Dimethylamine → HCID 66588872, compound

HRID 1093148Notes

Reaction equation

HRID 1093148 reaction equation
Cl.[F:2][C:3]1[CH:41]=[CH:40][C:6]([CH2:7][NH:8][C:9]([C:11]2[N:12]=[C:13]3[C@H:20]([NH:21]C(=O)OCC4C=CC=CC=4)[C@@:19]4([CH3:35])[C:32]([CH3:34])([CH3:33])[C@H:16]([CH2:17][CH2:18]4)[CH2:15][N:14]3[C:36](=[O:39])[C:37]=2[OH:38])=[O:10])=[CH:5][CH:4]=1.C(N(C(C)C)CC)(C)C.[CH3:51][S:52](Cl)(=[O:54])=[O:53].N(C)C>C(Cl)Cl.CO>[F:2][C:3]1[CH:41]=[CH:40][C:6]([CH2:7][NH:8][C:9]([C:11]2[N:12]=[C:13]3[C@H:20]([NH:21][S:52]([CH3:51])(=[O:54])=[O:53])[C@@:19]4([CH3:35])[C:32]([CH3:34])([CH3:33])[C@H:16]([CH2:17][CH2:18]4)[CH2:15][N:14]3[C:36](=[O:39])[C:37]=2[OH:38])=[O:10])=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 674DimethylamineHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 131729490HCID 131729490, compound

Product 1

HCID 66588872HCID 66588872, compoundYield 69.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of benzyl ((7S,10R,11R)-2-((4-fluorobenzyl)carbamoyl)-3-hydroxy-10,12,12-trimethyl-4-oxo-6,7,8,9,10,11-hexahydro-4H-7,10-methanopyrimido[1,2-a]azocin-11-yl)carbamate hydrochloride salt (0.025 g, 0.055 mmol) and diisopropyl-ethylamine (0.175 mL, 1 mmol) in CH2Cl2 (3 mL) was added methanesulfonyl chloride (0.039 mL, 0.5 mmol) at room temperature. After 4 h, 2M Me2NH in methanol (1 mL) was added and stirring continued at room temperature. After 16 h, the reaction mixture was concentrated and purified by preparative-HPLC using methanol/water (0.1% trifluoroacetic acid) to afford the title compound (0.0186 g, 0.038 mmol, 68% yield) as a purple solid after crystallization from methanol/water. 1H NMR (500 MHz, CDCl3) δ: 12.39 (1 H, s), 8.60 (1 H, brs), 7.34 (2 H, dd, J=8.5, 5.2 Hz), 7.01 (2 H, t, J=8.7 Hz), 6.07 (1 H, d, J=9.5 Hz), 5.19 (1 H, dd, J=15.6, 8.5 Hz), 4.79 (1 H, d, J=9.8 Hz), 4.52-4.65 (2 H, m), 3.63 (1 H, d, J=15.6 Hz), 2.76 (3 H, s), 2.10 (1 H, t, J=8.1 Hz), 1.80-1.89 (1 H, m), 1.43-1.51 (1 H, m), 1.30-1.35 (1 H, m), 1.29 (3H, s), 1.04 (3 H, s), 1.01 (3 H, s), 0.96-1.01 (1 H, m). LCMS (M+H) calcd for C23H30FN4O5S: 493.19; found: 493.24. Purity: >98%.

Workup

  1. customcontinued at room temperature
  2. waitAfter 16 h
  3. concentrationthe reaction mixture was concentrated
  4. custompurified

Sources & evidence

ORD record
ord-0f5a8bfb0c5b47bd8925b648958e5aa9
Source dataset
uspto-grants-2012_03
Patent number
US08129398B2

Reaction notes

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