Acetonitrile → HCID 66712146, compound

HRID 1262265Notes

Reaction equation

HRID 1262265 reaction equation
[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]3[N:19]=[CH:18][C:17]4=[CH:20][CH:21]=[C:22]([C:23]5[CH2:24][CH2:25][NH:26][CH2:27][CH:28]=5)[N:16]4[N:15]=3)=[CH:9][CH:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C(#N)C.C(=O)([O-])[O-].[K+].[K+].[CH3:38][S:39](Cl)(=[O:41])=[O:40]>>[CH3:38][S:39]([N:26]1[CH2:25][CH:24]=[C:23]([C:22]2[N:16]3[C:17]([CH:18]=[N:19][C:14]([NH:13][C:10]4[CH:11]=[CH:12][C:7]([N:1]5[CH2:2][CH2:3][O:4][CH2:5][CH2:6]5)=[CH:8][CH:9]=4)=[N:15]3)=[CH:20][CH:21]=2)[CH2:28][CH2:27]1)(=[O:41])=[O:40]

Participants

5

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 66712194HCID 66712194, compound

Product 1

HCID 66712146HCID 66712146, compoundYield 36.7%

Procedure

Into a 8-dram vial, (4-Morpholin-4-yl-phenyl)-[7-(1,2,3,6-tetrahydro-pyridin-4-yl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-amine (0.080 g, 0.21 mmol), Acetonitrile (15 mL, 290 mmol), Potassium carbonate (0.0587 g, 0.425 mmol) were added and stirred for 5 minutes. Methanesulfonyl chloride (0.0256 g, 0.223 mmol) was added. The reaction was stirred at room temperature over night. The solvent was removed under vacuum. The reaction was partitioned with water and DCM. The organic was separated, washed with Brine and dried over Na2SO4. The solid was filtered and washed with DCM. The solvent was removed under vacuum. The reaction mixture was purified via ISCO column chromatography with DCM and methanol as eluant (0 to 10% methanol). The collected fractions afforded [7-(1-Methanesulfonyl-1,2,3,6-tetrahydro-pyridin-4-yl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-morpholin-4-yl-phenyl)-amine as a yellow solid (35 mg, 36%). LCMS (E/I+) 455.10 (M+H). MP 238-240° C. NMR 1H (DMSO-d6)-9.18 (s, 1H), 8.90 (s, 1H), 7.56 (d, 2H, J=8.88 Hz), 7.19 (bs, 1H), 6.94 (d, 2H, J=8.88 Hz), 6.83 (d, 1H, J=4.72 Hz), 6.81 (d, 1H, J=4.72 Hz), 4.00 (bs, 2H), 3.75 (t, 4H, J=5.26 Hz), 3.42 (t, 2H, J=5.96 Hz), 3.05 (t, 4H, J=5.26 Hz), 2.97 (s, 3H), 2.72 (bs, 2H).

Workup

  1. stirringThe reaction was stirred at room temperature over night
  2. customThe solvent was removed under vacuum
  3. customThe reaction was partitioned with water and DCM
  4. customThe organic was separated
  5. washwashed with Brine
  6. dry with materialdried over Na2SO4
  7. filtrationThe solid was filtered
  8. washwashed with DCM
  9. customThe solvent was removed under vacuum
  10. customThe reaction mixture was purified via ISCO column chromatography with DCM and methanol as eluant (0 to 10% methanol)

Sources & evidence

ORD record
ord-1f408c7f64bf4df08eecba4736eb7bfa
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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