Hydrochloric Acid → HCID 25177313, compound

HRID 1811725Notes

Reaction equation

HRID 1811725 reaction equation
[OH-].[Li+].CO[C:5]([C@@H:7]1[CH2:27][CH2:26][CH2:25][NH:24][C:23](=[O:28])[C:22]2=[CH:29][C:18](=[C:19]([CH3:31])[CH:20]=[C:21]2[CH3:30])[C:17]2[CH:32]=[C:13]([N:14]=[C:15]([NH2:33])[N:16]=2)[S:12][CH2:11][CH2:10][C:9](=[O:34])[NH:8]1)=[O:6].Cl.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(C)N=1.[NH2:69][CH2:70][CH2:71][OH:72]>CN(C)C=O.CO.O1CCCC1>[OH:72][CH2:71][CH2:70][NH:69][C:5]([C@@H:7]1[CH2:27][CH2:26][CH2:25][NH:24][C:23](=[O:28])[C:22]2=[CH:29][C:18](=[C:19]([CH3:31])[CH:20]=[C:21]2[CH3:30])[C:17]2[CH:32]=[C:13]([N:14]=[C:15]([NH2:33])[N:16]=2)[S:12][CH2:11][CH2:10][C:9](=[O:34])[NH:8]1)=[O:6]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 700EthanolamineHCID 3939Lithium HydroxideHCID 79532,4,6-TrimethylpyridineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59224671HCID 59224671, compound

Product 1

HCID 25177313HCID 25177313, compoundYield 21.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

An aqueous solution of 1N lithium hydroxide (0.263 ml) was added at 0° C. to a methanol/tetrahydrofuran solution (1:10 v/v, 2.5 ml) mixed with (S)-4-amino-19,21-dimethyl-10,17-dioxo-7-thia-3,5,11,16-tetraazatricyclo[16.3.1.12,6]tricosa-1(21),2,4,6(23),18(22),19-hexaene-12-carboxylic acid methyl ester (30 mg) obtained in Step 3 of Example 2-9. After stirring for 10 minutes, the mixture was warmed to room temperature and stirred for 1.5 hours. The pH of the reaction solution was adjusted to about 4 using 1N hydrochloric acid. The solution was extracted four times with ethyl acetate (20 ml). The organic layers were combined together, and dried over anhydrous sodium sulfate. After the inorganic salt was removed by filtration, the filtrate was concentrated under reduced pressure to give crude product (39 mg). An aliquot (20 mg) of the crude product was dissolved in N,N-dimethylformamide (1.0 ml), and then 2-3H-1,2,3-triazolo[4,5-b]pyridin-3-ol (7 mg, 0.053 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (20 mg, 0.052 mmol),2,4,6-trimethylpyridine (14 μl), and 2-aminoethanol (3 μl, 0.053 mol) were added thereto at 0° C. After stirring at 0° C. for 30 minutes, the mixture was warmed to room temperature and stirred for 30 minutes. The reaction solution was concentrated under reduced pressure. The resulting crude product was purified by high performance liquid chromatography (developing solvent: A, acetonitrile containing 0.05% trifluoroacetic acid; B, 0.05% aqueous trifluoroacetic acid solution; gradient condition: B, 1% (0 min)→1% (1 min)→30% (7 min)→95% (8 min)→95% (9 min)→1% (10 min); flow rate, 35 ml/min; column, Waters, SunFire PrepC18, 5 μm, 30×50 mm). A fraction containing the material of interest was neutralized with solid-supported tetraalkyl ammonium carbonate (Polymer Laboratories, PL-HCO3 MP-Resin) to yield (S)-4-amino-19,21-dimethyl-10,17-dioxo-7-thia-3,5,11,16-tetraazatricyclo[16.3.1.12,6]tricosa-1(21),2,4,6(23),18(22),19-hexaene-12-carboxylic acid (2-hydroxyethyl) amide (Compound 46) (7 mg) was obtained as a white solid material.

Workup

  1. stirringstirred for 1.5 hours
  2. extractionThe solution was extracted four times with ethyl acetate (20 ml)
  3. dry with materialdried over anhydrous sodium sulfate
  4. customAfter the inorganic salt was removed by filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customto give crude product (39 mg)
  7. customat 0° C
  8. stirringAfter stirring at 0° C. for 30 minutes
  9. temperaturethe mixture was warmed to room temperature
  10. stirringstirred for 30 minutes
  11. concentrationThe reaction solution was concentrated under reduced pressure
  12. customThe resulting crude product was purified by high performance liquid chromatography (
  13. customB, 1% (0 min)→1% (1 min)→30% (7 min)→95% (8 min)→95% (9 min)→1% (10 min)
  14. additionA fraction containing the material of interest

Sources & evidence

ORD record
ord-3f4de57fd3ee4eeb90146e16f7e5d6de
Source dataset
uspto-grants-2013_01
Patent number
US08362236B2

Reaction notes

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