Hydrochloric Acid → (R)-1-((1,6-diethyl-4-((tetrahydro-2H-pyran-4-yl)amino)-1H-pyrazolo[3,4-b]pyridin-5-yl)methyl)-3-(4-(4-((6-((2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl)amino)hexyl)oxy)butyl)phenyl)urea

HRID 385291Notes

Reaction equation

HRID 385291 reaction equation
C(OC([O:8][C:9]1[CH:18]=[CH:17][C:16]2[C:11](=[C:12]([O:79]C(OC(C)(C)C)=O)[CH:13]=[CH:14][C:15]=2[C@@H:19]([O:71][Si](C(C)(C)C)(C)C)[CH2:20][N:21]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][O:35][CH2:36][CH2:37][CH2:38][CH2:39][C:40]2[CH:45]=[CH:44][C:43]([NH:46][C:47]([NH:49][CH2:50][C:51]3[C:52]([NH:64][CH:65]4[CH2:70][CH2:69][O:68][CH2:67][CH2:66]4)=[C:53]4[CH:61]=[N:60][N:59]([CH2:62][CH3:63])[C:54]4=[N:55][C:56]=3[CH2:57][CH3:58])=[O:48])=[CH:42][CH:41]=2)C(=O)OC(C)(C)C)[N:10]=1)=O)(C)(C)C.Cl>CO>[CH2:62]([N:59]1[C:54]2=[N:55][C:56]([CH2:57][CH3:58])=[C:51]([CH2:50][NH:49][C:47]([NH:46][C:43]3[CH:44]=[CH:45][C:40]([CH2:39][CH2:38][CH2:37][CH2:36][O:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][CH2:29][NH:21][CH2:20][C@H:19]([OH:71])[C:15]4[CH:14]=[CH:13][C:12]([OH:79])=[C:11]5[C:16]=4[CH:17]=[CH:18][C:9](=[O:8])[NH:10]5)=[CH:41][CH:42]=3)=[O:48])[C:52]([NH:64][CH:65]3[CH2:70][CH2:69][O:68][CH2:67][CH2:66]3)=[C:53]2[CH:61]=[N:60]1)[CH3:63]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86659067(R)-tert-butyl (2-(2,8-bis((tert-butoxycarbonyl)oxy)quinolin-5-yl)-2-((tert-butyldimethylsilyl)oxy)ethyl)(6-(4-(4-(3-((1,6-diethyl-4-((tetrahydro-2H-pyran-4-yl)amino)-1H-pyrazolo[3,4-b]pyridin-5-yl)methyl)ureido)phenyl)butoxy)hexyl)carbamate

Product 1

HCID 54588887(R)-1-((1,6-diethyl-4-((tetrahydro-2H-pyran-4-yl)amino)-1H-pyrazolo[3,4-b]pyridin-5-yl)methyl)-3-(4-(4-((6-((2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl)amino)hexyl)oxy)butyl)phenyl)urea

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The crude concentrated reaction mixture containing Intermediate 57 was taken up in methanol (approximately 0.50 mL) and treated with a solution of hydrogen chloride in dioxanes (4 N, 2 mL). The mixture was subsequently concentrated to dryness under reduced pressure. The residue was purified by reverse-phase high performance liquid chromatography (RP-HPLC, acetonitrile/water/0.1% TFA) to provide, after concentration, the trifluoroacetic acid salt of the title compound as a powder (107 mg, 58% over two steps).

Workup

  1. concentrationThe crude concentrated
  2. customreaction mixture
  3. concentrationThe mixture was subsequently concentrated to dryness under reduced pressure
  4. customThe residue was purified by reverse-phase high performance liquid chromatography (RP-HPLC, acetonitrile/water/0.1% TFA)
  5. customto provide
  6. concentrationafter concentration

Sources & evidence

ORD record
ord-2cb03e95e7d64e438425d95612032fe1
Source dataset
uspto-grants-2013_02
Patent number
US08367829B2

Reaction notes

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