Aniline → HCID 86678991, compound

HRID 2203356Notes

Reaction equation

HRID 2203356 reaction equation
C[Al](C)C.[NH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[NH2:12][C:13]1[C:14]2[C:40]([CH3:46])([C:41](OCC)=[O:42])[C:39](=[O:47])[NH:38][C:15]=2[N:16]=[C:17]([C:19]2[C:27]3[C:22](=[CH:23][C:24]([Cl:28])=[CH:25][CH:26]=3)[N:21]([CH2:29][CH2:30][C:31]([F:37])([F:36])[C:32]([F:35])([F:34])[F:33])[N:20]=2)[N:18]=1.C(C(C(C([O-])=O)O)O)([O-])=O.[K+].[Na+]>CCOC(C)=O.C1(C)C=CC=CC=1>[NH2:12][C:13]1[C:14]2[C:40]([CH3:46])([C:41]([NH:5][C:6]3[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=3)=[O:42])[C:39](=[O:47])[NH:38][C:15]=2[N:16]=[C:17]([C:19]2[C:27]3[C:22](=[CH:23][C:24]([Cl:28])=[CH:25][CH:26]=3)[N:21]([CH2:29][CH2:30][C:31]([F:36])([F:37])[C:32]([F:35])([F:33])[F:34])[N:20]=2)[N:18]=1

Participants

7

Reactant 4

HCID 6115AnilineHCID 9855836Potassium sodium tartarateHCID 16682925TrimethylaluminumHCID 86678985HCID 86678985, compound

Product 1

HCID 86678991HCID 86678991, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Trimethylaluminum (2.0 M in toluene, 1.2 mL, 2.4 mmol) was added to a toluene (8 mL) solution of aniline (248 mg, 2.66 mmol). After stirring at room temperature for 2 hours, solid ethyl 4-amino-2-[6-chloro-1-(3,3,4,4,4-pentafluorobutyl)-1H-indazol-3-yl]-5-methyl-6-oxo-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-5-carboxylate, as described in Example 157, (250 mg, 0.469 mmol) was added. The reaction solution was stirred at 50° C. for 30 minutes and then at room temperature overnight. Sodium potassium tartrate (0.5M aqueous, 25 mL) and EtOAc (25 mL) were added and the mixture stirred vigorously for 30 minutes. The phases were separated and the organic phase was washed with water (2×) and brine. The organic phase was then dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography using a hexanes/EtOAc gradient to give the indicated product. Chiral separation using SFC on a Chiralpak AD-H column provided both enantiomers of the title compound. 1H NMR (400 MHz, CH3CN-d3): δ 9.19 (s, 1H); 8.55 (d, J=8.69 Hz, 1H); 7.64 (s, 1H); 7.55 (d, J=8.01 Hz, 2H); 7.32 (t, J=7.77 Hz, 2H); 7.20-7.10 (m, 2H); 6.45 (s, 2H); 4.72 (t, J=7.10 Hz, 2H); 2.85-2.69 (m, 2H); 1.79 (s, 3H). m/z=580.2 (M+H).

Workup

  1. additionwas added
  2. stirringThe reaction solution was stirred at 50° C. for 30 minutes
  3. customat room temperature
  4. customovernight
  5. stirringthe mixture stirred vigorously for 30 minutes
  6. customThe phases were separated
  7. washthe organic phase was washed with water (2×) and brine
  8. dry with materialThe organic phase was then dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by silica gel chromatography
  12. customto give the indicated product
  13. customChiral separation

Sources & evidence

ORD record
ord-78eb62dfc74546b7b9474aff265e9304
Source dataset
uspto-grants-2016_06
Patent number
US09365574B2

Reaction notes

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