Phosgene → HCID 86622753, compound

HRID 1020254Notes

Reaction equation

HRID 1020254 reaction equation
[C:1](Cl)(Cl)=[O:2].[CH2:5]([NH2:15])[C:6]1[CH:14]=[CH:13][C:12]2[O:11][CH2:10][O:9][C:8]=2[CH:7]=1.CCN(C(C)C)C(C)C.Cl.[NH2:26][C:27]1[S:28][CH:29]=[C:30]([CH2:32][Cl:33])[N:31]=1>C1(C)C=CC=CC=1.C1COCC1>[O:11]1[C:12]2[CH:13]=[CH:14][C:6]([CH2:5][NH:15][C:1]([NH:26][C:27]3[S:28][CH:29]=[C:30]([CH2:32][Cl:33])[N:31]=3)=[O:2])=[CH:7][C:8]=2[O:9][CH2:10]1

Participants

7

Reactant 4

HCID 6371PhosgeneHCID 732282-Thiazolamine, 4-(chloromethyl)-, hydrochloride (1:1)HCID 75799Benzo-1,3-dioxole-5-methylamineHCID 81531Diisopropylethylamine

Product 1

HCID 86622753HCID 86622753, compoundYield 32%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

Phosgene (54.0 mmol, 27.9 mL of a 1.93 M solution in toluene) was placed in a 3-neck-flask and cooled to 0° C. THF (10 mL) was added, followed by a mixture of piperonylamine (27.0 mmol, 4.0 g) and DIPEA (56.7 mmol, 7.3 g) in THF (20 mL) at 0° C. After complete addition the mixture was stirred for another 40 min at 0° C. The reaction mixture was then concentrated. To the crude material THF (40 mL) and DIPEA (4.4 mL) were added. This mixture was then added to a slurry of 2-amino-4-(chloromethyl)thiazole hydrochloride (24.3 mmol, 4.5 g) in THF (50 mL). After stirring for 72 h at room temperature the reaction mixture was filtered through celite. The celite was washed with ethylacetate. The combined filtrate was concentrated and the material was directly applied to column chromatography (MeOH/DCM) providing 2.6 g (32%) of the desired intermediate. 1H-NMR (CD3OD, 300 MHz) δ 6.96 (s, 1H), 6.79 (m, 3H), 5.91 (s, 2H), 4.55 (s, 2H), 4.32 (s, 2H).

Workup

  1. additionAfter complete addition the mixture
  2. concentrationThe reaction mixture was then concentrated
  3. additionTo the crude material THF (40 mL) and DIPEA (4.4 mL) were added
  4. stirringAfter stirring for 72 h at room temperature the reaction mixture
  5. filtrationwas filtered through celite
  6. washThe celite was washed with ethylacetate
  7. concentrationThe combined filtrate was concentrated

Sources & evidence

ORD record
ord-28eb8805f86249919c7ce0ac8acb8224
Source dataset
uspto-grants-2014_05
Patent number
US08716320B2

Reaction notes

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