N,N-Dimethyloxamic acid → N'-(2-(5-(4-Fluorobenzyl)-1,3-thiazol-2-yl)-3-hydroxy-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)-N,N-dimethylethanediamide

HRID 80704Notes

Reaction equation

HRID 80704 reaction equation
[NH2:1][C:2]12[CH2:10][CH2:9][CH:6]([CH2:7][CH2:8]1)[CH2:5][N:4]1[C:11](=[O:36])[C:12]([O:28]CC3C=CC=CC=3)=[C:13]([C:15]3[S:16][C:17]([CH2:20][C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=4)=[CH:18][N:19]=3)[N:14]=[C:3]21.[CH3:37][N:38]([CH3:44])[C:39](=[O:43])[C:40](O)=[O:41].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CN(C1C=CN=CC=1)C>[F:27][C:24]1[CH:23]=[CH:22][C:21]([CH2:20][C:17]2[S:16][C:15]([C:13]3[N:14]=[C:3]4[C:2]5([NH:1][C:40](=[O:41])[C:39]([N:38]([CH3:44])[CH3:37])=[O:43])[CH2:8][CH2:7][CH:6]([CH2:9][CH2:10]5)[CH2:5][N:4]4[C:11](=[O:36])[C:12]=3[OH:28])=[N:19][CH:18]=2)=[CH:26][CH:25]=1

Participants

6

Reactant 3

HCID 2760995N,N-Dimethyloxamic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 6796026810-amino-3-(benzyloxy)-2-(5-(4-fluorobenzyl)-1,3-thiazol-2-yl)-7,8,9,10-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-4(6H)-one

Product 1

HCID 136159586N'-(2-(5-(4-Fluorobenzyl)-1,3-thiazol-2-yl)-3-hydroxy-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)-N,N-dimethylethanediamideYield 15.32%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 10-amino-3-(benzyloxy)-2-(5-(4-fluorobenzyl)-1,3-thiazol-2-yl)-7,8,9,10-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-4(6H)-one, Example 5 (35 mg, 0.085 mmol) in DMF (2 mL) was added 2-(dimethylamino)-2-oxoacetic acid (19.87 mg, 0.170 mmol), N,N-diisoproplylethylamine (0.119 mL, 0.679 mmol), HATU (64.5 mg, 0.170 mmol) and DMAP (5.18 mg, 0.042 mmol) and the resulting mixture stirred at room temperature for 16 h. The mixture was purified by preparative HPLC to afford the title compound (7 mg, 0.013 mmol, 15.32% yield) as a light green solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.17 (1H, br. s.), 9.04 (1H, br. s.), 7.87 (1H, br. s.), 7.36 (2H, dd, J=8.16, 5.65 Hz), 7.19 (2H, t, J=8.78 Hz), 4.29 (2H, s), 4.06 (2H, d, J=3.51 Hz), 3.04 (3H, s), 2.87 (3H, s), 2.33-2.45 (3H, m), 2.03-2.14 (2H, m), 1.79-1.90 (2H, m), 1.60-1.71 (2H, m). LCMS (M+H)=512.01.

Workup

  1. customThe mixture was purified by preparative HPLC

Sources & evidence

ORD record
ord-fdb635e6cc3e4b64a429941514f9e560
Source dataset
uspto-grants-2014_09
Patent number
US08846659B2

Reaction notes

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