Dimethyl Sulfoxide → HCID 66763951, compound

HRID 578670Notes

Reaction equation

HRID 578670 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]([NH:10][C:11]2[CH:12]=[C:13]([CH:29]=[CH:30][CH:31]=2)[CH2:14][NH:15][C:16]2[C:25]3[C:20](=[C:21]([C:26]([NH2:28])=[O:27])[CH:22]=[CH:23][CH:24]=3)[N:19]=[CH:18][N:17]=2)=[O:9])[CH:5]=[CH:4][N:3]=1.CC(O)(C)C.CS(C)=O.[NH:41]1[CH2:45][CH2:44][CH2:43][CH2:42]1>O>[N:41]1([C:2]2[CH:7]=[C:6]([C:8]([NH:10][C:11]3[CH:12]=[C:13]([CH:29]=[CH:30][CH:31]=3)[CH2:14][NH:15][C:16]3[C:25]4[C:20](=[C:21]([C:26]([NH2:28])=[O:27])[CH:22]=[CH:23][CH:24]=4)[N:19]=[CH:18][N:17]=3)=[O:9])[CH:5]=[CH:4][N:3]=2)[CH2:45][CH2:44][CH2:43][CH2:42]1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 6386tert-ButanolHCID 31268Pyrrolidine2×HCID 86662385HCID 86662385, compound

Product 1

HCID 66763951HCID 66763951, compoundYield 49%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

To a 10-mL microwave-rated vial with magnetic stir bar at r.t. was added 4-{3-[(2-Chloro-pyridine-4-carbonyl)-amino]-benzylamino}-quinazoline-8-carboxylic acid amide (0.05 g, 0.115 mmol, 1 eq.), t-BuOH (2 mL), DMSO (1 mL), and pyrrolidine (0.1 mL, 1.15 mmol, 10 eq.). The vial was capped and heated under microwave conditions (50 W, 3 min. ramp, 110° C., STND, 1 hr. hold time) followed by addition of another aliquot of pyrrolidine (0.1 mL) then microwaved (70 W, 3 min. ramp, 140° C., STND, 1 hr. hold time). Reaction was diluted with water (20 mL) and extracted with DCM (3×30 mL). The combined organics were washed with brine, dried (e.g., Na2SO4), filtered and concentrated. The resulting residue was purified by column chromatography (ISCO CombiFlash) using a 0-30% gradient (10% MeOH in EtOAc/EtOAc) afforded 25 mg (49% yield). LCMS (ESI) 468 (M+H).

Workup

  1. customThe vial was capped
  2. customthen microwaved (70 W, 3 min. ramp, 140° C., STND, 1 hr. hold time)
  3. customReaction
  4. extractionextracted with DCM (3×30 mL)
  5. washThe combined organics were washed with brine
  6. dry with materialdried (e.g., Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resulting residue was purified by column chromatography (ISCO CombiFlash)
  10. customafforded 25 mg (49% yield)

Sources & evidence

ORD record
ord-73df44c3f6f74c9ba69fa9fdb86a8d53
Source dataset
uspto-grants-2015_05
Patent number
US09040560B2

Reaction notes

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