Hydrochloric Acid → N-[1-butyl-3-(2-fluoro-benzyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl]-2-[4-(pyridin-2-ylsulfamoyl)-phenyl]-acetamide

HRID 858075Notes

Reaction equation

HRID 858075 reaction equation
[NH2:1][C:2]1[C:3](=[O:22])[N:4]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[F:21])[C:5](=[O:13])[N:6]([CH2:9][CH2:10][CH2:11][CH3:12])[C:7]=1N.[N:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[NH:29][S:30]([C:33]1[CH:38]=[CH:37][C:36]([CH2:39][C:40](O)=[O:41])=[CH:35][CH:34]=1)(=[O:32])=[O:31].C(N(CC)C(C)C)(C)C.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.Cl>CN(C)C=O.O>[CH2:9]([N:6]1[CH:7]=[C:2]([NH:1][C:40](=[O:41])[CH2:39][C:36]2[CH:35]=[CH:34][C:33]([S:30](=[O:31])(=[O:32])[NH:29][C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][N:23]=3)=[CH:38][CH:37]=2)[C:3](=[O:22])[N:4]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[F:21])[C:5]1=[O:13])[CH2:10][CH2:11][CH3:12]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 218917565,6-diamino-1-butyl-3-(2-fluorobenzyl)-1H-pyrimidine-2,4-dioneHCID 24267818[4-(Pyridin-2-ylsulfamoyl)-phenyl]-acetic acid

Product 1

HCID 69115285N-[1-butyl-3-(2-fluoro-benzyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl]-2-[4-(pyridin-2-ylsulfamoyl)-phenyl]-acetamideYield 86%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 5,6-diamino-1-butyl-3-(2-fluoro-benzyl)-1H-pyrimidine-2,4-dione (30.6 mg, 0.1 mmol) and [4-(pyridin-2-ylsulfamoyl)-phenyl]-acetic acid (29.2 mg, 0.1 mmol) in dry N,N-dimethylformamide (1 mL) was treated with N,N-diisopropylethylamine (61 mL, 0.35 mmol) and O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (37.9 mg, 0.1 mmol). The mixture was stirred at 25° C. for 16 h. The reaction mixture was diluted with water and acidified to pH=5.0 with a 0.01M aqueous hydrochloric acid solution. The reaction mixture was extracted with ethyl acetate. The combined organic extracts were washed with water and a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated in vacuo to afford N-[1-butyl-3-(2-fluoro-benzyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl]-2-[4-(pyridin-2-ylsulfamoyl)-phenyl]-acetamide (86%); 1H NMR(CDCl3, 300 MHz) δH 8.20–6.65 (m, 13H), 5.21 (broad s, 2H), 5.02 (s, 2H), 3.79 (t, J=7 Hz, 2H), 3.60 (s, 2H), 1.65–1.20 (m, 4H), 0.85 (t, J=7 Hz, 3H); LRMS for C28H29FN6O5S (M+H)+ at m/z=581.

Workup

  1. extractionThe reaction mixture was extracted with ethyl acetate
  2. washThe combined organic extracts were washed with water
  3. dry with materiala saturated aqueous sodium chloride solution, dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0bec9587debc4f6fbd5daa1ee0bd9cb5
Source dataset
uspto-grants-2006_12
Patent number
US07148229B2

Reaction notes

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