2-Pyridinemethanamine → HCID 90386205, compound

HRID 2170149Notes

Reaction equation

HRID 2170149 reaction equation
[C:1]([NH:5][S:6]([C:9]1[S:10][CH:11]=[C:12]([C:14]2[N:19]=[C:18](O)[C:17]3=[C:21]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[CH:22]=[CH:23][N:16]3[N:15]=2)[N:13]=1)(=[O:8])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN([P+](O[N:41]1N=[N:48][C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][C:42]1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.C1CCN2C(=NCCC2)CC1.N1C=CC=CC=1CN>C(#N)C.O>[C:1]([NH:5][S:6]([C:9]1[S:10][CH:11]=[C:12]([C:14]2[N:19]=[C:18]([NH:41][CH2:42][C:47]3[CH:46]=[CH:45][CH:44]=[CH:43][N:48]=3)[C:17]3=[C:21]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[CH:22]=[CH:23][N:16]3[N:15]=2)[N:13]=1)(=[O:8])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 195092-PyridinemethanamineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 178449990HCID 178449990, compound

Product 1

HCID 90386205HCID 90386205, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

N-(tert-Butyl)-4-(4-hydroxy-5-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)thiazole-2-sulfonamide (0.0600 g, 0.140 mmol) was dissolved in acetonitrile (5 mL) and cooled to 0° C. BOP reagent (0.0620 g, 0.140 mmol) was added slowly, followed by DBU (0.0210 mL, 0.140 mmol). The reaction mixture was allowed to reach ambient temperature for 1 h then cooled to 0° C. Pyridin-2-ylmethanamine was added, (0.0150 g, 0.140 mmol). The reaction mixture was allowed to reach ambient temperature and stir for 14 h and diluted with water. The aqueous mixture was extracted with ethyl acetate (3×10 mL). The combined organic extracts were dried with anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The residue was purified by column chromatography using CombiFlash (REDISEP®, silica gel, 40 g, 1.2% methanol in CH2Cl2) to afford N-(tert-butyl)-4-(5-phenyl-4-((pyridin-2-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)thiazole-2-sulfonamide (0.0400 g, 55.0%). The impure compound was taken to the next step as such. LCMS Condition B-13: retention time 2.13 min, [M+1]=520.2.

Workup

  1. temperaturethen cooled to 0° C
  2. customto reach ambient temperature
  3. extractionThe aqueous mixture was extracted with ethyl acetate (3×10 mL)
  4. dry with materialThe combined organic extracts were dried with anhydrous sodium sulfate
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-4cccdc3a3fcf46dfaffdc06964542f36
Source dataset
uspto-grants-2015_06
Patent number
US09050345B2

Reaction notes

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