Trifluoroacetic acid → HCID 11670461, compound

HRID 1444594Notes

Reaction equation

HRID 1444594 reaction equation
FC(F)(F)C(O)=O.C([O:12][C:13]([N:15]1[CH2:35][CH2:34][C:18]2[N:19]=[C:20]([NH:23][C:24](=[O:33])[C:25]3[CH:30]=[C:29]([Cl:31])[CH:28]=[C:27]([Cl:32])[CH:26]=3)[N:21]=[CH:22][C:17]=2[CH2:16]1)=O)(C)(C)C.CCN(C(C)C)C(C)C.[F:45][C:46]([F:57])([F:56])[C:47]1[CH:48]=[C:49]([CH:53]=[CH:54][CH:55]=1)C(O)=O.CCN=C=NCCCN(C)C.C1C=NC2N(O)N=NC=2C=1>C(Cl)Cl>[Cl:32][C:27]1[CH:26]=[C:25]([CH:30]=[C:29]([Cl:31])[CH:28]=1)[C:24]([NH:23][C:20]1[N:21]=[CH:22][C:17]2[CH2:16][N:15]([C:13](=[O:12])[C:54]3[CH:53]=[CH:49][CH:48]=[C:47]([C:46]([F:57])([F:56])[F:45])[CH:55]=3)[CH2:35][CH2:34][C:18]=2[N:19]=1)=[O:33]

Participants

8

Reactant 6

HCID 6422Trifluoroacetic acidHCID 99633-(Trifluoromethyl)benzoic acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 68679610HCID 68679610, compound

Product 1

HCID 11670461HCID 11670461, compoundYield 55.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Trifluoroacetic acid 5.0 ml (65 mmol) was added to a solution of 2-(3,5-dichloro-benzoylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic acid tert-butyl ester 404 mg (0.954 mmol) in CH2Cl2 (7 ml) under nitrogen as inert gas and stirring was performed for 2 h at RT. After removal of the solvent, the intermediate (3,5-dichloro-N-(5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)-benzamide trifluoroacetate) was dissolved in CH2Cl2 (10 ml) and DIPEA 340 μl and 3-trifluoromethylbenzoic acid 200 mg (1.05 mmol) were added. After cooling the reaction mixture to 0° C., EDCI 201 mg (1.05 mmol) and HOAt 20 mg (0.15 mmol) were added. The reaction mixture was stirred for 1 h at 0° C. and then overnight at RT. After removal of the solvent, purification was performed by means of column chromatography and the product 3,5-dichloro-N-[6-(3-trifluoromethyl-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide 260 mg (0.53 mmol, 55% of theoretical) was obtained.

Workup

  1. customAfter removal of the solvent
  2. dissolutionthe intermediate (3,5-dichloro-N-(5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)-benzamide trifluoroacetate) was dissolved in CH2Cl2 (10 ml)
  3. stirringThe reaction mixture was stirred for 1 h at 0° C.
  4. customovernight
  5. customat RT
  6. customAfter removal of the solvent, purification

Sources & evidence

ORD record
ord-e8035e7ac7494b53ab285101543a1113
Source dataset
uspto-grants-2010_02
Patent number
US07662828B2

Reaction notes

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