Triethylamine → HCID 51352798, compound

HRID 77403Notes

Reaction equation

HRID 77403 reaction equation
[N:1]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[N:4]([C:10]1[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=1)[N:16]=[C:15]([C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[CH:21]=1)[N:14]([CH2:27][C:28](O)=[O:29])[C:13]3=[O:31])[CH2:3][CH2:2]2.Cl.[CH3:33][NH:34][CH3:35].C(N(CC)CC)C.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O.C(OCC)(=O)C>ClCCl>[N:1]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[N:4]([C:10]1[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=1)[N:16]=[C:15]([C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[CH:21]=1)[N:14]([CH2:27][C:28]([N:34]([CH3:35])[CH3:33])=[O:29])[C:13]3=[O:31])[CH2:3][CH2:2]2

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 10473Dimethylamine, hydrochlorideHCID 111923Propylphosphonic anhydrideHCID 699285372-(6-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-2-(3-chlorophenyl)-4-oxoquinazolin-3(4H)-yl)acetic acid2×

Product 1

HCID 51352798HCID 51352798, compoundYield 10.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-(6-(1,4-Diazabicyclo[3.2.2]nonan-4-yl)-2-(3-chlorophenyl)-4-oxoquinazolin-3(4H)-yl)acetic acid (Intermediate 11A) (49 mg, 0.11 mmol) and dimethylamine hydrochloride (18.2 mg, 0.22 mmol) were weighed into a round bottomed flask and dichloromethane (1 mL) added to form a suspension. Triethylamine (33.8 mg, 0.33 mmol) was added and the suspension stirred for 5 minutes before dropwise addition of 1-propanephosphonic acid cyclic anhydride as a 50% wt solution in ethyl acetate (107 mg, 0.17 mmol) and the resulting reaction mixture stirred for 2 hours. Reaction mixture was washed with sodium bicarbonate solution and the organics were separated using a hydrophobic frit. The solvent was removed under reduced pressure and then re-dissolved in methanol (1 mL) and purified by preparative-HPLC. To afford the title compound 2-(6-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-2-(3-chlorophenyl)-4-oxoquinazolin-3(4H)-yl)-N,N-dimethylacetamide (5.4 mg, 0.012 mmol).

Workup

  1. customto form a suspension
  2. customthe resulting reaction mixture
  3. customReaction mixture
  4. washwas washed with sodium bicarbonate solution
  5. customthe organics were separated
  6. customThe solvent was removed under reduced pressure
  7. dissolutionre-dissolved in methanol (1 mL)
  8. custompurified by preparative-HPLC

Sources & evidence

ORD record
ord-3331de4b5a144a7194d0527a54f57d0e
Source dataset
uspto-grants-2014_09
Patent number
US08841289B2

Reaction notes

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