Diisopropylethylamine → HCID 57904970, compound

HRID 1093135Notes

Reaction equation

HRID 1093135 reaction equation
[F:1][C:2]1[CH:37]=[CH:36][C:5]([CH2:6][NH:7][C:8]([C:10]2[N:11]=[C:12]3[C:18]4([NH:21][C:22](=[O:31])[C:23](=[O:30])[N:24]5[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]5)[CH2:19][CH2:20][CH:15]([CH2:16][CH2:17]4)[CH2:14][N:13]3[C:32](=[O:35])[C:33]=2[OH:34])=[O:9])=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.[CH3:47][N:48]([CH3:53])[S:49](Cl)(=[O:51])=[O:50]>ClCCl>[CH3:47][N:48]([CH3:53])[S:49]([N:27]1[CH2:26][CH2:25][N:24]([C:23](=[O:30])[C:22]([NH:21][C:18]23[CH2:19][CH2:20][CH:15]([CH2:16][CH2:17]2)[CH2:14][N:13]2[C:32](=[O:35])[C:33]([OH:34])=[C:10]([C:8]([NH:7][CH2:6][C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:37][CH:36]=4)=[O:9])[N:11]=[C:12]32)=[O:31])[CH2:29][CH2:28]1)(=[O:51])=[O:50]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 83372Dimethylsulphamoyl chlorideHCID 57904939N-(4-Fluorobenzyl)-3-hydroxy-4-oxo-10-((oxo(1-piperazinyl)acetyl)amino)-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxamide

Product 1

HCID 57904970HCID 57904970, compoundYield 49.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of N-(4-fluorobenzyl)-3-hydroxy-4-oxo-10-((oxo(1-piperazinyl)acetyl)amino)-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxamide (0.025 g, 0.040 mmol) in dichloromethane (1 mL) was added diisopropyl ethylamine (0.028 mL, 0.160 mmol) and the solution was stirred at room temperature for 5 min. Added to this was dimethylsulfamoyl chloride (4.26 μL, 0.040 mmol) and the solution was stirred at room temperature for 16 h. The reaction solution was concentrated and purified by preparative HPLC: Solvent A=10% methanol/90% H2O/0-1% trifluoroacetic acid; Solvent B=90% methanol/10% H2O/0.1% trifluoroacetic acid; Start % B=20; Final % B=100; Gradient time=20 min; Stop time=30 min; Column=XTERRA® 19×50 mm, C18, 5 μm to give the title compound as a white solid (12.2 mg, 45% yield). LCMS (M+H) calcd for C27H35FN7O7S: 620.23; found: 620.74. 1H NMR (500 MHz, CDCl3) δ: 12.00 (1 H, s), 8.45 (1 H, s), 8.39 (1 H, t, J=5.95 Hz), 7.36 (2H, dd, J=8.55, 5.49 Hz), 7.01 (2 H, t, J=8.55 Hz), 4.55 (2 H, d, J=6.10 Hz), 4.16 (2 H, d, J=3.66 Hz), 4.02-4.09 (2 H, m), 3.52-3.61 (2 H, m), 3.26-3.36 (2 H, m), 3.18-3.26 (2 H, m), 2.84 (6 H, s), 2.58 (2 H, ddd, J=14.19, 9.16, 5.65 Hz), 2.50 (1H, brs), 1.86-2.11 (4 H, m), 1.66-1.80 (2 H, m).

Workup

  1. stirringthe solution was stirred at room temperature for 16 h
  2. concentrationThe reaction solution was concentrated
  3. custompurified by preparative HPLC
  4. customGradient time=20 min
  5. customtime=30 min

Sources & evidence

ORD record
ord-9be5db69178a41729e35b01cd674fbe3
Source dataset
uspto-grants-2012_03
Patent number
US08129398B2

Reaction notes

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