Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[CH:5][CH:4]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[NH2:27][CH2:28][C:29]1[CH:30]=[C:31]2[C:36](=[CH:37][CH:38]=1)[N:35]=[C:34]([CH3:39])[N:33]([CH:40]1[CH2:45][CH2:44][C:43](=[O:46])[NH:42][C:41]1=[O:47])[C:32]2=[O:48]>CN(C=O)C>[O:47]=[C:41]1[CH:40]([N:33]2[C:32](=[O:48])[C:31]3[C:36](=[CH:37][CH:38]=[C:29]([CH2:28][NH:27][C:7](=[O:9])[C:6]4[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:13])[F:12])=[CH:11][CH:10]=4)[CH:30]=3)[N:35]=[C:34]2[CH3:39])[CH2:45][CH2:44][C:43](=[O:46])[NH:42]1
Reactant: Cc1nc2ccc(CN)cc2c(=O)n1C1CCC(=O)NC1=O
Reactant: O=C(O)c1ccc(C(F)(F)F)cc1
Agent: Cl
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: CN(C)C=O
Product: Cc1nc2ccc(CNC(=O)c3ccc(C(F)(F)F)cc3)cc2c(=O)n1C1CCC(=O)NC1=O
Reaction time: 1 h
Yield: 66.1 %

Procedure:
To a stirred solution of 4-trifluoromethyl-benzoic acid (0.30 g, 1.6 mmol) in DMF (8 mL) in a 40° C. oil bath, was added 1,1′ carbonyldiimidazole (0.29 g, 1.8 mmol), and the mixture was stirred for one hour. Then 3-(6-aminomethyl-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione hydrogen chloride (0.54 g, 1.6 mmol) was added, and the mixture was stirred for 15 minutes. The solvent was evaporated, and the residue was purified by flash column chromatography (Silica gel, methanol/methylene chloride 4%/96%) to give N-[3-(2,6-dioxo-piperidin-3-yl)-2-methyl-4-oxo-3,4-dihydro-quinazolin-6-ylmethyl]-4-trifluoromethyl-benzamide as an off-white solid (500 mg, 67% yield); HPLC, Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 10/90 CH3CN/0.1% H3PO4, grad. to 95/5 in 5 min, kept 5 min, 6.33 min (99.1%); mp, 221-223° C.; 1HNMR (DMSO-d6) 2.14-2.20 (m, 1H, CHH), 2.56-2.88 (m, 6H, CHCH2, CH3), 4.62 (d, J=5 Hz, 2H, CH2NH), 5.26 (dd, J=6, 11 Hz, 1H, CH), 7.59-8.11 (m, 7H, Ar), 9.40 (t, J=5 Hz, 1H, CH2NH), 11.02 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.90, 23.41, 30.60, 42.41, 56.53, 120.03, 123.90 (q, JC-F=253 Hz), 123.95, 125.36 (d, JC-F=3 Hz), 125.45 (d, JC-F=3 Hz), 126.65, 128.14, 131.23 (d, JC-F=31 Hz), 134.11, 137.83, 145.87, 154.64, 160.42, 165.12, 169.45, 172.59. LCMS MH=473; Anal Calcd For C23H19N4O4F3: C, 58.48; H, 4.05; N, 11.86; F, 12.06. Found: C, 58.36; H, 3.96; N, 11.75; F, 11.84.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:14])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][C:11](O)=[O:12]>C1COCC1>[OH:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][C:3]([O:2][CH3:1])=[O:14]
Reactant: COC(=O)CCCCCCCC(=O)O
Solvent: C1CCOC1
Product: COC(=O)CCCCCCCCO
Temperature: 25 °C
Reaction time: 4 h
Yield: 99 %

Procedure:
To prepare 4, a solution of nonanedioic acid monomethyl ester (3) (923 mg, 4.6 mmol) in dry THF (3 ml) at −20° C. was treated with 1 M BH3 in THF (4.6 ml, 4.6 mmol) over 10 minutes. After stirring at room temperature for 4 hours, the reaction was quenched with 0.77 M aqueous K2CO3 solution (10 ml) at 0° C. The product was extracted with diethyl ether (3×20 ml), washed with saturated aqueous NaCl solution, dried over Na2SO4, and concentrated in vacuum to afford methyl 9-hydroxynonanoate (4) (Kai K. et al., Tetrahedron 64:6760-69 (2008), which is hereby incorporated by reference in its entirety) (850 mg, 99% yield) as a colorless oil, which was used directly without any further purification. 1H NMR (400 MHz, chloroform-d1): δ 1.27-1.37 (8H, m), 1.50-1.66 (4H, m), 2.29 (2H, t, J=7.5 Hz), 3.62 (2H, t, J=6.5 Hz), 3.66 (3H, s). See FIG. 75C.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][CH:8]=1)#[N:2].[Cl:12][C:13]1[N:18]=[CH:17][C:16]([CH2:19][N+:20]2[C:25]([O-:26])=[C:24](I)[C:23](=[O:28])[N:22]3[CH:29]=[CH:30][CH:31]=[CH:32][C:21]=23)=[CH:15][CH:14]=1.F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.ClCCl.CO.O1CCOCC1>[Cl:12][C:13]1[N:18]=[CH:17][C:16]([CH2:19][N+:20]2[C:25]([O-:26])=[C:24]([C:5]3[CH:6]=[CH:7][CH:8]=[C:3]([C:1]#[N:2])[CH:4]=3)[C:23](=[O:28])[N:22]3[CH:29]=[CH:30][CH:31]=[CH:32][C:21]=23)=[CH:15][CH:14]=1
Reactant: N#Cc1cccc(B(O)O)c1
Reactant: O=c1c(I)c([O-])[n+](Cc2ccc(Cl)nc2)c2ccccn12
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)(C)[PH+](C(C)(C)C)C(C)(C)C
Solvent: C1COCCO1
Solvent: CO
Solvent: ClCCl
Product: N#Cc1cccc(-c2c([O-])[n+](Cc3ccc(Cl)nc3)c3ccccn3c2=O)c1
Temperature: 80 °C

Procedure:
To a mixture of 80 mg (0.54 mmol) (3-cyanophenyl)boronic acid, 150 mg (0.36 mmol) 1-[(6-chloro-3-pyridyl)methyl]-3-iodo-4-oxo-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Synthesis described in WO 2009/099929), 1.6 mg (0.07 mmol) palladium acetate, 21 mg (0.07 mmol) tri-tert-butylphosphonium tetrafluoroborate and 295 mg caesium carbonate was added 50 ml of dioxane under argon. The mixture was heated to 80° C. for 48 hours. Silica was added and the product was obtained by column chromatographie (dichloromethane/methanol) (21 mg).
Reaction SMILES: [CH3:1][N:2](C(OC(C)(C)C)=O)[CH:3]([CH2:5]/[CH:6]=[CH:7]/[C:8]1[CH:9]=[N:10][CH:11]=[C:12]([O:14][CH2:15][CH3:16])[CH:13]=1)[CH3:4].FC(F)(F)C(O)=O>C1(OC)C=CC=CC=1>[CH3:1][NH:2][CH:3]([CH2:5]/[CH:6]=[CH:7]/[C:8]1[CH:9]=[N:10][CH:11]=[C:12]([O:14][CH2:15][CH3:16])[CH:13]=1)[CH3:4]
Reactant: CCOc1cncc(/C=C/CC(C)N(C)C(=O)OC(C)(C)C)c1
Solvent: O=C(O)C(F)(F)F
Solvent: COc1ccccc1
Product: CCOc1cncc(/C=C/CC(C)NC)c1
Reaction time: 0.75 h
Yield: 99.9 %

Procedure:
Under a nitrogen atmosphere, a cold (0–5° C.), stirring solution of (4E)-N-methyl-N-(tert-butoxycarbonyl)-5-(5-ethoxy-3-pyridyl)-4-penten-2-amine (0.67 g, 2.09 mmol) in anisole (10 mL) was treated dropwise over 30 min with trifluoroacetic acid (10.40 g, 91.17 mmol). The resulting solution was stirred for 45 min at 0–5° C. and was then concentrated by rotary evaporation. The light-yellow oil was further dried under high vacuum at 0.5 mm Hg. The resulting oil was cooled (0–5° C.), basified with 10% NaOH solution (10 mL), treated with saturated NaCl solution (7.5 mL), and extracted with CHCl3 (4×10 mL). The combined light-yellow CHCl3 extracts were washed with saturated NaCl solution (20 mL), dried (Na2SO4), filtered, concentrated by rotary evaporation, followed by further drying at 0.5 mm Hg producing a brown oil (0.46 g). The crude product was purified by column chromatography on silica gel (56 g), eluting with CH3OH-Et3N (98:2, v/v). Selected fractions containing the product (Rf 0.35) were combined and concentrated on a rotary evaporator. The residue was dissolved in CHCl3, and the CHCl3 solution was dried (Na2SO4), filtered, concentrated by rotary evaporation, and vacuum dried to give 327.5 mg (71.0%) of a light-yellow oil.
Reaction SMILES: C[O-].[Na+].[CH2:4]([O:6][C:7]([CH2:9][N:10]([CH3:27])[S:11]([C:14]1[C:15]2[CH:26]=[CH:25][CH:24]=[CH:23][C:16]=2[S:17][C:18]=1[C:19](OC)=[O:20])(=[O:13])=[O:12])=[O:8])C>CO>[OH:20][C:19]1[C:18]2[S:17][C:16]3[CH:23]=[CH:24][CH:25]=[CH:26][C:15]=3[C:14]=2[S:11](=[O:13])(=[O:12])[N:10]([CH3:27])[C:9]=1[C:7]([O:6][CH3:4])=[O:8]
Reactant: CCOC(=O)CN(C)S(=O)(=O)c1c(C(=O)OC)sc2ccccc12
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: COC(=O)C1=C(O)c2sc3ccccc3c2S(=O)(=O)N1C
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
42.0 gm (0.78 mol) of solid sodium methylate were added in an inert gas atmosphere to a suspension of 286 gm (0.77 mol) of methyl 3-{[(ethoxycarbonylmethyl)-methylamino]sulfonyl}-benzo[b]thiophene-2-carboxylate in 1000 cc of anhydrous methanol. The mixture was stirred for 30 minutes at room temperature and then refluxed for 1 hour. The solvent was distilled off, and the residue was stirred into 500 ml of ice-cold 2 N hydrochloric acid. The precipitated product was filtered off, taken up in 400 cc of chloroform, and the solution was dried over sodium sulfate and evaporated in vacuo. After recrystallizing the residue twice from 100 cc each of methanol, 116 gm (46% of theory) of light-yellow crystals were obtained.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([O:7][N:8]=[C:9]2[CH2:14][CH2:13][N:12]([C:15]3[CH:20]=[C:19]([F:21])[C:18]([Br:22])=[CH:17][C:16]=3[F:23])[CH2:11][CH2:10]2)[CH2:3][CH2:2]1.Cl[C:25]1[N:30]=[CH:29][C:28]([CH2:31][CH3:32])=[CH:27][N:26]=1.C(N(C(C)C)CC)(C)C.O>CS(C)=O.CCOC(C)=O>[CH2:31]([C:28]1[CH:27]=[N:26][C:25]([N:1]2[CH2:6][CH2:5][CH:4]([O:7][N:8]=[C:9]3[CH2:14][CH2:13][N:12]([C:15]4[CH:20]=[C:19]([F:21])[C:18]([Br:22])=[CH:17][C:16]=4[F:23])[CH2:11][CH2:10]3)[CH2:3][CH2:2]2)=[N:30][CH:29]=1)[CH3:32]
Reactant: Fc1cc(N2CCC(=NOC3CCNCC3)CC2)c(F)cc1Br
Reactant: CCc1cnc(Cl)nc1
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Solvent: CS(C)=O
Product: CCc1cnc(N2CCC(ON=C3CCN(c4cc(F)c(Br)cc4F)CC3)CC2)nc1

Procedure:
Compound 77b and 2-chloro-5-ethyl-pyrimidine (300 mg) were heated with diisopropylethylamine (300 mg) in DMSO at 130° C. for 0.5 h. Water and EtOAc were added and the organic phase separated, dried over MgSO4 and concentrated. The mixture was purified by chromatography on silica gel eluting with EtOAc/Hexane to give 1-(4-bromo-2,5-difluoro-phenyl)-piperidin-4-one O-[1-(5-ethyl-pyrimidin-2-yl)-piperidin-4-yl]-oxime 77c (170 mg).
Reaction SMILES: [CH3:1][N:2]1[CH2:6][C:5]2[CH:7]=[CH:8][C:9]3[C:13](=[O:14])[C:12](=[O:15])[NH:11][C:10]=3[C:4]=2[CH2:3]1.[Br:16]Br.C([O-])([O-])=O.[Na+].[Na+]>O.C(O)C>[Br:16][C:7]1[C:5]2[CH2:6][N:2]([CH3:1])[CH2:3][C:4]=2[C:10]2[NH:11][C:12](=[O:15])[C:13](=[O:14])[C:9]=2[CH:8]=1
Reactant: CN1Cc2ccc3c(c2C1)NC(=O)C3=O
Reactant: BrBr
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: CN1Cc2c(Br)cc3c(c2C1)NC(=O)C3=O
Temperature: 25 °C
Reaction time: 5 h

Procedure:
To a stirred suspension of 1,6,7,8-tetrahydro-7-methylbenzo[2,1-b:3,4-c']dipyrrole-2,3-dione (0.5 g, 2.48 mmol) in water (20 ml) was added a solution of bromine (0.7 ml) in ethanol (5 ml). After 5 hours stirring at room temperature the reaction was completed and pH was adjusted to 8 with sat Na2CO3. The precipitated product was filtered off and washed with water, M.p. >300° C.
Reaction SMILES: [C:1]([C:4]1[CH:11]=[CH:10][C:7]([C:8]#[N:9])=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[Cl-].[Al+3].[Cl-].[Cl-].[Br:16]Br>CCOCC>[C:8]([C:7]1[CH:10]=[CH:11][C:4]([C:1](=[O:3])[CH2:2][Br:16])=[CH:5][CH:6]=1)#[N:9]
Reactant: BrBr
Reactant: CC(=O)c1ccc(C#N)cc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: CCOCC
Product: N#Cc1ccc(C(=O)CBr)cc1
Reaction time: 0.5 h

Procedure:
4-Acetylbenzonitrile (14.5 g, 100 mmol) was dissolved in anhydrous ether (150 ml). Aluminium chloride (catalytic amount) was added to the solution. Bromine (5.1 ml, 100 mmol) was added dropwise at room temperature and the solution stirred for 1/2 h. A precipitate formed and was collected and dried to yield p-cyanophenacyl bromide, m.p. 85°-86° C. (19.34 g, 86%); δH (CDCl3) 7.80 and 8.10 (4H, ABq, aryl), 4.45 (2H, s, CH2).
Reaction SMILES: [C:1]1([CH3:46])[C:2]([C:7]([CH2:9][N:10]2[C:16]3[CH:17]=[C:18]([CH3:21])[CH:19]=[CH:20][C:15]=3[N:14]([C:22]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=3)=[O:23])[CH2:13][CH:12]([NH:30][C:31]([NH:33][C:34]3[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([O:42]CC)=[O:41])[CH:35]=3)=[O:32])[C:11]2=[O:45])=[O:8])=[CH:3][CH:4]=[CH:5][CH:6]=1.O.[OH-].[Li+].O1CCCC1>CO>[C:1]1([CH3:46])[C:2]([C:7]([CH2:9][N:10]2[C:16]3[CH:17]=[C:18]([CH3:21])[CH:19]=[CH:20][C:15]=3[N:14]([C:22]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=3)=[O:23])[CH2:13][CH:12]([NH:30][C:31](=[O:32])[NH:33][C:34]3[CH:35]=[C:36]([CH:37]=[CH:38][CH:39]=3)[C:40]([OH:42])=[O:41])[C:11]2=[O:45])=[O:8])=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CCOC(=O)c1cccc(NC(=O)NC2CN(C(=O)c3ccccn3)c3ccc(C)cc3N(CC(=O)c3ccccc3C)C2=O)c1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Solvent: C1CCOC1
Product: Cc1ccc2c(c1)N(CC(=O)c1ccccc1C)C(=O)C(NC(=O)Nc1cccc(C(=O)O)c1)CN2C(=O)c1ccccn1
Yield: 45.6 %

Procedure:
1-[1-(2-Toluoylmethy)-2-oxo-5-(2-pyridylcarbonyl)-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-ethoxycarbonylphenyl)urea (466 mg) was dissolved in methanol (22 ml), aqueous lithium hydroxide monohydrate (158 mg) solution (11 mg) and tetrahydrofuran (11 ml) were added, and the mixture was refluxed for one hour. The reaction mixture was concentrated under reduced pressure, the residue was dissolved in water, the solution was washed with diethyl ether, acidified with 1N hydrochloric acid, and extracted with methylene chloride. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. Isopropyl ether was added to the residue for trituration, collected by filtration, to thereby obtain 203 mg of the titled compound.
Reaction SMILES: [OH:1]O.[CH:3]1[C:8]([OH:9])=[CH:7][CH:6]=[C:5]([CH3:10])[CH:4]=1>O>[CH3:10][C:5]1[CH:4]=[C:3]([OH:1])[C:8](=[CH:7][CH:6]=1)[OH:9]
Reactant: Cc1ccc(O)cc1
Reactant: OO
Solvent: O
Product: Cc1ccc(O)c(O)c1
Reaction time: 0.25 h
Yield: 65.1 %

Procedure:
A water-free solution of 3.40 grams of H2O2 (0.1 mole) in 108.1 grams (1.0 mole) of p-cresol was heated to 95° C. and treated with 0.018 gram (0.00015 mole) of SeO2. The temperature increased in connection therewith to 161° C. After 15 minutes there was determined a hydrogen peroxide reaction of 99.4%. At that time there were formed in the reaction mixture 8.08 grams of 4-methylpyrocatechol, which corresponds to a yield of 65.5 mole %, based on the reacted H2O2. 4-Methylresorcinol was formed in an amount of 0.85 mole %.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[C:10]([N:11](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)=[N:9][CH:8]=[C:7]([CH2:26][CH:27]([CH3:29])[CH3:28])[N:6]=1)=[O:4].FC(F)(F)C(O)=O.CCCCCCC.C(OCC)(=O)C>ClCCl>[CH3:1][O:2][C:3]([C:5]1[C:10]([NH2:11])=[N:9][CH:8]=[C:7]([CH2:26][CH:27]([CH3:29])[CH3:28])[N:6]=1)=[O:4]
Reactant: COC(=O)c1nc(CC(C)C)cnc1N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Solvent: CCCCCCC
Product: COC(=O)c1nc(CC(C)C)cnc1N
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of 3-(bis(tert-butoxycarbonyl)amino)-6-isobutylpyrazine-2-carboxylic acid methyl ester (201 mg, 442 μmol) in dichloromethane (4 mL) was added trifluoroacetic acid (511 μL, 6.63 mmol) at room temperature. The mixture was stirred at ambient temperature for 3 h and the volatiles were evaporated. The residue was dissolved in dichloromethane (50 mL) and extracted with sodium carbonate. The aqueous phase was washed with dichloromethane and the organic layers were dried and evaporated. The product was obtained after silica gel chromatography using a heptane/ethyl acetate gradient as light yellow solid (88 mg, 95%).
Reaction SMILES: Br[C:2]1[N:10]2[C:5]([CH:6]=[N:7][C:8]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)=[CH:14][CH:13]=3)=[N:9]2)=[CH:4][CH:3]=1.CC(C)([O-])C.[Na+].C(O)CO.CN(C)C=O.[C:40]1([SH:46])[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>[Cu]I>[CH3:24][N:21]1[CH2:22][CH2:23][N:18]([C:15]2[CH:16]=[CH:17][C:12]([NH:11][C:8]3[N:7]=[CH:6][C:5]4=[CH:4][CH:3]=[C:2]([S:46][C:40]5[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=5)[N:10]4[N:9]=3)=[CH:13][CH:14]=2)[CH2:19][CH2:20]1
Reactant: CN1CCN(c2ccc(Nc3ncc4ccc(Br)n4n3)cc2)CC1
Reactant: Sc1ccccc1
Agent: [Cu]I
Agent: CC(C)(C)[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: OCCO
Product: CN1CCN(c2ccc(Nc3ncc4ccc(Sc5ccccc5)n4n3)cc2)CC1
Temperature: 120 °C
Yield: 27.1 %

Procedure:
Into a sealed tube was added (7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine (0.120 g, 0.310 mmol), Sodium tert-butoxide (89.5 mg, 0.931 mmol), Copper(I) iodide (4 mg, 0.02 mmol), 1,2-Ethanediol (34.7 uL, 0.623 mmol), N,N-Dimethylformamide (4.4 mL, 56 mmol), and finally Benzenethiol (32.1 uL, 0.313 mmol). The reaction was heated at 120° C. overnight. An HPLC showed 40% starting material remaining The reaction was partitioned with water and DCM. The organic was separated, washed with Brine and dried over Na2SO4. The solid was filtered and washed with DCM. The Solvent was removed under vacuum. The desired product was purified via ISCO column chromatography with DCM and methanol as eluant (0 to 8% methanol). The collected fractions afforded [4-(4-Methyl-piperazin-1-yl)-phenyl]-(7-phenylsulfanyl-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-amine as a yellow solid (35 mg, 27%). MP 155-157° C. LCMS (E/I+) 417.13 (M+H). NMR 1H (DSMO-d6)-9.33 (s, 1H), 8.97 (s, 1H), 7.43 (d, 2H, J=9.04 Hz), 7.30 (t, 2H, J=7.57 Hz), 7.18 (t, 1H, J=7.33 Hz), 7.13 (d, 2H, J=8.33 Hz), 7.01 (d, 1H, J=4.60 Hz), 6.92 (d, 1H, J=4.60 Hz), 6.74 (d, 2H, J=9.09 Hz), 3.03 (t, 4H, J=5.96 Hz), 2.44 (t, 4H, J=5.21 Hz), 2.23 (s, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH:12]([CH3:14])[CH3:13])[C:10](=[O:15])[C@@H:9]([CH2:16]/[CH:17]=[CH:18]/[C:19]([OH:21])=[O:20])[O:8][C@H:7]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[Cl:28])[C:6]=2[CH:29]=1.[H][H]>C(OCC)(=O)C.[C].[Pd]>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH:12]([CH3:13])[CH3:14])[C:10](=[O:15])[C@@H:9]([CH2:16][CH2:17][CH2:18][C:19]([OH:21])=[O:20])[O:8][C@H:7]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[Cl:28])[C:6]=2[CH:29]=1
Reactant: [H][H]
Reactant: CC(C)N1C(=O)[C@@H](C/C=C/C(=O)O)O[C@H](c2ccccc2Cl)c2cc(Cl)ccc21
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CC(C)N1C(=O)[C@@H](CCCC(=O)O)O[C@H](c2ccccc2Cl)c2cc(Cl)ccc21
Yield: 81.8 %

Procedure:
In ethyl acetate (20 ml) was dissolved ethyl ester of trans-7-chloro-5-(2-chlorophenyl)-1-isopropyl-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-crotonic acid (0.45 g). To the solution was added 10% palladium carbon (0.1 g), and the mixture was subjected to catalytic reduction at room temperatures under atmospheric pressure. The theoretical amount of hydrogen was allowed to be absorbed, then the catalyst was removed, followed by distilling off ethyl acetate under reduced pressure. The residue was crystallized from a small volume of hexane to give ethyl ester of trans-7-chloro-5-(2-chlorophenyl)-1-isopropyl-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-butyric acid (0.37 g) as prisms, m.p.100°-101° C.
Reaction SMILES: [CH3:1][C@@:2]1([C:18]([F:21])([F:20])[F:19])[CH2:17][N:5]2[C:6](=[O:16])[CH:7]=[C:8]([N:10]3[CH2:15][CH2:14][O:13][CH2:12][CH2:11]3)[N:9]=[C:4]2[NH:3]1.[Br:22][C:23]1[CH:28]=[C:27]([CH2:29]Br)[CH:26]=[CH:25][C:24]=1[F:31].C(=O)([O-])[O-].[Cs+].[Cs+]>>[Br:22][C:23]1[CH:28]=[C:27]([CH:26]=[CH:25][C:24]=1[F:31])[CH2:29][N:3]1[C:4]2=[N:9][C:8]([N:10]3[CH2:11][CH2:12][O:13][CH2:14][CH2:15]3)=[CH:7][C:6](=[O:16])[N:5]2[CH2:17][C@@:2]1([CH3:1])[C:18]([F:21])([F:19])[F:20]
Reactant: C[C@@]1(C(F)(F)F)Cn2c(nc(N3CCOCC3)cc2=O)N1
Reactant: Fc1ccc(CBr)cc1Br
Agent: O=C([O-])[O-]
Agent: [Cs+]
Product: C[C@@]1(C(F)(F)F)Cn2c(nc(N3CCOCC3)cc2=O)N1Cc1ccc(F)c(Br)c1

Procedure:
The product is prepared according to the procedure described in stage k of Example 1, using 100 mg of (2S)-2-methyl-7-(morpholin-4-yl)-2-(trifluoromethyl)-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one (Example 1j) and 106 mg of 2-bromo-4-(bromomethyl)-1-fluorobenzene, replacing the sodium hydride with 214 mg of caesium carbonate. After purification by preparative HPLC/MS (method C), 50 mg of (2S)-1-(3-bromo-4-fluorobenzyl)-2-methyl-7-(morpholin-4-yl)-2-(trifluoromethyl)-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one are obtained in the form of a off-white semi-solid, the characteristics of which are the following:
Reaction SMILES: [CH:1]1([C:7]2([CH:36]3[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]3)[CH:11]3[CH2:12][N:13](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[CH2:14][CH2:15][N:10]3[C:9](=[O:35])[O:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.C(OCC)(=O)C>O1CCCC1>[CH:36]1([C:7]2([CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]3)[CH:11]3[CH2:12][NH:13][CH2:14][CH2:15][N:10]3[C:9](=[O:35])[O:8]2)[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1
Reactant: O=C1OC(C2CCCCC2)(C2CCCCC2)C2CN(C(c3ccccc3)(c3ccccc3)c3ccccc3)CCN12
Agent: Cl
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: O=C1OC(C2CCCCC2)(C2CCCCC2)C2CNCCN12
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 78.7 %

Procedure:
To a solution of hexahydro-1,1-dicyclohexyl-7-(triphenylmethyl)-3H-oxazolo[3,4-a]pyrazin-3-one (0.92 g, 1.7 mmol) in tetrahydrofuran (5 mL) was added a 4 M hydrogen chloride/ethyl acetate solution (5 mL) with ice cooling, and the mixture was stirred at room temperature for 2.5 hours. The reaction solution was concentrated under reduced pressure, water was then added thereto and washed with diethyl ether. To the aqueous layer was added sodium hydrogen carbonate, and the mixture was adjusted to pH 7 and then extracted with ethyl acetate. The extract was washed with water and concentrated under reduced pressure. The precipitated crystals were washed with hexane and dried to obtain the title compound (0.41 g, yield 80%).
Reaction SMILES: [F:1][C:2]([F:17])([F:16])[CH:3]([C:5]1[CH:10]=[CH:9][C:8]([O:11][C:12]([F:15])([F:14])[F:13])=[CH:7][CH:6]=1)[OH:4].Cl[O-].[Na+].O>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.C(Cl)Cl>[F:1][C:2]([F:16])([F:17])[C:3]([C:5]1[CH:10]=[CH:9][C:8]([O:11][C:12]([F:13])([F:14])[F:15])=[CH:7][CH:6]=1)=[O:4]
Reactant: OC(c1ccc(OC(F)(F)F)cc1)C(F)(F)F
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=S(=O)([O-])O
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Product: O=C(c1ccc(OC(F)(F)F)cc1)C(F)(F)F

Procedure:
24.0 g (0.09 mol) of 2,2,2-trifluoro-1-(4-trifluoromethoxyphenyl)ethanol and 1.57 g (0.0046 mol) of tetrabutylammonium hydrogen sulfate are dissolved in 250 ml of methylene chloride at room temperature. 100 ml (0.12 mol) of an approximately 12% strength sodium hypochlorite solution are metered in within 20 minutes with vigorous stirring and the mixture is stirred for a further 5 hours during which the temperature rises to 40° C. The reaction mixture is added to 400 ml of water, the phases are separated, the aqueous phase is extracted several times with methylene chloride and the combined organic phases are washed with saturated aqueous sodium chloride solution. After drying the organic phase with sodium sulfate, the volatiles are distilled off. Following distillation of the crude product in a kugelrohr (14 torr, bath temperature 100°-115° C.), 17.19 g (74% of theory) of 4-trifluoroacetyltrifluoromethoxybenzene are obtained. nD20 : 1.4188.
Reaction SMILES: COC(=O)[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([NH:10][C:11](=[O:38])[CH2:12][N:13]2[N:19]=[C:18]([CH:20]3[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]3)[C:17]3[CH:26]=[CH:27][CH:28]=[CH:29][C:16]=3[N:15]([CH2:30][C:31](=[O:36])[C:32]([CH3:35])([CH3:34])[CH3:33])[C:14]2=[O:37])[CH:5]=1.O=C1N(CC(O)=O)N=C(C2C=CC=CN=2)C2C=CC=CC=2N1CC(=O)N1CCCC1.[C:70]([O:74][C:75](=[O:85])[N:76](C1C=CC=C(N)C=1)[CH3:77])([CH3:73])([CH3:72])[CH3:71].C1(C2C3C=CC=CC=3N(CC(=O)C(C)(C)C)C(=O)N(CC(O)=O)N=2)CCCCC1.COC(=O)C1C=CC=C(N)C=1>>[C:70]([O:74][C:75](=[O:85])[N:76]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([NH:10][C:11](=[O:38])[CH2:12][N:13]2[N:19]=[C:18]([CH:17]3[CH2:16][CH2:29][CH2:28][CH2:27][CH2:26]3)[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:25]=3[N:15]([CH2:30][C:31](=[O:36])[C:32]([CH3:34])([CH3:35])[CH3:33])[C:14]2=[O:37])[CH:5]=1)[CH3:77])([CH3:73])([CH3:72])[CH3:71]
Reactant: COC(=O)c1cccc(NC(=O)CN2N=C(C3CCCCC3)c3ccccc3N(CC(=O)C(C)(C)C)C2=O)c1
Reactant: CN(C(=O)OC(C)(C)C)c1cccc(N)c1
Agent: CC(C)(C)C(=O)CN1C(=O)N(CC(=O)O)N=C(C2CCCCC2)c2ccccc21
Agent: COC(=O)c1cccc(N)c1
Agent: O=C(O)CN1N=C(c2ccccn2)c2ccccc2N(CC(=O)N2CCCC2)C1=O
Product: CN(C(=O)OC(C)(C)C)c1cccc(NC(=O)CN2N=C(C3CCCCC3)c3ccccc3N(CC(=O)C(C)(C)C)C2=O)c1

Procedure:
The title compound was obtained by the method used in the preparation of 3-{2-[5-cyclohexyl-1-(3,3-dimethyl-2-oxo-butyl)-2-oxo-1,2-dihydro-3H-1,3,4-benzotriazepin-3-yl]-acetylamino}-benzoic acid methyl ester (Example 1, step e) except that [2-oxo-1-(2-oxo-2-pyrrolidin-1-yl-ethyl)-5-pyridin-2-yl-1,2-dihydro-3H-1,3,4-benzotriazepin-3-yl]-acetic acid (Example 6, step a) and (3-amino-phenyl)-methyl-carbamic acid tert-butyl ester (Example 3, step c) were used in place of [5-cyclohexyl-1-(3,3-dimethyl-2-oxo-butyl)-2-oxo-1,2-dihydro-3H-1,3,4-benzotriazepin-3-yl]-acetic acid (Example 1, step d) and 3-amino-benzoic acid methyl ester respectively, followed by reaction of the product obtained, in place of (3-{2-[5-cyclohexyl-1-(3,3-dimethyl-2-oxo-butyl)-2-oxo-1,2-dihydro-3H-1,3,4-benzotriazepin-3-yl]-acetylamino}-phenyl)-methyl-carbamic acid tert-butyl ester (Example 3, step d), according to the method of Example 3, step e. 1H NMR (CDCl3) 8.61 (1H, d), 8.07 (2H, m), 7.77 (1H, dt), 7.54 (2H, m), 7.36-7.24 (3H, m), 6.98 (1H, t), 6.88 (1H, s), 6.48 (1H, d), 6.28 (1H, d), 4.53-4.34 (4H, br m), 3.52-3.20 (5H, br m), 2.75 (3H, s), 1.97 (2H, m), 1.87 (2H, m). Found: C, 65.44; H, 6.00; N, 18.79%; C28H29N7O3 requires: C, 65.74; H, 5.71; N, 19.17%.