Dimethyl Sulfoxide → HCID 46869451, compound

HRID 578662Notes

Reaction equation

HRID 578662 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]([NH:10][C:11]2[CH:12]=[C:13]([CH:17]([NH:22][C:23]3[C:32]4[C:27](=[C:28]([C:33]([NH2:35])=[O:34])[CH:29]=[CH:30][CH:31]=4)[N:26]=[CH:25][N:24]=3)[CH2:18][N:19]([CH3:21])[CH3:20])[CH:14]=[CH:15][CH:16]=2)=[O:9])[CH:5]=[CH:4][N:3]=1.CC(O)(C)C.CS(C)=O.[NH:45]1[CH2:49][CH2:48][CH2:47][CH2:46]1>O>[CH3:20][N:19]([CH3:21])[CH2:18][CH:17]([NH:22][C:23]1[C:32]2[C:27](=[C:28]([C:33]([NH2:35])=[O:34])[CH:29]=[CH:30][CH:31]=2)[N:26]=[CH:25][N:24]=1)[C:13]1[CH:14]=[CH:15][CH:16]=[C:11]([NH:10][C:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([N:45]3[CH2:49][CH2:48][CH2:47][CH2:46]3)[CH:7]=2)=[O:9])[CH:12]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 6386tert-ButanolHCID 31268Pyrrolidine2×HCID 46869518HCID 46869518, compound

Product 1

HCID 46869451HCID 46869451, compoundYield 36%

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-(1-{3-[(2-Chloro-pyridine-4-carbonyl)-amino]-phenyl}-2-dimethylamino-ethylamino)-quinazoline-8-carboxylic acid amide (0.045 g, 0.092 mmol, 1 eq.), t-BuOH (2 mL), DMSO (1 mL), and Pyrrolidine (0.076 mL, 0.92 mmol, 10 eq.). The vial was capped and heated under microwave conditions (50 W, 20 min. ramp, 110° C., STND, 1 hr. hold time) followed by addition of another aliquot of Pyrrolidine (0.1 mL) then microwaved (70 W, 20 min. ramp, 140° C., STND, 1 hr. hold time). Reaction was diluted with water (20 mL) and extracted with EtOAc (3×30 mL). The combined organics were washed with brine, dried (e.g., Na2SO4), filtered and concentrated. The resulting residue was purified via preparative HPLC afforded the desired compound as a white solid (17.3 mg, 36% yield) LCMS (ESI) 525 (M+H).

Workup

  1. customThe vial was capped
  2. customthen microwaved (70 W, 20 min. ramp, 140° C., STND, 1 hr. hold time)
  3. customReaction
  4. extractionextracted with EtOAc (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 via preparative HPLC

Sources & evidence

ORD record
ord-d2849402a782448386e7a65b7ad3a4f6
Source dataset
uspto-grants-2015_05
Patent number
US09040560B2

Reaction notes

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