Trifluoroacetic acid → HCID 178464312, compound

HRID 2274428Notes

Reaction equation

HRID 2274428 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH2:8]([N:10]([CH2:43][CH3:44])[C:11]([NH:13][C:14]1[C:15]([C:25]2[NH:29][C:28]3[CH:30]=[C:31]([N:35]4[CH2:41][CH2:40][CH2:39][N:38]([CH3:42])[CH2:37][CH2:36]4)[C:32]([F:34])=[CH:33][C:27]=3[N:26]=2)=[N:16][N:17](C2CCCCO2)[CH:18]=1)=[O:12])[CH3:9]>ClCCl>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH2:43]([N:10]([CH2:8][CH3:9])[C:11]([NH:13][C:14]1[C:15]([C:25]2[NH:29][C:28]3[CH:30]=[C:31]([N:35]4[CH2:41][CH2:40][CH2:39][N:38]([CH3:42])[CH2:37][CH2:36]4)[C:32]([F:34])=[CH:33][C:27]=3[N:26]=2)=[N:16][NH:17][CH:18]=1)=[O:12])[CH3:44]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 178464301HCID 178464301, compound

Product 1

HCID 178464312HCID 178464312, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
22 °C

Procedure

0.5 mL of trifluoroacetic acid is added to a solution of 39 mg of 1,1-diethyl-3-[3-[5-fluoro-6-(4-methylperhydro-1,4-diazepin-1-yl)-1H-benzimidazol-2-yl]-1-(tetrahydropyran-2-yl)-1H-pyrazol-4-yl}urea in solution in 1 mL of dichloromethane. The reaction medium is stirred at 22° C. for 16 hours. The reaction medium is concentrated under vacuum in a rotary evaporator. After evaporation, the reaction crude is purified by flash chromatography on an Intelliflash apparatus on an Analogix RS-4 cartridge. The elution is carried out with pure dichloromethane and then with dichloromethane containing 5% of ammoniacal methanol. 12 mg of 1,1-diethyl-3-{3-[5-fluoro-6-(4-methylperhydro-1,4-diazepin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl}urea trifluoroacetate salt are obtained in the form of a black resin. 1H NMR (300 MHz, DMSO-d6, δ in ppm): 1.10 (t, J=7.0 Hz, 6H); 2.20 (broad m, 2H); 2.89 (s, 3H); from 3.07 to 3.68 (m, 8H); 3.34 (q, J=7.0 Hz, 4H); 7.22 (d, J=7.5 Hz, 1H); 7.55 (d, J=12.0 Hz, 1H); 7.96 (s, 1H). EI mass spectrum: m/z=428 M+., m/z=355 (M−C4H11N)+, m/z=69 CF3+ (relative to TFA), m/z=58 C3H8N+ (base peak), m/z=45 CO2H+ (relative to TFA).

Workup

  1. concentrationThe reaction medium is concentrated under vacuum in a rotary evaporator
  2. customAfter evaporation
  3. customthe reaction crude
  4. customis purified by flash chromatography on an Intelliflash apparatus on an Analogix RS-4 cartridge
  5. washThe elution

Sources & evidence

ORD record
ord-2d9bbf59bc1546d380574ea1d9df6d3e
Source dataset
uspto-grants-2015_09
Patent number
US09126969B2

Reaction notes

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