Hydrochloric Acid → HCID 86679008, compound

HRID 2203371Notes

Reaction equation

HRID 2203371 reaction equation
C[Mg]Br.[CH2:4]1COCC1.[NH2:9][C:10]1[C:11]2[C:37]([CH3:44])([C:38]([NH:40][CH:41]3[CH2:43][CH2:42]3)=[O:39])[C:36](=[O:45])[NH:35][C:12]=2[N:13]=[C:14]([C:16]2[C:24]3[C:19](=[N:20][C:21](Cl)=[CH:22][CH:23]=3)[N:18]([CH2:26][CH2:27][C:28]([F:34])([F:33])[C:29]([F:32])([F:31])[F:30])[N:17]=2)[N:15]=1.Cl>CN1C(=O)CCC1>[NH2:9][C:10]1[C:11]2[C:37]([CH3:44])([C:38]([NH:40][CH:41]3[CH2:43][CH2:42]3)=[O:39])[C:36](=[O:45])[NH:35][C:12]=2[N:13]=[C:14]([C:16]2[C:24]3[C:19](=[N:20][C:21]([CH3:4])=[CH:22][CH:23]=3)[N:18]([CH2:26][CH2:27][C:28]([F:34])([F:33])[C:29]([F:32])([F:31])[F:30])[N:17]=2)[N:15]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 86679007HCID 86679007, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 86679008HCID 86679008, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Methylmagnesium bromide (0.42 ml, 0.584 mmol, 1.4 M in THF) was added to a THF (1.2 ml) and NMP (0.3 ml) solution containing 4-amino-2-(6-chloro-1-(3,3,4,4,4-pentafluorobutyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-N-cyclopropyl-5-methyl-6-oxo-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-5-carboxamide, as described in Example 176, (53 mg, 0.097 mmol) and iron(111) acetylacetonate (34.4 mg, 0.097 mmol). After stirring at rt for 30 min. the reaction mixture was adjusted to pH 7 with 1N HCl at 0° C. The reaction mixture was filtered through a plug of Celite™ (diatomaceous earth) and the filtrate was washed with ethyl acetate (30 mL). The combined organic fractions were evaporated under reduced pressure. The residue was purified by reverse phase HPLC to afford the indicated product. Chiral separation using SFC on a Chiralcel OJ column provided both enantiomers of the title compound. 1H NMR (500 MHz, CD3COCD3): δ 0.58 (m, 2H); 0.73 (M, 2H); 1.78 (s, 3H); 2.68 (s, 3H), 2.80 (m, 1H); 3.10 (m, 2H); 4.94 (t, J=7.1 Hz, 2H); 7.26 (d, J=8.2 Hz, 2H); 7.52 (br, 1H); 7.79 (br, 1H); 8.74 (d, J=8.2 Hz, 1H). m/z=525.17 (M+H).

Workup

  1. filtrationThe reaction mixture was filtered through a plug of Celite™ (diatomaceous earth)
  2. washthe filtrate was washed with ethyl acetate (30 mL)
  3. customThe combined organic fractions were evaporated under reduced pressure
  4. customThe residue was purified by reverse phase HPLC
  5. customto afford the indicated product
  6. customChiral separation

Sources & evidence

ORD record
ord-f97774f89a744534a6237a4fe927c3e0
Source dataset
uspto-grants-2016_06
Patent number
US09365574B2

Reaction notes

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