Acetic Anhydride → 3-(1-acetylpiperidin-4-yl)-3-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)propanenitrile

HRID 1852982Notes

Reaction equation

HRID 1852982 reaction equation
Cl.[CH3:2][N:3]1[CH:7]=[C:6]([C:8]2[N:13]=[C:12]([C:14]3[CH:15]=[N:16][N:17]([CH:19]([CH:23]4[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]4)[CH2:20][C:21]#[N:22])[CH:18]=3)[N:11]3[CH:29]=[CH:30][N:31]=[C:10]3[CH:9]=2)[CH:5]=[N:4]1.C1C[O:35][CH2:34][CH2:33]1.C(N(CC)CC)C.C(OC(=O)C)(=O)C>C(=O)(O)[O-].[Na+].CCOC(C)=O>[C:34]([N:26]1[CH2:27][CH2:28][CH:23]([CH:19]([N:17]2[CH:18]=[C:14]([C:12]3[N:11]4[CH:29]=[CH:30][N:31]=[C:10]4[CH:9]=[C:8]([C:6]4[CH:5]=[N:4][N:3]([CH3:2])[CH:7]=4)[N:13]=3)[CH:15]=[N:16]2)[CH2:20][C:21]#[N:22])[CH2:24][CH2:25]1)(=[O:35])[CH3:33]

Participants

7

Reactant 4

HCID 7918Acetic AnhydrideHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 866853073-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)-3-(piperidin-4-yl)propanenitrile hydrochloride

Product 1

HCID 682307493-(1-acetylpiperidin-4-yl)-3-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)propanenitrileYield 77.3%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

3-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)-3-(piperidin-4-yl)propanenitrile hydrochloride (10.0 mg, 0.021 mmol) was suspended in THF (211 μL, 0.0211 mmol). To this was added triethylamine (8.81 DIPHOS, 0.0632 mmol) to free-base. Acetic anhydride (2.38 μL, 0.0253 mmol) was added and the reaction mixture stirred at ambient temperature for 30 minutes. The reaction mixture was then diluted in saturated sodium bicarbonate and EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried with MgSO4, filtered and concentrated in vacuo. Purification of the resulting crude material by reverse phase HPLC using 0-100% acetonitrile/water gradient afforded the title compound (7.2 mg, 77% yield). MS (apci) m/z=444.3 (M+H).

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with EtOAc
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried with MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification of the resulting crude material by reverse phase

Sources & evidence

ORD record
ord-a0dcd2ed781343f2a08236443c88c884
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

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