Diisopropylethylamine → HCID 178451904, compound

HRID 1625526Notes

Reaction equation

HRID 1625526 reaction equation
[I:1][C:2]1[CH:3]=[C:4]([NH2:9])[C:5]([NH2:8])=[CH:6][CH:7]=1.[C:10]([O:14][C:15]([N:17]1[CH2:21][CH2:20][CH2:19][C@H:18]1[C:22](O)=O)=[O:16])([CH3:13])([CH3:12])[CH3:11].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(OCC)(=O)C.O.C1COCC1>[C:10]([O:14][C:15]([N:17]1[CH2:21][CH2:20][CH2:19][C@H:18]1[C:22]1[NH:8][C:5]2[CH:6]=[CH:7][C:2]([I:1])=[CH:3][C:4]=2[N:9]=1)=[O:16])([CH3:13])([CH3:11])[CH3:12]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 112070494-Iodobenzene-1,2-diamine

Product 1

HCID 178451904HCID 178451904, compoundYield 84.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
1 °C

Procedure

To a dry 1000 mL round bottom flask under Nitrogen, is added 4-iodo-benzene-1,2-diamine (45 g), (S)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (41.39 g) and THF (450 ml). The reaction mixture is stirred until complete dissolution then cooled to 0-2° C. DIPEA (50.17 ml) is added dropwise to control the exotherm then HATU (80.38 g) is added in one portion. The reaction mixture is stirred in an ice bath for 3 hours and followed by HPLC to monitor completion of reaction. To this solution are added 500 ml of water and 500 ml of ethyl acetate. The aqueous phase is extracted twice with ethyl acetate. The organic phases are combined and evaporated half. To the organic phase is added 450 ml of acetic acid and the mixture is evaporated to 300 ml. This procedure is repeated 3 times for a residual of −470 ml, and the mixture is then heated at 50° C. over night. Toluene (200 ml) is added and evaporated to a small residue (repeated 6 times). To this solution is added 450 ml of ethyl acetate. The organic phase is washed with saturated sodium carbonate, dried over sodium sulfate, filtered and evaporated to dryness. The residue is purified on a pad of silica using 25% ethyl acetate/hexane mixture to give (S)-2-(5-Iodo-1H-benzoimidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (67 g) as a beige powder.

Workup

  1. stirringThe reaction mixture is stirred in an ice bath for 3 hours
  2. customcompletion of reaction
  3. extractionThe aqueous phase is extracted twice with ethyl acetate
  4. customevaporated half
  5. additionTo the organic phase is added 450 ml of acetic acid
  6. customthe mixture is evaporated to 300 ml
  7. temperaturethe mixture is then heated at 50° C. over night
  8. additionToluene (200 ml) is added
  9. customevaporated to a small residue (repeated 6 times)
  10. additionTo this solution is added 450 ml of ethyl acetate
  11. washThe organic phase is washed with saturated sodium carbonate
  12. dry with materialdried over sodium sulfate
  13. filtrationfiltered
  14. customevaporated to dryness
  15. customThe residue is purified on a pad of silica using 25% ethyl acetate/hexane mixture

Sources & evidence

ORD record
ord-ce8c364544e44b79ac7d8604ab3c1b07
Source dataset
uspto-grants-2014_07
Patent number
US08779156B2

Reaction notes

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