Triphosgene → HCID 21906648, compound

HRID 988655Notes

Reaction equation

HRID 988655 reaction equation
[NH2:1][CH:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1.[C:14]([O:18]C(N1CCC(O)C1)=O)(C)(C)C.ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.[NH2:39][C:40]1[CH:55]=[CH:54][CH:53]=[CH:52][C:41]=1[C:42]([NH:44][C:45]1[CH:50]=[CH:49][C:48]([Cl:51])=[CH:47][N:46]=1)=[O:43].[N-]=C=O>C(Cl)Cl.C(N(CC)CC)C>[C:10]([O:9][C:7]([N:4]1[CH2:5][CH2:6][CH:2]([NH:1][C:14]([NH:39][C:40]2[CH:55]=[CH:54][CH:53]=[CH:52][C:41]=2[C:42]([NH:44][C:45]2[CH:50]=[CH:49][C:48]([Cl:51])=[CH:47][N:46]=2)=[O:43])=[O:18])[CH2:3]1)=[O:8])([CH3:13])([CH3:12])[CH3:11]

Participants

8

Reactant 5

HCID 94429TriphosgeneHCID 105034IsocyanateHCID 27563701-Boc-3-aminopyrrolidineHCID 44169391-Boc-3-pyrrolidinolHCID 219063812-amino-N-(5-chloropyridin-2-yl)benzamide

Product 1

HCID 21906648HCID 21906648, compoundYield 35%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 8471TriethylamineSolvent2×

Procedure

A solution of 3-amino-1-tert-butoxycarbonylpyrrolidine (200 mg, 1.08 mmol; prepared from 1-tert-butoxycarbonyl-3-hydroxy-pyrrolidine using a similar procedure to that described in Example 77-B) and triethylamine (0.38 mL) in methylene chloride (3.5 mL) was added dropwise to a solution of triphosgene (120 mg, 0.403 mmol) in methylene chloride (2 mL). After complete addition, a solution of 2-amino-N-(5-chloropyridin-2-yl)benzamide (242 mg, 0.983 mmol) and triethylamine (0.38 mL) in methylene chloride (3.5 mL) was added in one portion. After 16 h, the mixture was treated with an additional equivalent of the isocyanate. After 1 h, the mixture was concentrated and the residue was partitioned between EtOAc and water. The organic layer was washed with 0.5 N HCl (2×), satd sodium bicarbonate (1×), water, brine, dried with sodium sulfate, and concentrated. The residue was purified by column chromatography (SiO2: 40 to 50% EtOAc in hexanes) affording 160 mg (35%) of the title compound.

Workup

  1. additionAfter complete addition
  2. waitAfter 1 h
  3. concentrationthe mixture was concentrated
  4. customthe residue was partitioned between EtOAc and water
  5. washThe organic layer was washed with 0.5 N HCl (2×), satd sodium bicarbonate (1×), water, brine
  6. dry with materialdried with sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography (SiO2: 40 to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-cfefb81f798f4eb797fca834f9b3c503
Source dataset
uspto-grants-2003_10
Patent number
US06635657B1

Reaction notes

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