Triethylamine → HCID 67494748, compound

HRID 2047231Notes

Reaction equation

HRID 2047231 reaction equation
C[Si](C)(C)CCOCN(COCC[Si](C)(C)C)[C:8]1[N:13]2[N:14]=[CH:15][C:16]([C:17]3[CH:18]=[N:19][C:20]4[C:25]([CH:26]=3)=[CH:24][C:23]([F:27])=[CH:22][CH:21]=4)=[C:12]2[N:11]=[C:10]([N:28]([CH2:36][CH:37]2[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]2)C(=O)OC(C)(C)C)[CH:9]=1.[CH3:53][N:54]=[C:55]=[O:56].[CH2:57]([N:59](CC)CC)C.[Cl-].[NH4+:65]>ClCCl>[NH2:65][C:8]1[N:13]2[N:14]=[CH:15][C:16]([C:17]3[CH:18]=[N:19][C:20]4[C:25]([CH:26]=3)=[CH:24][C:23]([F:27])=[CH:22][CH:21]=4)=[C:12]2[N:11]=[C:10]([NH:28][CH2:36][CH:37]2[CH2:42][CH2:41][N:40]([C:55]([NH:54][CH3:53])=[O:56])[CH2:39][CH2:38]2)[C:9]=1[C:57]#[N:59]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 12228Methyl IsocyanateHCID 25517Ammonium ChlorideHCID 66733694HCID 66733694, compound

Product 1

HCID 67494748HCID 67494748, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Compound, tert-butyl 7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-fluoroquinolin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl(piperidin-4-ylmethyl)carbamate (1 equiv) was stirred in a mixture of methyl isocyanate (1.1 equiv), and triethylamine (1.5 equiv) in dichloromethane at 0° C. until the reaction was deemed complete by TLC, HPLC, or LC-MS analysis. The reaction mixture was poured into saturated aqueous ammonium chloride, and then extracted twice with dichloromethane. The combined organics were dried over sodium sulfate, filtered, concentrated, and purified on silica gel to give the desired product. This material (1 equiv) and NBS (1.05 equiv) in acetonitrile was stirred at room temperature until the reaction was deemed complete by HPLC, LC-MS, or TLC analysis. The reaction mixture was concentrated, re-dissolved in dichloromethane, washed with saturated aqueous sodium thiosulfate, dried over sodium sulfate, filtered, concentrated, and purified on silica gel. The resulting material was stirred with the palladium catalysts (0.2 equiv each) and stannane (1.5 equiv) in dioxane at 160° C. until the reaction was deemed complete by HPLC, LC-MS, or TLC analysis. The reaction was allowed to cool to room temperature, diluted with ethyl acetate, washed with brine, dried over sodium sulfate, filtered, concentrated, and purified in silica gel. The resulting material was stirred in TFA and water at room temperature until the reaction was deemed complete by HPLC, LC-MS, or TLC analysis. The mixture was concentrated, purified by prep-HPLC, and freeze-dried to afford compound 4-((7-amino-6-cyano-3-(6-fluoroquinolin-3-yl)pyrazolo[1,5-a]pyrimidin-5-ylamino)methyl)-N-methylpiperidine-1-carboxamide.

Workup

  1. extractionextracted twice with dichloromethane
  2. dry with materialThe combined organics were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. custompurified on silica gel

Sources & evidence

ORD record
ord-549491ce1818412f957ab2a33af01bea
Source dataset
uspto-grants-2013_11
Patent number
US08591943B2

Reaction notes

Loading…