Tetrahydrofuran → [1-(2,4-difluoro-phenyl)-3-(5-methyl-1H-pyrazol-3-ylamino)-isoquinolin-6-yl]-morpholin-4-yl-methanone

HRID 2101046Notes

Reaction equation

HRID 2101046 reaction equation
FC(F)(F)S(O[C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[C:13]([C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=1[F:24])=[N:12][C:11]([NH:25][C:26]1[CH:30]=[C:29]([CH3:31])[NH:28][N:27]=1)=[CH:10]2)(=O)=O.[NH:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1.N12CCCNC1CCCC=C2.[O:51]1CCC[CH2:52]1>CC([O-])=O.CC([O-])=O.[Pd+2]>[F:24][C:18]1[CH:19]=[C:20]([F:23])[CH:21]=[CH:22][C:17]=1[C:13]1[C:14]2[C:9](=[CH:8][C:7]([C:52]([N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)=[O:51])=[CH:16][CH:15]=2)[CH:10]=[C:11]([NH:25][C:26]2[CH:30]=[C:29]([CH3:31])[NH:28][N:27]=2)[N:12]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8083MorpholineHCID 98128211,8-Diazabicyclo[5.4.0]undec-2-eneHCID 57799527HCID 57799527, compound

Product 1

HCID 57799771[1-(2,4-difluoro-phenyl)-3-(5-methyl-1H-pyrazol-3-ylamino)-isoquinolin-6-yl]-morpholin-4-yl-methanone

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
150 °C

Procedure

A 0.5-2.0 mL process vial was charged with 1-(2,4-difluoro-phenyl)-3-(5-methyl-1H-pyrazol-3-ylamino)-isoquinolin-6-yl trifluoromethanesulfonate (24.3 mg), Pd(OAc)2 (2 mg), Mo(CO)6 (13.2 mg), morpholine (13.0 mg), 1,8-Diazabicyclo[5.4.0]undecen (DBU) (22.9 mg), and dry tetrahydrofuran (THF) (1 mL). The vial was immediately capped under air and heated at 150° C. for 15 min under microwave irradiation. After cooling, the reaction mixture was filtered through a short silica gel column, and the solvent was removed under reduced pressure. The residue was sent to prep-HPLC to get 5 mg of [1-(2,4-difluoro-phenyl)-3-(5-methyl-1H-pyrazol-3-ylamino)-isoquinolin-6-yl]-morpholin-4-yl-methanone as a yellow solid. LC-MS m/e 450 MH+. 1H NMR (400 MHz, CDCl3) 7.74(s, 1H), 7.70(s, 1H), 7.66(m, 1H), 7.54(m, 1H), 7.24(m, 1H), 7.10(t, 1H), 7.02(t, 1H), 6.00(s, 1H), 3.83˜3.48(m, 8H), 2.33(s, 3H).

Workup

  1. customThe vial was immediately capped under air
  2. temperatureAfter cooling
  3. filtrationthe reaction mixture was filtered through a short silica gel column
  4. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-315c4710c927491a871feff6f162c0f8
Source dataset
uspto-grants-2009_08
Patent number
US07572809B2

Reaction notes

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