HCID 131734501, compound → HCID 73505858, compound

HRID 590881Notes

Reaction equation

HRID 590881 reaction equation
O[C:2]([C:4](F)(F)F)=[O:3].COC(=O)[CH:11]([NH:18][C:19]([NH:21][C:22]1[N:27]=[CH:26][C:25]2[C:28]([NH:31][CH2:32][CH3:33])=[N:29][NH:30][C:24]=2[CH:23]=1)=[O:20])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[CH3:35][Mg]Br>C1COCC1>[CH2:32]([NH:31][C:28]1[C:25]2[CH:26]=[N:27][C:22]([NH:21][C:19]([NH:18][CH:11]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:2]([OH:3])([CH3:4])[CH3:35])=[O:20])=[CH:23][C:24]=2[NH:30][N:29]=1)[CH3:33]

Participants

4

Reactant 2

HCID 131734501HCID 131734501, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 73505858HCID 73505858, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To the solution of (S)-methyl 2-(3-(3-((tert-butoxycarbonyl)(ethyl)amino)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)ureido)-2-phenylacetate (0.078 g, 0.109 mmol) in anhydrous CH2Cl2 (1 mL) was added TFA (imp followed by Et3SiH (2 drops). The resultant mixture was stirred at ambient temperature. After 2 h of stirring, solvent was removed under reduced pressure, the residue (TFA salt) thus obtained was triturated in diethyl ether to afford the compound which was taken as such for next step. At 0° C., to the solution of [3-(3-Ethylamino-1H-pyrazolo[4,3-c]pyridin-6-yl)-ureido]-phenyl-acetic acid methyl ester TFA salt (0.06 g, 0.163 mmol) in anhydrous THF was added methyl magnesium bromide (1 M solution in toluene, 1.63 mL, 1.63 mmol) and resultant mixture was allowed to warm and stirred at ambient temperature. After 10 h, the reaction was quenched with saturated aqueous NH4Cl solution (5 mL), and the organic contents were extracted with CH2Cl2 (3×10 mL). The volatiles were removed under reduced pressure and the residue thus obtained was further purified by prep HPLC to afford the title compound. 1H NMR (ppm, 400 MHz, CD3OD): δ 8.69 (s, 1H), 7.44-7.39 (m, 2H), 7.33-7.29 (m, 2H), 7.26-7.23 (m, 1H), 6.99 (s, 1H), 4.78 (s, 1H), 3.36 (q, J=7.2 Hz, 2H), 1.31 (t, J=7.1 Hz, 3H), 1.30 (s, 3H), 1.16 (s, 3H). MS ESI calc'd. for C19H24N6O2 [M+H]+ 369. Found 369.

Workup

  1. customwas triturated in diethyl ether
  2. customto afford the compound which
  3. temperatureto warm
  4. customthe reaction was quenched with saturated aqueous NH4Cl solution (5 mL)
  5. extractionthe organic contents were extracted with CH2Cl2 (3×10 mL)
  6. customThe volatiles were removed under reduced pressure
  7. customthe residue thus obtained
  8. customwas further purified by prep HPLC

Sources & evidence

ORD record
ord-8eca01fa90454225bd026e40f46b669c
Source dataset
uspto-grants-2016_01
Patent number
US09233979B2

Reaction notes

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