Hydrochloric Acid → HCID 178511941, compound

HRID 1622165Notes

Reaction equation

HRID 1622165 reaction equation
[C:1]([C:4]1[CH:34]=[CH:33][C:7]2[NH:8][C:9]([C:11]3[CH:12]=[C:13]([CH2:29][C:30](O)=[O:31])[CH:14]=[C:15]([C:18]4[CH:23]=[C:22]([S:24](=[O:27])(=[O:26])[NH2:25])[CH:21]=[CH:20][C:19]=4[OH:28])[C:16]=3[OH:17])=[N:10][C:6]=2[CH:5]=1)(=[NH:3])[NH2:2].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.CC1C(C)=C(C)C=CN=1.[NH2:68][CH2:69][CH2:70][N:71]1[CH2:76][CH2:75][O:74][CH2:73][CH2:72]1.Cl.C(#N)C>CN(C)C=O>[C:1]([C:4]1[CH:34]=[CH:33][C:7]2[NH:8][C:9]([C:11]3[CH:12]=[C:13]([CH2:29][C:30]([NH:68][CH2:69][CH2:70][N:71]4[CH2:76][CH2:75][O:74][CH2:73][CH2:72]4)=[O:31])[CH:14]=[C:15]([C:18]4[CH:23]=[C:22]([S:24](=[O:27])(=[O:26])[NH2:25])[CH:21]=[CH:20][C:19]=4[OH:28])[C:16]=3[OH:17])=[N:10][C:6]=2[CH:5]=1)(=[NH:3])[NH2:2]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 6342AcetonitrileHCID 166912,3,4-TrimethylpyridineHCID 4082852-MorpholinoethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178511944HCID 178511944, compound

Product 1

HCID 178511941HCID 178511941, compoundYield 53.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-acetic acid (96 mg, 0.20 mmol), prepared as in Reference 9, was dissolved in dry N,N-dimethylformamide (20 mL) and the solution was treated with O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (84 mg, 0.22 mmol) and 2,3,4-trimethyl-pyridine (0.106 mL, 0.80 mmol). The mixture was stirred for one hour and then 4-(2-aminoethyl)-morpholine (29 uL, 0.22 mmol) was added. The mixture was stirred until the reaction was complete (½ to 1 hours) and then neutralizated with 1N hydrochloric acid to pH ˜3. The solvents were evaporated at 30° C. to give an oily residue. The crude amide then was prepped at 2:30 (acetonitrile/20 mmol HCl) and the solvents were lyophilized to give 2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-N-(2-morpholin-4-yl-ethyl)-acetamide (63.0 mg, 53%). LCMS: (MH+)=594.3; (MH−)=592.2. NMR (DMSO-d6) δ 2.78 (m, 4H), 3.12 (m, 2H), 3.26 (t, J=3 Hz, 2H), 3.57 (m, 4H), 3.59 (s, 2H), 7.17 (d, J=5 Hz, 1H), 7.23 (br s, 1H), 7.37 (d, J=1.5 Hz, 1H), 7.70 (m, 2H), 7.79 (d of d, J=1.5 Hz, 1H), 7.88 (d, J=5 Hz, 1H), 8.22 (d, J=1 Hz, 1H), 8.24 (s, 1H), 8.59 (t, J=3 Hz, 1H), 9.18, 9.43 (2s, 4H).

Workup

  1. stirringThe mixture was stirred until the reaction
  2. custom(½ to 1 hours)
  3. customThe solvents were evaporated at 30° C.
  4. customto give an oily residue

Sources & evidence

ORD record
ord-da2218a26813445f9daf7ae64eec6bc4
Source dataset
uspto-grants-2014_07
Patent number
US08778625B2

Reaction notes

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