Triethylamine → (5,11-Dihydro-pyrido[2,3-b][1,5]benzodiazepin-6-yl)-[4-(3-methyl-pyrazol-1-yl)-2-trifluoromethyl-phenyl]-methanone

HRID 1978183Notes

Reaction equation

HRID 1978183 reaction equation
[CH3:1][C:2]1[CH:6]=[CH:5][N:4]([C:7]2[CH:15]=[CH:14][C:10]([C:11]([OH:13])=O)=[C:9]([C:16]([F:19])([F:18])[F:17])[CH:8]=2)[N:3]=1.C(N(CC)CC)C.ClC1C=C(Cl)C=C(Cl)C=1C(Cl)=O.[N:39]1[C:44]2[NH:45][C:46]3[CH:53]=[CH:52][CH:51]=[CH:50][C:47]=3[NH:48][CH2:49][C:43]=2[CH:42]=[CH:41][CH:40]=1.C(=O)(O)[O-].[Na+]>ClCCl.CN(C)C1C=CN=CC=1>[CH3:1][C:2]1[CH:6]=[CH:5][N:4]([C:7]2[CH:15]=[CH:14][C:10]([C:11]([N:48]3[C:47]4[CH:50]=[CH:51][CH:52]=[CH:53][C:46]=4[NH:45][C:44]4[N:39]=[CH:40][CH:41]=[CH:42][C:43]=4[CH2:49]3)=[O:13])=[C:9]([C:16]([F:19])([F:18])[F:17])[CH:8]=2)[N:3]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 27337032,4,6-Trichlorobenzoyl chlorideHCID 110307606,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepineHCID 155410864-(3-Methyl-1H-pyrazol-1-yl)-2-trifluoromethylbenzoic acid

Product 1

HCID 9824954(5,11-Dihydro-pyrido[2,3-b][1,5]benzodiazepin-6-yl)-[4-(3-methyl-pyrazol-1-yl)-2-trifluoromethyl-phenyl]-methanoneYield 58.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(3-methyl-1H-pyrazol-1-yl)-2-trifluoromethyl benzoic acid (1.1 g, 4.1 mmole) of Step C, and triethylamine (0.57 mL, 4.1 mmol) in dichloromethane (20 mL) was added 2,4,6-trichlorobenzoyl chloride (0.63 mL, 4.0 mmol). After stirring for 5.5 hours, 6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine of Example 1, Step B (0.67 g, 3.4 mmol) and 4-dimethylamino pyridine (0.42 g, 3.4 mmol) were added. After stirring for an additional 18 hours, the mixture was poured into saturated aqueous sodium bicarbonate. The organic phase was washed with brine, dried over sodium sulfate, and evaporated to dryness. The residue was dissolved in dichloromethane and absorbed onto a silica Merck-60 flash column. Elution with hexane-ethyl acetate (gradient from 8:2 to 7:3) provided the title product (0.89 g) as a foam which crystallized by sonication from ethanol-hexane, m.p. 212-214° C. This material was identical to the compound of Example 4, Step C.

Workup

  1. stirringAfter stirring for an additional 18 hours
  2. washThe organic phase was washed with brine
  3. dry with materialdried over sodium sulfate
  4. customevaporated to dryness
  5. dissolutionThe residue was dissolved in dichloromethane
  6. customabsorbed onto a silica Merck-60 flash column
  7. washElution with hexane-ethyl acetate (gradient from 8:2 to 7:3)

Sources & evidence

ORD record
ord-89c3cf9e0da54b999cfe9816608d0c5a
Source dataset
uspto-grants-2001_05
Patent number
US06235900B1

Reaction notes

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