Hydrochloric Acid → 7-(1H-indazol-5-ylamino)-2-methyl-1-(3-methylbutyl)-4-phenyl-1,4-dihydropyrido[3,4-b]pyrazin-3(2H)-one

HRID 530133Notes

Reaction equation

HRID 530133 reaction equation
[CH3:1][CH:2]1[C:7](=[O:8])[N:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:5]2[CH:15]=[N:16][C:17]([NH:19][C:20]3[CH:21]=[C:22]4[C:26](=[CH:27][CH:28]=3)[N:25](C3CCCCO3)[N:24]=[CH:23]4)=[CH:18][C:4]=2[N:3]1[CH2:35][CH2:36][CH:37]([CH3:39])[CH3:38].Cl.ClCCl>O1CCOCC1>[NH:25]1[C:26]2[C:22](=[CH:21][C:20]([NH:19][C:17]3[N:16]=[CH:15][C:5]4[N:6]([C:9]5[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=5)[C:7](=[O:8])[CH:2]([CH3:1])[N:3]([CH2:35][CH2:36][CH:37]([CH3:38])[CH3:39])[C:4]=4[CH:18]=3)=[CH:28][CH:27]=2)[CH:23]=[N:24]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 6344DichloromethaneHCID 895704012-methyl-1-(3-methylbutyl)-4-phenyl-7-{[1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl]amino}-1,4-dihydropyrido[3,4-b]pyrazin-3(2H)-one

Product 1

HCID 895704027-(1H-indazol-5-ylamino)-2-methyl-1-(3-methylbutyl)-4-phenyl-1,4-dihydropyrido[3,4-b]pyrazin-3(2H)-oneYield 60%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of 2-methyl-1-(3-methylbutyl)-4-phenyl-7-{[1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl]amino}-1,4-dihydropyrido[3,4-b]pyrazin-3(2H)-one (15 mg) in dioxane (2 mL) was added 2N aq. HCl (2 mL) at rt. The resulting mixture was stirred at rt for 2 h. LC-MS indicated completion of reaction. Dichloromethane (30 mL) was added to the reaction mixture, the organic phase was washed with aq. NaHCO3, dried over anhydrous sodium sulfate, and evaporated to give a residue, which was purified by preparative Thin-Layer Chromatography (developing solvent: 2% methanol in dichloromethane) to give the desired product (yield: 60%) 1H NMR (400 MHz, CD3OD) b 0.88 (d, J=6.4 Hz, 3H), 0.95 (d, J=6.4 Hz, 3H), 1.41 (d, J=6.82 Hz, 3H), 1.55-1.65 (m, 3H), 3.18-3.28 (m, 1H), 3.39-3.49 (m, 1H), 4.26 (q, J=6.74 Hz, 1H), 6.10 (s, 1H), 6.79 (s, 1H), 7.27-7.34 (m, 3H), 7.49-7.55 (m, 2H), 7.56-7.62 (m, 2H), 7.75 (d, J=1.52 Hz, 1H), 7.97 (s, 1H). MS(ES+): m/z 441.19 [MH+]. HPLC: tR=2.55 (ZQ3, Polar_5 min).

Workup

  1. customcompletion of reaction
  2. washthe organic phase was washed with aq. NaHCO3
  3. dry with materialdried over anhydrous sodium sulfate
  4. customevaporated
  5. customto give a residue, which
  6. customwas purified by preparative Thin-Layer Chromatography (developing solvent: 2% methanol in dichloromethane)

Sources & evidence

ORD record
ord-a8e3a32379384a228308f8f90529998d
Source dataset
uspto-grants-2016_05
Patent number
US09351974B2

Reaction notes

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