Trifluoroacetic acid → HCID 59304358, compound

HRID 2241339Notes

Reaction equation

HRID 2241339 reaction equation
COC1C=CC(C[N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:23]=[CH:22][C:21]([NH:24][C:25]([C:27]5[C:28](=[O:40])[N:29]([C:33]6[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=6)[N:30]=[CH:31][CH:32]=5)=[O:26])=[CH:20][C:19]=4[F:41])=[C:11]3[C:10]([N:42]3[CH2:46][CH2:45][C@H:44]([N:47]([CH3:49])[CH3:48])[CH2:43]3)=[N:9]2)=CC=1.C(O)(C(F)(F)F)=O>>[CH3:48][N:47]([CH3:49])[C@H:44]1[CH2:45][CH2:46][N:42]([C:10]2[C:11]3[C:12](=[N:13][CH:14]=[CH:15][C:16]=3[O:17][C:18]3[CH:23]=[CH:22][C:21]([NH:24][C:25]([C:27]4[C:28](=[O:40])[N:29]([C:33]5[CH:34]=[CH:35][C:36]([F:39])=[CH:37][CH:38]=5)[N:30]=[CH:31][CH:32]=4)=[O:26])=[CH:20][C:19]=3[F:41])[NH:8][N:9]=2)[CH2:43]1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68513136HCID 68513136, compound

Product 1

HCID 59304358HCID 59304358, compound

Conditions

Temperature
50 °C

Procedure

To a flask containing (S)—N-(4-(1-(4-methoxybenzyl)-3-(3-(dimethylamino)pyrrolidin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide (14 mg, 0.02 mmol) at ambient temperature under a drying tube was added TFA (1 mL), and the reaction mixture was heated at 50° C. overnight. After cooling, the reaction was concentrated to dryness and then redissolved in 5 mL dichloromethane, to which 5 mL of 10% sodium carbonate was added. After stirring for a few minutes, the layers were separated and the organics were washed with 10% sodium carbonate. The organics were dried (MgSO4), filtered and concentrated to a crude oil. Biotage 12S with step gradient of dichloromethane (100 mL), 5/95 MeOH/dichloromethane (100 mL), and 9/1 dichloromethane/MeOH (200 mL) eluted the product. The product containing fractions were pooled and concentrated to a yellow solid (4.2 mg, 36%). 1H NMR (400 MHz, CDCl3) δ 11.83 (br s, 1H), 8.41 (d, 1H), 8.23 (m, 1H), 7.96 (m, 1H), 7.60 (m, 2H), 7.40 (m, 1H), 7.24 (m, 2H), 6.16 (d, 1H), 3.82 (m, 1H), 3.72 (m, 2H), 3.56 (m, 1H), 2.87 (m, 1H), 2.30 (s, 6H), 2.20 (m, 1H), 1.94 (m, 1H). LCMS (APCI+): m/z 573 (M+1) detected.

Workup

  1. temperatureAfter cooling
  2. concentrationthe reaction was concentrated to dryness
  3. dissolutionredissolved in 5 mL dichloromethane, to which 5 mL of 10% sodium carbonate
  4. additionwas added
  5. customthe layers were separated
  6. washthe organics were washed with 10% sodium carbonate
  7. dry with materialThe organics were dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated to a crude oil
  10. washBiotage 12S with step gradient of dichloromethane (100 mL), 5/95 MeOH/dichloromethane (100 mL), and 9/1 dichloromethane/MeOH (200 mL) eluted the product
  11. additionThe product containing fractions
  12. concentrationconcentrated to a yellow solid (4.2 mg, 36%)

Sources & evidence

ORD record
ord-4d314e72beb04c1390d5f059887570c0
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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