Dimethylformamide → HCID 86687958, compound

HRID 2370782Notes

Reaction equation

HRID 2370782 reaction equation
ClC1[CH:31]=[CH:30][C:5]([C:6]([NH:8][C@@H:9]([C:20]2[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=2)[C:10]2[C:15]([C:16]([F:19])([F:18])[F:17])=[CH:14][CH:13]=[CH:12][N:11]=2)=[O:7])=[CH:4][N:3]=1.C(NCC)C.C1COCC1.[CH3:42][N:43]([CH:45]=O)[CH3:44]>>[CH3:44][N:43]([CH3:42])[C:45]1[CH:31]=[CH:30][C:5]([C:6]([NH:8][C@@H:9]([C:20]2[CH:21]=[CH:22][C:23]([C:26]([F:29])([F:27])[F:28])=[CH:24][CH:25]=2)[C:10]2[C:15]([C:16]([F:17])([F:18])[F:19])=[CH:14][CH:13]=[CH:12][N:11]=2)=[O:7])=[CH:4][N:3]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 8021DiethylamineHCID 8028TetrahydrofuranHCID 86687959HCID 86687959, compound

Product 1

HCID 86687958HCID 86687958, compound

Conditions

Temperature
100 °C

Procedure

A glass microwave reaction vessel was charged with (S)-6-chloro-N-((4-(trifluoromethyl)phenyl)(3-(trifluoromethyl)pyridin-2-yl)methyl)nicotinamide (50 mg, 0.109 mmol, example 135), DMF (1 mL), and 2 M diethylamine in THF (0.054 mL, 0.109 mmol). The reaction mixture was stirred and heated in a Biotage Initiator at 100° C. for 30 minutes. This was repeated at 150° C. for 30 minutes at a time until LC-MS indicated complete consumption of starting material. The reaction product was purified by reverse-phase preparative HPLC (Shimadzu) on a Phenomenex Gemini column (5 micron, C18, 110 Å, Axia, 100×30 mm) eluting at 45 mL/min with a linear gradient of 20% to 70% MeCN (0.1% TFA) in water (0.1% TFA) over 20 minutes. The desired fractions were poured into 10% Na2CO3 and extracted with DCM (3×5 mL). The combined DCM layers were washed with brine, dried over MgSO4, and concentrated in vacuo to give the title compound as a white solid. 1H NMR (CDCl3, 300 MHz) δ ppm 8.86 (d, J=3.8 Hz, 1H), 8.66 (d, J=2.2 Hz, 1H), 8.02 (d, J=7.9 Hz, 2H), 7.92 (dd, J=9.1, 2.5 Hz, 1H), 7.54 (s, 4H), 7.45 (dd, J=7.7, 4.4 Hz, 1H), 6.87 (d, J=7.9 Hz, 1H), 6.49 (d, J=9.2 Hz, 1H), 3.14 (s, 6H) MS (ESI pos. ion) m/z: 469.0 (M+H).

Workup

  1. customA glass microwave reaction vessel
  2. customconsumption of starting material
  3. customThe reaction product was purified by reverse-phase preparative HPLC (Shimadzu) on a Phenomenex Gemini column (5 micron, C18, 110 Å, Axia, 100×30 mm)
  4. washeluting at 45 mL/min with a linear gradient of 20% to 70% MeCN (0.1% TFA) in water (0.1% TFA) over 20 minutes
  5. additionThe desired fractions were poured into 10% Na2CO3
  6. extractionextracted with DCM (3×5 mL)
  7. washThe combined DCM layers were washed with brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ebb5c6fa5c95438e9225733e4e1de6e6
Source dataset
uspto-grants-2014_04
Patent number
US08710043B2

Reaction notes

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