2-Aminopropanol → HCID 10392564, compound

HRID 1371693Notes

Reaction equation

HRID 1371693 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([C:10]2[C:15]([O:16][CH3:17])=[CH:14][CH:13]=[C:12]([F:18])[C:11]=2[F:19])=[O:9])=[CH:6][N:5]=[C:4]([NH:20][CH:21]2[CH2:26][CH2:25][N:24]([S:27]([CH2:30][CH2:31][CH2:32]Cl)(=[O:29])=[O:28])[CH2:23][CH2:22]2)[N:3]=1.[CH3:34][CH:35]([NH2:38])[CH2:36][OH:37].[I-].[Na+]>O1CCCC1>[NH2:1][C:2]1[C:7]([C:8]([C:10]2[C:15]([O:16][CH3:17])=[CH:14][CH:13]=[C:12]([F:18])[C:11]=2[F:19])=[O:9])=[CH:6][N:5]=[C:4]([NH:20][CH:21]2[CH2:26][CH2:25][N:24]([S:27]([CH2:30][CH2:31][CH2:32][NH:38][CH:35]([CH3:34])[CH2:36][OH:37])(=[O:29])=[O:28])[CH2:23][CH2:22]2)[N:3]=1

Participants

5

Reactant 3

HCID 51262-AminopropanolHCID 5238Sodium IodideHCID 9983584[4-Amino-2-[1-(3-chloro-propane-1-sulfonyl)-piperidin-4-ylamino]-pyrimidin-5-yl]-(2,3-difluoro-6-methoxy-phenyl)-methanone

Product 1

HCID 10392564HCID 10392564, compoundYield 65.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
150 °C

Procedure

The reaction mixture of [4-amino-2-[1-(3-chloro-propane-1-sulfonyl)-piperidin-4-ylamino]-pyrimidin-5-yl]-(2,3-difluoro-6-methoxy-phenyl)-methanone (100 mg, 0.198 mmol, Example 226), dl-2-amino-1-propanol (158 uL, 1.980 mmol, TCI) and sodium iodide (30 mg, 0.198 mmol) in tetrahydrofuran (4 mL) was heated at 150° C. for 1 hour using a Smith Creator microwave synthesizer. Upon cooling to room temperature, the solvent was removed and acetonitrile (3 mL) was added. The mixture was filtered and trifluoroacetic acid (0.25 mL) was added. Purification by reverse phase HPLC (C18, eluting with acetonitrile and water) gave (4-amino-2-[1-[3-(2-hydroxy-1-methyl-ethylamino)-propane-1-sulfonyl]-piperidin-4-ylamino]-pyrimidin-5-yl)-(2,3-difluoro-6-methoxy-phenyl)-methanone (70 mg, 65% yield) as off-white solids. HR-MS (ES, m/z) calculated for C23H33N6O5SF2 [(M+H)+] 543.2196, observed 543.2202.

Workup

  1. temperatureUpon cooling to room temperature
  2. customthe solvent was removed
  3. additionacetonitrile (3 mL) was added
  4. filtrationThe mixture was filtered
  5. additiontrifluoroacetic acid (0.25 mL) was added
  6. customPurification
  7. washby reverse phase HPLC (C18, eluting with acetonitrile and water)

Sources & evidence

ORD record
ord-547518253c0a4b658a4c8da26914d485
Source dataset
uspto-grants-2007_01
Patent number
US07157455B2

Reaction notes

Loading…