Hydrochloric Acid → [4-(7-Amino-6-cyano-3-quinolin-3-yl-pyrazolo[1,5-a]pyrimidin-5-yl)-cyclohexyl]-acetic acid

HRID 2047068Notes

Reaction equation

HRID 2047068 reaction equation
C([O:3][C:4](=[O:49])[CH2:5][CH:6]1[CH2:11][CH2:10][CH:9]([C:12]2[C:17](Br)=[C:16]([N:19](COCC[Si](C)(C)C)COCC[Si](C)(C)C)[N:15]3[N:36]=[CH:37][C:38]([C:39]4[CH:40]=[N:41][C:42]5[C:47]([CH:48]=4)=[CH:46][CH:45]=[CH:44][CH:43]=5)=[C:14]3[N:13]=2)[CH2:8][CH2:7]1)C.[Sn]([C:63]#[N:64])(CCCC)(CCCC)CCCC.Cl>O1CCOCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[NH2:19][C:16]1[N:15]2[N:36]=[CH:37][C:38]([C:39]3[CH:40]=[N:41][C:42]4[C:47]([CH:48]=3)=[CH:46][CH:45]=[CH:44][CH:43]=4)=[C:14]2[N:13]=[C:12]([CH:9]2[CH2:10][CH2:11][CH:6]([CH2:5][C:4]([OH:3])=[O:49])[CH2:7][CH2:8]2)[C:17]=1[C:63]#[N:64]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 200512Stannanecarbonitrile, tributyl-HCID 66733730(4-{7-[Bis-(2-trimethylsilanyl-ethoxymethyl)-amino]-6-bromo-3-quinolin-3-yl-pyrazolo[1,5-a]pyrimidin-5-yl}-cyclohexyl)-acetic acid ethyl ester

Product 1

HCID 67494440[4-(7-Amino-6-cyano-3-quinolin-3-yl-pyrazolo[1,5-a]pyrimidin-5-yl)-cyclohexyl]-acetic acidYield 26.5%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A degassed mixture of (4-{7-[bis-(2-trimethylsilanyl-ethoxymethyl)-amino]-6-bromo-3-quinolin-3-yl-pyrazolo[1,5-a]pyrimidin-5-yl}-cyclohexyl)-acetic acid ethyl ester (0.078 mmol, 60 mg), Bu3SnCN (50 mg, 0.156 mmoL), Pd[P(t-Bu)3]2 (8.3 mg, 0.016 mmoL) in Dioxane (1 mL) was heated at 100° C. for 18 h. The reaction mixture was concentrated in vacuo. The crude mixture was dissolved in 2:1 MeOH:H2O (1.5 mL) and was treated with 2N NaOH(aq) (0.5 mL). The resulting reaction mixture was stirred at room temperature for 18 hours. Aqueous hydrochloride solution (1.0 N, 2 ml) was added to the reaction mixture and the resulting solution was stirred at 65° C. for 2 h. The solution was concentrated and purified by prep-LC to afford the title compound (8.8 mg) as a mixture of cis and trans isomers: LC/MS RT=3.88 min. Mass calculated for, M+H 427.18, observed 427.18.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionThe crude mixture was dissolved in 2:1 MeOH
  3. additionH2O (1.5 mL) and was treated with 2N NaOH(aq) (0.5 mL)
  4. customThe resulting reaction mixture
  5. stirringthe resulting solution was stirred at 65° C. for 2 h
  6. concentrationThe solution was concentrated
  7. custompurified by prep-LC

Sources & evidence

ORD record
ord-c7aa11796fef4a6fb7d83cfd1c976a04
Source dataset
uspto-grants-2013_11
Patent number
US08591943B2

Reaction notes

Loading…