Benzylamine → HCID 136138779, compound

HRID 2365428Notes

Reaction equation

HRID 2365428 reaction equation
[Cl:1]C1C=C(C=CC=1)C(O)=O.[Cl:11][C:12]1[CH:13]=[C:14]([C:18]2[CH:22]=[N:21][NH:20][C:19]=2[C:23]2[C:31]3[C:26](=[N+:27]([O-])[CH:28]=[CH:29][CH:30]=3)[NH:25][CH:24]=2)[CH:15]=[CH:16][CH:17]=1.CCN(C(C)C)C(C)C.[CH2:42]([NH2:49])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.Cl.CO>CN(C=O)C.CCOC(C)=O>[ClH:1].[ClH:11].[CH2:42]([NH:49][C:28]1[N:27]=[C:26]2[NH:25][CH:24]=[C:23]([C:19]3[NH:20][N:21]=[CH:22][C:18]=3[C:14]3[CH:15]=[CH:16][CH:17]=[C:12]([Cl:11])[CH:13]=3)[C:31]2=[CH:30][CH:29]=1)[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1

Participants

8

Reactant 5

HCID 7504BenzylamineHCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 21893726Hydrochloride methanolHCID 178524356HCID 178524356, compound

Product 1

HCID 136138779HCID 136138779, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3-[4-(3-chlorophenyl)-2H-pyrazol-3-yl]-1H-pyrrolo[2,3-b]pyridine 7-oxide meta-chlorobenzoate salt (93 mg, 0.2 mmol), DIPEA (104 mg, 0.8 mmol) and benzylamine (45 mg, 0.4 mmol) in DMF was treated with PyBrOP (186 mg, 0.4 mmol) and the resulting solution stirred at room temperature overnight. After this time the reaction was diluted with EtOAc (150 ml) and washed with saturated sodium bicarbonate solution (2×50 mL) followed by saturated sodium chloride solution (50 mL). The organic layer was then dried over sodium sulfate and concentrated. The residue was purified by column chromatography (SiO2, 40-100% EtOAc in hexanes) followed by further purification by preparative TLC (SiO2, EtOAc). The resulting material was then combined with material obtained from a previous reaction, run under identical conditions, and the combined product treated with 1N HCl/MeOH (1:1, 5 mL). The resulting solution was then concentrated and the residue re-dissolved in water (5 mL). Subsequent isolation by lyophilization afforded the title compound as a white solid in 9% overall yield.

Workup

  1. washwashed with saturated sodium bicarbonate solution (2×50 mL)
  2. dry with materialThe organic layer was then dried over sodium sulfate
  3. concentrationconcentrated
  4. customThe residue was purified by column chromatography (SiO2, 40-100% EtOAc in hexanes)
  5. customfollowed by further purification by preparative TLC (SiO2, EtOAc)
  6. customobtained from a previous reaction
  7. concentrationThe resulting solution was then concentrated
  8. dissolutionthe residue re-dissolved in water (5 mL)

Sources & evidence

ORD record
ord-47cb71414fd043bf9f3a47539a1d12f2
Source dataset
uspto-grants-2014_04
Patent number
US08697697B2

Reaction notes

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