Diisopropylethylamine → N,N-Diethyl-N'-(2-((4-fluorobenzyl)carbamoyl)-3-hydroxy-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)ethanediamide

HRID 1093129Notes

Reaction equation

HRID 1093129 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:27])[C:12]([OH:26])=[C:13]([C:15]([NH:17][CH2:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)=[O:16])[N:14]=[C:3]21.[CH2:28]([N:30]([CH2:36][CH3:37])[C:31](=[O:35])[C:32](O)=[O:33])[CH3:29].C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CN(C=O)C.CN(C)C1C=CN=CC=1>[CH2:28]([N:30]([CH2:36][CH3:37])[C:31](=[O:35])[C:32]([NH:1][C:2]12[CH2:8][CH2:7][CH:6]([CH2:9][CH2:10]1)[CH2:5][N:4]1[C:11](=[O:27])[C:12]([OH:26])=[C:13]([C:15](=[O:16])[NH:17][CH2:18][C:19]3[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=3)[N:14]=[C:3]21)=[O:33])[CH3:29]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 4180752(Diethylamino)(oxo)acetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 5790475010-Amino-N-(4-fluorobenzyl)-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxamide

Product 1

HCID 57904919N,N-Diethyl-N'-(2-((4-fluorobenzyl)carbamoyl)-3-hydroxy-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)ethanediamideYield 49.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 10-amino-N-(4-fluorobenzyl)-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxamide (50 mg, 0.122 mmol) in DMF (3 mL) was added 2-(diethylamino)-2-oxoacetic acid (35.5 mg, 0.245 mmol), diisopropyl-ethylamine (0.128 mL, 0.734 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) (93 mg, 0.245 mmol) and 4-(dimethylamino)pyridine (DMAP) (2.99 mg, 0.024 mmol) and the resulting mixture stirred at room temperature for 3 h. After work-up, the crude was then purified by prep HPLC to afford the title compound as a white solid (30 mg, 49% yield). 1H NMR (500 MHz, CDCl3) δ: 12.0 (1 H, brs), 8.7 (1 H, brs), 8.2 (1 H, s), 7.4 (2 H, dd, J=8.09, 5.65 Hz), 7.0 (2 H, t, J=8.55 Hz), 4.6 (2 H, d, J=6.41 Hz), 4.2 (2 H, d, J=3.66 Hz), 3.6 (2 H, q, J=6.82 Hz), 3.3 (2 H, q, J=7.02 Hz), 2.5-2.6 (3 H, m), 2.0-2.1 (2 H, m), 1.9-2.0 (2 H, m), 1.7-1.7 (2 H, m), 1.2 (3 H, t, J=7.02 Hz), 1.1 (3 H, t, J=7.02 Hz). LCMS (M+H)=500.45. HPLC purity: >95%.

Workup

  1. customAfter work-up, the crude was then purified by prep HPLC

Sources & evidence

ORD record
ord-82365986a80f49c48aa12d661c4088e6
Source dataset
uspto-grants-2012_03
Patent number
US08129398B2

Reaction notes

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