1,1'-Carbonyldiimidazole → Diisopropyl Ether

HRID 400396Notes

Reaction equation

HRID 400396 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([S:8]([C:11]2[CH:12]=[C:13]([CH:16]=[CH:17][C:18]=2[O:19][C:20]2[CH:25]=[C:24]([Cl:26])[CH:23]=[C:22]([Cl:27])[CH:21]=2)[C:14]#[N:15])(=[O:10])=[O:9])[CH2:4][CH2:3]1.[C:28]([N:35]1[CH:39]=[CH:38][N:37]=[CH:36]1)(N1C=CN=C1)=[O:29].NCCN1C[CH2:47][O:46][CH2:45][CH2:44]1>C1COCC1.ClCCl>[C:14]([C:13]1[CH:16]=[CH:17][C:18]([O:19][C:20]2[CH:21]=[C:22]([Cl:27])[CH:23]=[C:24]([Cl:26])[CH:25]=2)=[C:11]([S:8]([N:5]2[CH2:4][CH2:3][CH:2]([NH:1][C:28]([NH:35][CH2:39][CH2:38][N:37]3[CH2:36][CH2:47][O:46][CH2:45][CH2:44]3)=[O:29])[CH2:7][CH2:6]2)(=[O:10])=[O:9])[CH:12]=1)#[N:15].[CH:18]([O:19][CH:20]([CH3:25])[CH3:21])([CH3:17])[CH3:11]

Participants

7

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 4082852-MorpholinoethylamineHCID 58442575HCID 58442575, compound

Product 2

HCID 7914Diisopropyl EtherHCID 53373580HCID 53373580, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

1-(1-(5-cyano-2-(3,5-dichlorophenoxy)phenylsulfonyl)-piperidin-4-yl)-3-(2-morpholinoethyl)urea (22) is prepared according to the following method as an alternative to the method of Example 32. 3-(4-aminopiperidin-1-ylsulfonyl)-4-(3,5-dichlorophenoxy)-benzonitrile (1.002 g), prepared according to Example 1, and carbonyldiimidazole (420 mg, 1.1 eq.) were combined in THF (15 mL) and stirred at room temperature. After 5 hours, starting material was consumed (confirmed by HPLC). 4-(2-aminoethyl)morpholine (512 mg, 2.0 eq.) was added and the mixture was stirred 19 hours. Concentration in vacuo provided a white solid, which was resuspended in dichlormethane, partitioned with water, and the aqueous layer extracted three times with dichloromethane. The combined organic layers were washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to yield a white solid. Trituration with isopropyl ether yielded a 96% pure product according to HPLC. The powder was suspended in minimal amounts of hot methanol, stirred at 60° C. for 30 minutes, cooled in an ice bath and vacuum filtered to obtain the product as a white powder (831 mg, 60.7% yield, 98% purity).

Workup

  1. customwas consumed (confirmed by HPLC)
  2. stirringthe mixture was stirred 19 hours
  3. concentrationConcentration in vacuo
  4. customprovided a white solid, which
  5. custompartitioned with water
  6. extractionthe aqueous layer extracted three times with dichloromethane
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto yield a white solid

Sources & evidence

ORD record
ord-fdc6908d19524ed9b2665ac855ac0b3c
Source dataset
uspto-grants-2014_06
Patent number
US08741894B2

Reaction notes

Loading…