Trifluoroacetic acid → HCID 67700761, compound

HRID 626778Notes

Reaction equation

HRID 626778 reaction equation
C(O)(C(F)(F)F)=O.C(OC(=O)[NH:14][C:15]1[CH:20]=[C:19]([NH:21][C:22]2[C:27]3=[CH:28][N:29]([C:31]4[C:36]([Cl:37])=[CH:35][CH:34]=[CH:33][C:32]=4[Cl:38])[N:30]=[C:26]3[C:25]([CH3:39])=[CH:24][N:23]=2)[N:18]=[CH:17][N:16]=1)(C)(C)C>C(Cl)Cl>[Cl:38][C:32]1[CH:33]=[CH:34][CH:35]=[C:36]([Cl:37])[C:31]=1[N:29]1[CH:28]=[C:27]2[C:22]([NH:21][C:19]3[CH:20]=[C:15]([NH2:14])[N:16]=[CH:17][N:18]=3)=[N:23][CH:24]=[C:25]([CH3:39])[C:26]2=[N:30]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 89809321HCID 89809321, compound

Product 1

HCID 67700761HCID 67700761, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (1.5 mL) was slowly added to the crude mixture of {6-[2-(2,6-dichlorophenyl)-7-methyl-2H-pyrazolo[4,3-c]pyridin-4-ylamino]-pyrimidin-4-yl}-bis-carbamic acid tert-butyl ester and {6-[2-(2,6-dichlorophenyl)-7-methyl-2H-pyrazolo[4,3-c]pyridin-4-ylamino]-pyrimidin-4-yl}-carbamic acid tert-butyl ester in DCM (1.5 mL) at 0° C., under an atmosphere of nitrogen. The reaction mixture was stirred with warming to room temperature over 2 hours. The resultant mixture was concentrated under reduced pressure and the residue was triturated with diethyl ether. The pale yellow solid formed was filtered and washed with diethyl ether to afford the crude title compound (30 mg). The filtrate was concentrated under reduced pressure to afford impure title compound as an yellow oil (220 mg). The two batches were separately dissolved in ethyl acetate, then combined and washed with saturated aqueous sodium bicarbonate solution. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated to afford the crude residue. This was purified by silica gel flash chromatography (0-10% methanol in DCM), then further purified by HPLC (gradient: 5 to 98% acetonitrile (0.1% ammonium hydroxide) in water (0.1% ammonium hydroxide)], to afford the title compound as a white powder (14 mg, 14% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.38 (s, 1H), 8.51 (d, J=0.9 Hz, 1H), 7.89-7.85 (m, 2H), 7.81-7.74 (m, 2H), 6.51 (br s, 1H), 2.45 (d, J=1.3 Hz, 3H). LCMS (Method B): RT=3.05 min, m/z: 386 [M+H+].

Workup

  1. concentrationThe resultant mixture was concentrated under reduced pressure
  2. customthe residue was triturated with diethyl ether
  3. customThe pale yellow solid formed
  4. filtrationwas filtered
  5. washwashed with diethyl ether
  6. customto afford the crude title compound (30 mg)
  7. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-8b268a688d4046b98102c6de9290efe6
Source dataset
uspto-grants-2016_04
Patent number
US09309240B2

Reaction notes

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