Diisopropylethylamine → N-(4-Fluorobenzyl)-3-hydroxy-10-(methyl(oxo(1-pyrrolidinyl)acetyl)amino)-4-oxo-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxamide

HRID 1093138Notes

Reaction equation

HRID 1093138 reaction equation
[F:1][C:2]1[CH:28]=[CH:27][C:5]([CH2:6][NH:7][C:8]([C:10]2[N:11]=[C:12]3[C:18]4([NH:21][CH3:22])[CH2:19][CH2:20][CH:15]([CH2:16][CH2:17]4)[CH2:14][N:13]3[C:23](=[O:26])[C:24]=2[OH:25])=[O:9])=[CH:4][CH:3]=1.[O:29]=[C:30]([N:34]1[CH2:38][CH2:37][CH2:36][CH2:35]1)[C:31]([OH:33])=O.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)C1C=CN=CC=1.CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][NH:7][C:8]([C:10]2[N:11]=[C:12]3[C:18]4([N:21]([CH3:22])[C:31](=[O:33])[C:30](=[O:29])[N:34]5[CH2:38][CH2:37][CH2:36][CH2:35]5)[CH2:19][CH2:20][CH:15]([CH2:16][CH2:17]4)[CH2:14][N:13]3[C:23](=[O:26])[C:24]=2[OH:25])=[O:9])=[CH:27][CH:28]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 3150858Oxo(pyrrolidin-1-yl)acetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57904894N-(4-Fluorobenzyl)-3-hydroxy-10-(methylamino)-4-oxo-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxamide

Product 1

HCID 57904965N-(4-Fluorobenzyl)-3-hydroxy-10-(methyl(oxo(1-pyrrolidinyl)acetyl)amino)-4-oxo-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxamideYield 40%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of N-(4-fluorobenzyl)-3-hydroxy-10-(methylamino)-4-oxo-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxamide (50 mg, 0.100 mmol) in (DMF (2 mL) was added 2-oxo-2-(pyrrolidin-1-yl)acetic acid (57.2 mg, 0.400 mmol), diisopropyl-ethylamine (0.105 mL, 0.599 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) (152 mg, 0.400 mmol) and 4-(dimethylamino)pyridine (DMAP) (1.221 mg, 9.99 μmol) and the resulting mixture was stirred at room temperature for 3 h. The crude was then purified by preparative HPLC and recrystallized from methanol to afford the title compound as a glassy white crystals (20 mg, 40% yield). 1H NMR (500 MHz, CDCl3) δ: 12.1 (1 H, s), 9.6 (1 H, brs), 7.4-7.4 (2 H, m), 7.0-7.0 (2 H, m), 4.8-4.9 (1 H, m), 4.6-4.7 (1 H, m), 4.4-4.5 (1 H, m), 3.6-3.7 (2 H, m), 3.5 (2 H, t, J=6.71 Hz), 3.3-3.4 (2 H, m), 3.0 (3 H, s), 2.5 (1 H, brs), 1.9-2.1 (9 H, m), 1.7-1.8 (2 H, m). LCMS (M+H)=512.24. HPLC purity: >95%.

Workup

  1. customThe crude was then purified by preparative HPLC
  2. customrecrystallized from methanol

Sources & evidence

ORD record
ord-ad573f584d554d4591cf573a3150feea
Source dataset
uspto-grants-2012_03
Patent number
US08129398B2

Reaction notes

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