:18](=[O:19])[N:17]2[C:12]([CH:13]([CH3:20])[O:14][CH2:15][CH2:16]2)=[N:11][C:10]=1[C:21]([OH:23])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O.[NH2:31][CH2:32][C:33]1[CH:42]=[CH:41][C:40]([F:43])=[CH:39][C:34]=1[C:35]([NH:37][CH3:38])=[O:36].C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1>ClCCl.C(OCC)(=O)C>[F:43][C:40]1[CH:41]=[CH:42][C:33]([CH2:32][NH:31][C:21]([C:10]2[N:11]=[C:12]3[N:17]([C:18](=[O:19])[C:9]=2[O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:16][CH2:15][O:14][CH:13]3[CH3:20])=[O:23])=[C:34]([C:35](=[O:36])[NH:37][CH3:38])[CH:39]=1
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Komponenten

7

Edukt 4

HCID 8471TriethylamineHCID 2724699PyBOPHCID 210698142-(Aminomethyl)-5-fluoro-n-methylbenzamide trifluoroacetate saltHCID 210698603-Benzyloxy-9-methyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxylic acid

Produkt 1

HCID 21070023n-{4-Fluoro-2-(methylcarbamoyl)benzyl}-3-benzyloxy-9-methyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide
Ausbeute 100,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A mixture of intermediate 27, 3-benzyloxy-9-methyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxylic acid (0.172 g, 0.54 mmol) and intermediate 39, 2-(aminomethyl)-5-fluoro-N-methylbenzamide trifluoroacetate salt (0.177 g, 0.60 mmol) in dichloromethane (10 ml) was treated at 22° C. with triethylamine (0.17 ml, 1.22 mmol) followed by benzotriazole-1-yloxy-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBOP) (0.340 g, 0.65 mmol). After 3 h, the reaction mixture was diluted with ethyl acetate, washed with saturated sodium bicarbonate and brine then dried over anhydrous magnesium sulfate. Evaporation of the solvent followed by chromatography of the residue on silica gel (elution gradient ethyl acetate 50-100% in toluene) gave 0.260 g (100% yield) of the title amide as a white solid. 1HNMR 400 MHz (CDCl3) δ (ppm): 1.70 (3H, d, J=6.6 Hz, CH3), 3.01 (3H, d, J=4.7 Hz, NCH3), 3.89 (2H, m, CH2), 4.14 (1H, m, CH), 4.29 (1H, m, CH), 4.53 (2H, d, J=6.7 Hz, NCH2), 4.69 (1H, q, J=6.6 Hz, OCH), 5.35 (2H, s, OCH2), 6.69 (1H, broad q, NH), 7.09 (1H, m, aromatic), 7.16 (1H, m, aromatic), 7.32 (3H, m, aromatics), 7.42 (1H, m, aromatic), 7.47 (2H, m, aromatics), 8.61 (1H, broad t, NH). HRMS (ESI+) calculated for C25H26FN4O5 [M+H+]: 481.1887: found: 481.1884.

Aufarbeitung

  1. washwashed with saturated sodium bicarbonate and brine
  2. dry with materialthen dried over anhydrous magnesium sulfate
  3. customEvaporation of the solvent

Quellen und Nachweise

ORD-Eintrag
ord-bfccd046a655437f87615e946c9cf0a5
Quelldatensatz
uspto-grants-2009_03
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07511037B2

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