Triethylamine → HCID 59646781, compound

HRID 1365748Notes

Reaction equation

HRID 1365748 reaction equation
[CH2:1]([O:8][C:9]1[C:18](=[O:19])[N:17]2[C:12]([C:13]([CH3:21])([CH3:20])[O:14][CH2:15][CH2:16]2)=[N:11][C:10]=1[C:22](O)=[O:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.Cl.[CH3:27][C:28]1[S:29][C:30]([CH2:33][NH2:34])=[CH:31][N:32]=1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>C(#N)C.C(OCC)(=O)C>[CH2:1]([O:8][C:9]1[C:18](=[O:19])[N:17]2[C:12]([C:13]([CH3:21])([CH3:20])[O:14][CH2:15][CH2:16]2)=[N:11][C:10]=1[C:22]([NH:34][CH2:33][C:30]1[S:29][C:28]([CH3:27])=[N:32][CH:31]=1)=[O:23])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 210698583-(Benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxylic acidHCID 66930264HCID 66930264, compound

Product 1

HCID 59646781HCID 59646781, compoundYield 92.3%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxylic acid (0.200 g, 0.605 mmol) and (2-methylthiazol-5-yl)methanamine dihydrochloride salt (0.135 g, 0.67 mmol) in acetonitrile (15 ml) was treated at 25° C. with triethylamine (0.40 ml, 2.9 mmol) followed by benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphoniumhexafluorophosphate (0.30 g, 0.68 mmol). After 3 hours, the reaction mixture was diluted with ethyl acetate, washed successively with saturated sodium bicarbonate and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Chromatography of the residue on silica gel (elution ethyl acetate) followed by crystallization from ethyl acetate gave 0.246 g (92% yield) of the title amide as white crystals; mp 167° C. 1HNMR 400 MHz (CDCl3) δ (ppm): 1.64 (6H, s, 2×CH3), 2.70 (3H, s, CH3), 4.0-4.08 (4H, m, 2×CH2), 4.68 (2H, d, J=5.8 Hz, NCH2), 5.32 (2H, s, OCH2), 7.34-7.39 (3H, m, aromatics), 7.49 (1H, s, CH), 7.50-7.53 (2H, m, aromatics), 7.72 (1H, broad t, NH). Anal. Calcd for C22H24N4O4S: C, 59.98; H, 5.49; N, 12.71; Found: C, 59.99; H, 5.31; N, 12.61.

Workup

  1. washwashed successively with saturated sodium bicarbonate and brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customChromatography of the residue on silica gel (elution ethyl acetate) followed by crystallization from ethyl acetate

Sources & evidence

ORD record
ord-358a5d0bea924d35bd48b202df481fbf
Source dataset
uspto-grants-2011_02
Patent number
US07893055B2

Reaction notes

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