Dichloromethane → HCID 71608033, compound

HRID 1188263Notes

Reaction equation

HRID 1188263 reaction equation
[CH3:1][S:2]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[C:21](=[O:22])[C:20]3[C:15](=[CH:16][C:17]([C:23]#[C:24][CH:25]4[CH2:28][N:27]([C:29]([O:31]C(C)(C)C)=O)[CH2:26]4)=[CH:18][CH:19]=3)[O:14][CH:13]=2)=[CH:8][CH:7]=1)(=[O:4])=[O:3].F[C:37](F)(F)[C:38](O)=O.Cl[CH2:44]Cl>>[CH:38]1([C:29]([N:27]2[CH2:26][CH:25]([C:24]#[C:23][C:17]3[CH:16]=[C:15]4[C:20]([C:21](=[O:22])[C:12]([C:9]5[CH:8]=[CH:7][C:6]([NH:5][S:2]([CH3:1])(=[O:3])=[O:4])=[CH:11][CH:10]=5)=[CH:13][O:14]4)=[CH:19][CH:18]=3)[CH2:28]2)=[O:31])[CH2:37][CH2:44]1

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 71504444HCID 71504444, compound

Product 1

HCID 71608033HCID 71608033, compound

Procedure

To a solution of tert-butyl 3-((3-(4-(methylsulfonamido)phenyl)-4-oxo-4H-chromen-7-yl)ethynyl)azetidine-1-carboxylate (103 mgs, 0.209 mmol) in dichloromethane (2 mL), trifluoroacetic acid (0.2 mL, 2.08 mmol) was added and stirred at room temperature. After 2 hours the reaction mixture was concentrated and the residue dried under reduced pressure. The crude material was dissolved in dichloromethane (3 mL) and diisopropylethylamine (0.2 mL) and cyclopropanecarbonyl chloride (0.1 mL) were added, and the mixture stirred at room temperature. After 16 hours, the reaction mixture was concentrated under reduced pressure, and the residue dissolved in tetrahydrofuran (2 mL) and 7N ammonia in methanol (4 mL) was added, and the mixture was stirred for 14 hours. The reaction mixture was then concentrated and chromatographed (SiO2, 5% methanol/ethyl acetate) to provide N-(4-(7-((1-(cyclopropanecarbonyl)azetidin-3-yl)ethynyl)-4-oxo-4H-chromen-3-yl)phenyl)methanesulfonamide:

Workup

  1. concentrationAfter 2 hours the reaction mixture was concentrated
  2. customthe residue dried under reduced pressure
  3. dissolutionThe crude material was dissolved in dichloromethane (3 mL)
  4. additiondiisopropylethylamine (0.2 mL) and cyclopropanecarbonyl chloride (0.1 mL) were added
  5. stirringthe mixture stirred at room temperature
  6. concentrationthe reaction mixture was concentrated under reduced pressure
  7. dissolutionthe residue dissolved in tetrahydrofuran (2 mL)
  8. addition7N ammonia in methanol (4 mL) was added
  9. stirringthe mixture was stirred for 14 hours
  10. concentrationThe reaction mixture was then concentrated
  11. customchromatographed (SiO2, 5% methanol/ethyl acetate)

Sources & evidence

ORD record
ord-864222688f20452bbadb45c9b251f23b
Source dataset
uspto-grants-2014_03
Patent number
US08673966B2

Reaction notes

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