Triethylamine → HCID 54692287, compound

HRID 1162833Notes

Reaction equation

HRID 1162833 reaction equation
OC(C(F)(F)F)=O.[F:8][C:9]1[CH:36]=[CH:35][C:12]([CH2:13][N:14]2[CH2:33][CH2:32][N:17]3[C:18](=[O:31])[N:19]([CH2:24][CH:25]4[CH2:30][O:29][CH2:28][CH2:27][NH:26]4)[C:20](=[O:23])[C:21]([OH:22])=[C:16]3[C:15]2=[O:34])=[CH:11][CH:10]=1.Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.[CH3:67][N:68]([C:70](=[O:74])[C:71](O)=[O:72])[CH3:69]>CN(C=O)C>[F:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:13][N:14]2[CH2:33][CH2:32][N:17]3[C:18](=[O:31])[N:19]([CH2:24][CH:25]4[CH2:30][O:29][CH2:28][CH2:27][N:26]4[C:71](=[O:72])[C:70]([N:68]([CH3:69])[CH3:67])=[O:74])[C:20](=[O:23])[C:21]([OH:22])=[C:16]3[C:15]2=[O:34])=[CH:35][CH:36]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2760995N,N-Dimethyloxamic acidHCID 27960291-Hydroxybenzotriazole hydrateHCID 131728411HCID 131728411, compound

Product 1

HCID 54692287HCID 54692287, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(4-Fluorobenzyl)-9-hydroxy-7-(morpholin-3-ylmethyl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,6,8(7H)-trione mono TFA salt (50 mg, 0.096 mmol, from Example 17) in DMF (1 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (28 mg, 0.145 mmol), 1-hydroxybenzotriazole hydrate (22 mg, 0.145 mmol), triethylamine (30 μL, 0.212 mmol), and (dimethylamino)(oxo)acetic acid (22 mg, 0.12 mmol). The reaction was stirred overnight at room temperature and equal amount of the reagents were added to the flask in the morning. After two hours the reaction was purified by prep HPLC on a C18 stationary phase with a water/acetonitrile/TFA gradient. The title compound as obtained as a white solid after lyophilization from dioxane. 1H NMR (400 MHz, d6 DMSO) Mixture of rotamers, approximately 1:1. δ 11.8 (2bs, 1H), 7.40 (m, 2H), 7.21 (m, 2H), 4.61-4.77 (m, 4H), 4.05 (m, 0.5H), 3.78-3.99 (m, 5H), 3.67 (m, 0.5H), 3.55-3.61 (m, 3H), 3.31-3.43 (m, 1.5H), 3.08 (m, 0.5H), 2.84, 2.81 (2s, 3H), and 2.76, 2.75 (2s, 3H). HRMS (FT-ICR) C23H26FN5O7+H=504.1873; calculated 504.1889.

Workup

  1. additionequal amount of the reagents were added to the flask in the morning
  2. customAfter two hours the reaction was purified by prep HPLC on a C18 stationary phase with a water/acetonitrile/TFA gradient

Sources & evidence

ORD record
ord-0602216c64c248ab804ee39d3a77ed65
Source dataset
uspto-grants-2010_10
Patent number
US07820680B2

Reaction notes

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