Trifluoroacetic acid → HCID 117842692, compound

HRID 2209229Notes

Reaction equation

HRID 2209229 reaction equation
[C:1](O)([C:3](F)(F)F)=[O:2].[O:8]=[C:9]1[NH:13][CH2:12][C@H:11]([C@H:14]([O:16][C:17]2[C:18]3[N:19]([N:35]=[CH:36][C:37]=3[C:38]#[N:39])[CH:20]=[C:21]([C:23]3[CH:28]=[CH:27][C:26]([N:29]4[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]4)=[CH:25][CH:24]=3)[N:22]=2)[CH3:15])[CH2:10]1.CCN(CC)CC.C(OC(=O)C)(=O)C>C(Cl)Cl>[C:1]([N:32]1[CH2:31][CH2:30][N:29]([C:26]2[CH:25]=[CH:24][C:23]([C:21]3[N:22]=[C:17]([O:16][C@@H:14]([C@@H:11]4[CH2:10][C:9](=[O:8])[NH:13][CH2:12]4)[CH3:15])[C:18]4[N:19]([N:35]=[CH:36][C:37]=4[C:38]#[N:39])[CH:20]=3)=[CH:28][CH:27]=2)[CH2:34][CH2:33]1)(=[O:2])[CH3:3]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 117843400HCID 117843400, compound

Product 1

HCID 117842692HCID 117842692, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The crude TFA salt of 5.67 (0.107 mmol) was dissolved in DCM (2 mL) and was treated with Et3N (0.15 mL, 1.1 mmol) followed by acetic anhydride (13 μL, 0.13 mmol). After stirring for 1.5 h, the reaction mixture was partitioned between DCM and water, and the aqueous phase was extracted with DCM. The combined organic phase was dried over Na2SO4, filtered, and concentrated, and the concentrate was purified by silica gel (0-15% MeOH in DCM) to afford 6-(4-(4-acetylpiperazin-1-yl)phenyl)-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)pyrazolo[1,5-a]pyrazine-3-carbonitrile (5.68). LCMS-ESI+ (m/z): [M+H]+ calcd for C25H28N7O3: 474.2; found: 474.3. 1H NMR (400 MHz, Chloroform-d) δ 8.41 (s, 1H), 8.18 (s, 1H), 7.86-7.78 (m, 2H), 7.04-6.96 (m, 2H), 6.10 (s, 1H), 5.65-5.52 (m, 1H), 3.85-3.73 (m, 2H), 3.66 (dd, J=6.4, 4.0 Hz, 2H), 3.63-3.55 (m, 1H), 3.44 (dd, J=9.9, 6.7 Hz, 1H), 3.34-3.23 (m, 4H), 3.12-2.96 (m, 1H), 2.60 (dd, J=17.1, 9.2 Hz, 1H), 2.43 (dd, J=17.1, 8.0 Hz, 1H), 2.15 (s, 3H), 1.54 (d, J=6.2 Hz, 3H).

Workup

  1. customthe reaction mixture was partitioned between DCM and water
  2. extractionthe aqueous phase was extracted with DCM
  3. dry with materialThe combined organic phase was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customthe concentrate was purified by silica gel (0-15% MeOH in DCM)

Sources & evidence

ORD record
ord-61899c87254c40bbb672d3961decd016
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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