Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][CH2:5][C:6]([N:8]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[C:12](=[O:19])[CH2:11][CH2:10][CH2:9]1)=[O:7].[C:20]([C:24]1[N:29]=[C:28]([N:30]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)[CH:27]=[C:26]([C:36]([F:39])([F:38])[F:37])[N:25]=1)([CH3:23])([CH3:22])[CH3:21].[Na+].[Br-].C(N(C(C)C)CC)(C)C>CN1CCCC1=O>[C:20]([C:24]1[N:29]=[C:28]([N:30]2[CH2:31][CH2:32][N:33]([CH2:2][CH2:3][CH2:4][CH2:5][C:6]([N:8]3[C:14]4[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=4[C:12](=[O:19])[CH2:11][CH2:10][CH2:9]3)=[O:7])[CH2:34][CH2:35]2)[CH:27]=[C:26]([C:36]([F:37])([F:38])[F:39])[N:25]=1)([CH3:23])([CH3:21])[CH3:22]
Reactant: CC(C)(C)c1nc(N2CCNCC2)cc(C(F)(F)F)n1
Reactant: O=C1CCCN(C(=O)CCCCCl)c2ccccc21
Agent: [Br-]
Agent: [Na+]
Solvent: CN1CCCC1=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)c1nc(N2CCN(CCCCC(=O)N3CCCC(=O)c4ccccc43)CC2)cc(C(F)(F)F)n1
Yield: 40.8 %

Procedure:
1-(5-Chloropentanoyl)-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one from Example 12a (1.43 mmol, 0.50 g), 2-tert-butyl-4-piperazin-1-yl-6-(trifluoromethyl)pyrimidine (1.43 mmol, 0.41 g, preparation according to DE 19735410), NaBr (7.14 mmol, 0.74 g), DIPEA (diisopropylethylamine) (14.01 mmol, 1.81 g) and N-methylpyrrolidinone (0.6 ml) were heated to 120° C. for 5 h. Subsequently, the reaction mixture was filtered and the resulting filtrate was concentrated to dryness. Afterward, ethyl acetate was added to the resulting residue and it was washed with saturated, aqueous sodium chloride solution. The organic phase was dried and then concentrated to dryness. The residue was purified by chromatography on silica gel, eluent: methyl tert-butyl ether/methanol (0-100%); to obtain 0.31 g of the title compound.
Reaction SMILES: [C:1](Cl)(=[O:5])[CH2:2][CH2:3][CH3:4].[F:7][C:8]([F:20])([F:19])[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[C:12]2[NH2:18]>N1C=CC=CC=1>[F:20][C:8]([F:7])([F:19])[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[C:12]2[NH:18][C:1](=[O:5])[CH2:2][CH2:3][CH3:4]
Reactant: Nc1n[nH]c2ccc(C(F)(F)F)cc12
Reactant: CCCC(=O)Cl
Solvent: c1ccncc1
Product: CCCC(=O)Nc1n[nH]c2ccc(C(F)(F)F)cc12
Reaction time: 12 h

Procedure:
0.26 cm3 of butyryl chloride is added to 500 mg of 5-(trifluoromethyl)-1H-indazole-3-amine, prepared according to patent U.S. Pat. No. 3,133,081, in 15 cm3 of pyridine, and cooled to about 5° C. The reaction medium is allowed to return to about 19° C. over 12 hours. The reaction medium is evaporated under reduced pressure (2 kPa; 50° C.). The residue is taken up in 15 cm3 of ethyl acetate and 15 cm3 of distilled water. The organic phase is dried over magnesium sulphate, filtered through a sinter funnel and then evaporated under reduced pressure (2 kPa; 50° C.). The residue is taken up in 15 cm3 of dichloromethane, filtered and dried under reduced pressure (90 Pa; 50° C.) to give 390 mg of N-[5-(trifluoromethyl)-1H-indazol-3-yl]butanamide in the form of an off-white solid melting at 230° C.
Reaction SMILES: [NH2:1][CH2:2][C:3]([NH:5][CH2:6][C:7]([OH:9])=[O:8])=[O:4].ClC(Cl)(Cl)[C:12]([C:14]([F:17])([F:16])[F:15])=[O:13]>CS(C)=O>[F:15][C:14]([F:17])([F:16])[C:12]([NH:1][CH2:2][C:3]([NH:5][CH2:6][C:7]([OH:9])=[O:8])=[O:4])=[O:13]
Reactant: NCC(=O)NCC(=O)O
Reactant: O=C(C(F)(F)F)C(Cl)(Cl)Cl
Solvent: CS(C)=O
Product: O=C(O)CNC(=O)CNC(=O)C(F)(F)F
Temperature: 25 °C
Reaction time: 24 h
Yield: 42.5 %

Procedure:
A mixture of 7.85 mmol of glycylglycine, 15 ml of dimethyl sulfoxide and 24 mmol of sym-trichlorotrifluoroacetone was stirred at room temperature for 24 hours in a flask protected from atmospheric moisture. The reaction mixture was then poured into 50 ml of ice water and the resultant mixture was extracted thrice with n-butanol and chromatographed on a column packed with silica gel. N-trifluoroacetylglycylglycine, melting at 184.7°-185.0° C., was obtained in a yield of 42.5 percent.
Reaction SMILES: [Br:1][C:2]1[C:3]([OH:10])=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=O.Cl[CH2:12][C:13]([O:15]C)=[O:14].C(=O)([O-])[O-].[K+].[K+].[OH-].[K+]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C1COCC1.O>[Br:1][C:2]1[C:3]2[O:10][C:12]([C:13]([OH:15])=[O:14])=[CH:5][C:4]=2[CH:7]=[CH:8][CH:9]=1
Reactant: O=Cc1cccc(Br)c1O
Reactant: COC(=O)CCl
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])[O-]
Agent: [I-]
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)c1cc2cccc(Br)c2o1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
13.5 g (40.3 mmol) of 3-bromo-2-hydroxybenzaldehyde (Example 28A, 62% pure) are heated together with 9.18 g (84.62 mmol) of methyl chloroacetate, 1.49 g (4.03 mmol) of tetra-n-butylammonium iodide and 22.28 g (161.18 mmol) of potassium carbonate at 130° C. for 6 h. After cooling to RT, 100 ml of water and 100 ml of THF, and 13.57 g (241.77 mmol) of potassium hydroxide are added, and the mixture is stirred at RT overnight. The solvent is removed under reduced pressure, and the residue is taken up in 400 ml of water and washed four times with a total of 400 ml of diethyl ether. While cooling in ice, the pH is adjusted to 0 with concentrated hydrochloric acid and five extractions with a total of 700 ml of ethyl acetate are carried out. The organic phase is washed with 100 ml of saturated sodium chloride solution and then dried over magnesium sulphate. The crude product is completely freed of residual solvents under high vacuum and is stirred with 80 ml of diethyl ether. The product is filtered off and washed with a little ice-cold diethyl ether. 4.8 g (47% of theory) of the title compound are isolated.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[CH:19][C:18]([C:21]4[CH:22]=[C:23]([CH:27]=[CH:28][C:29]=4[CH3:30])[C:24](O)=[O:25])=[CH:17][C:11]=3[C:12]=2[C:13](=[O:16])[NH:14][CH3:15])=[CH:4][CH:3]=1.[CH3:31][C:32]1[O:36][CH:35]=[N:34][C:33]=1[C:37]1([NH2:40])[CH2:39][CH2:38]1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>ClCCl.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[O:9][C:10]3[CH:20]=[CH:19][C:18]([C:21]4[CH:22]=[C:23]([C:24](=[O:25])[NH:40][C:37]5([C:33]6[N:34]=[CH:35][O:36][C:32]=6[CH3:31])[CH2:39][CH2:38]5)[CH:27]=[CH:28][C:29]=4[CH3:30])=[CH:17][C:11]=3[C:12]=2[C:13]([NH:14][CH3:15])=[O:16])=[CH:6][CH:7]=1
Reactant: CNC(=O)c1c(-c2ccc(F)cc2)oc2ccc(-c3cc(C(=O)O)ccc3C)cc12
Reactant: Cc1ocnc1C1(N)CC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: ClCCl
Product: CNC(=O)c1c(-c2ccc(F)cc2)oc2ccc(-c3cc(C(=O)NC4(c5ncoc5C)CC4)ccc3C)cc12
Temperature: 25 °C
Reaction time: 18 h

Procedure:
3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methylbenzoic acid (0.2 g, 0.5 mmol, 1 eq), 1-(5-methyloxazol-4-yl)cyclopropanamine (0.103 g, 0.74 mmol, 1.2 eq), EDCI.HCl (0.105 g, 0.54 mmol, 1.1 eq), HOBT (0.067 g, 0.5 mmol, 1.0 eq) and TEA (0.21 ml, 1.5 mmol, 3 eq) were dissolved in dichloromethane and the above mixture was stirred at room temperature for 18 h. The mixture was then added with water. The organic layer was separated, washed with water and concentrated to give the crude product which was purified by Prep. TLC (20 mm thickness) using 5% methanol/DCM as an eluent. Yield: 25 mg (25%) 1HNMR (400 MHz, DMSO-d6): δ 1.11 (m, 2H), 1.20-1.22 (m, 2H), 2.28 (s, 3H), 2.29 (s, 3H), 2.82 (d, J=4.4 Hz, 3H), 7.38-7.42 (m, 4H), 7.57 (s, 1H), 7.74-7.81 (m, 3H), 8.04 (s, 1H), 7.97-8.01 (m, 2H), 8.45-8.46 (m, 1H), 9.16 (s, 1H). LCMS: (ES+) m/z=524.2 (M+H)+
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([C:13]([CH3:16])([CH3:15])[CH3:14])=[N:10][C:9]=2[C:17]2[C:18]([F:35])=[C:19]([NH:23][S:24]([C:27]3[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:28]=3[F:34])(=[O:26])=[O:25])[CH:20]=[CH:21][CH:22]=2)[CH:5]=[CH:4][N:3]=1.[CH2:36]([NH2:40])[CH:37]([CH3:39])[CH3:38]>>[CH3:14][C:13]([C:11]1[S:12][C:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:40][CH2:36][CH:37]([CH3:39])[CH3:38])[N:7]=2)=[C:9]([C:17]2[C:18]([F:35])=[C:19]([NH:23][S:24]([C:27]3[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:28]=3[F:34])(=[O:26])=[O:25])[CH:20]=[CH:21][CH:22]=2)[N:10]=1)([CH3:16])[CH3:15]
Reactant: CC(C)CN
Reactant: CC(C)(C)c1nc(-c2cccc(NS(=O)(=O)c3cc(F)ccc3F)c2F)c(-c2ccnc(Cl)n2)s1
Product: CC(C)CNc1nccc(-c2sc(C(C)(C)C)nc2-c2cccc(NS(=O)(=O)c3cc(F)ccc3F)c2F)n1

Procedure:
Following a procedure analogous to the procedure described in Example 18, Step B using N-{3-[5-(2-chloro-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,5-difluorobenzenesulfonamide (100 mg, 0.186 mmol) and isobutylamine (2 mL) the title compound was obtained as a white powder (52 mg, 48.7% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.76 (s, 1H), 8.04 (d, J=5.2 Hz, 1H), 7.35-7.57 (m, 6H), 7.28 (t, J=7.8 Hz, 1H), 5.84 (bs, 1H), 2.95 (bs, 2H), 1.80 (bs, 1H), 1.40 (s, 9H), 0.86 (d, J=5.5 Hz, 6H). MS (ESI): 574 [M−H]−.
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([F:8])[C:5]([C:9]([N:11]2[CH2:15][CH2:14][CH2:13][C@H:12]2[CH2:16][N:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)=[O:10])=[C:4]([F:22])[CH:3]=1.[N:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1>>[F:8][C:6]1[CH:7]=[C:2]([C:26]2[CH:27]=[CH:28][N:23]=[CH:24][CH:25]=2)[CH:3]=[C:4]([F:22])[C:5]=1[C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[CH2:16][N:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1)=[O:10]
Reactant: O=C(c1c(F)cc(Br)cc1F)N1CCC[C@H]1CN1CCCC1
Reactant: OB(O)c1ccncc1
Product: O=C(c1c(F)cc(-c2ccncc2)cc1F)N1CCC[C@H]1CN1CCCC1

Procedure:
The title compound is prepared in a manner substantially analogous to Example 14 via Procedure F′ from (4-bromo-2,6-difluoro-phenyl)-(2-(S)-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone and pyridine-4-boronic acid. MS (FIA) 372 (MH+)
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9](=[O:16])[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12].C[O-].[Na+].Br[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32].[I-].[K+]>C(O)C>[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([CH:10]([CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH3:21])[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[O:16]
Reactant: CCCCCCCCCCCCBr
Reactant: CCOC(=O)CC(=O)Cc1ccccc1C
Agent: C[O-]
Agent: [I-]
Agent: [K+]
Solvent: CCO
Product: CCCCCCCCCCCCC(C(=O)Cc1ccccc1C)C(=O)OCC
Temperature: 25 °C
Reaction time: 18 h

Procedure:
Three parts of ethyl 4-(2-methylphenyl)-3-oxobutanoate, 1 part of sodium methoxide, 4.6 parts of 1-bromododecane, 0.5 parts of potassium iodide and 50 parts of absolute ethanol were refluxed together for 4 hours and then stirred 18 hours at room temperature. The mixture was evaporated to a small volume, diluted with 100 parts water and extracted with ether. The ether extract was washed with saturated sodium bicarbonate, saturated sodium chloride solution and dried over magnesium sulfate. Evaporation of the ether gave 6 parts of crude ethyl 2-[(2-methylphenyl)acetyl]tetradecanoate as an oil which was not further purified.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8]([C:10]2[C:14]3[CH:15]=[N:16][CH:17]=[C:18]([F:19])[C:13]=3[N:12]([C:20]([CH3:31])([CH3:30])[CH2:21][O:22][Si:23]([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24])[CH:11]=2)=[O:9])[CH:5]=[N:6][CH:7]=1.[Cl:32][C:33]1[CH:34]=[CH:35][C:36]([CH2:39][C:40](O)=[O:41])=[N:37][CH:38]=1.CCN(C(C)C)C(C)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>C1COCC1>[C:26]([Si:23]([CH3:24])([CH3:25])[O:22][CH2:21][C:20]([N:12]1[C:13]2[C:18]([F:19])=[CH:17][N:16]=[CH:15][C:14]=2[C:10]([C:8]([C:4]2[CH:3]=[C:2]([NH:1][C:40](=[O:41])[CH2:39][C:36]3[CH:35]=[CH:34][C:33]([Cl:32])=[CH:38][N:37]=3)[CH:7]=[N:6][CH:5]=2)=[O:9])=[CH:11]1)([CH3:31])[CH3:30])([CH3:29])([CH3:28])[CH3:27]
Reactant: O=C(O)Cc1ccc(Cl)cn1
Reactant: CC(C)(CO[Si](C)(C)C(C)(C)C)n1cc(C(=O)c2cncc(N)c2)c2cncc(F)c21
Agent: CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: CC(C)(CO[Si](C)(C)C(C)(C)C)n1cc(C(=O)c2cncc(NC(=O)Cc3ccc(Cl)cn3)c2)c2cncc(F)c21
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a solution of (5-amino-pyridin-3-yl)-{1-[2-(tert-butyl-dimethyl-silanyloxy)-1,1-dimethyl-ethyl]-7-fluoro-1H-pyrrolo[3,2-c]pyridin-3-yl}-methanone (Preparation 29, 35 mg, 79.1 μmol), (5-chloro-pyridin-2-yl)-acetic acid (18.8 mg, 106.9 μmol) and DIPEA (48 μL, 276.8 μmol) in THF (3 mL), T3P (0.16 μL, 276.8 μmol) was added and the mixture stirred at 25° C. for 18 hours. The reaction was evaporated under reduced pressure, the residue partitioned between water and ethyl acetate, the organic extracts washed with saturated sodium bicarbonate solution, dried over sodium sulphate, evaporated in vacuo and triturated with pentane-ether to afford the title compound as an off white solid (64%, 30 mg).
Reaction SMILES: O=[C:2]([CH3:20])[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([CH:11]([C:16]([O:18][CH3:19])=[O:17])[C:12]([O:14][CH3:15])=[O:13])=[CH:7][CH:6]=1.[NH2:21][CH2:22][CH:23]([C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([Cl:31])[CH:26]=1)[OH:24].C1C=CC=CC=1.C([BH3-])#N.[Na+]>CO>[CH3:19][O:18][C:16]([CH:11]([C:12]([O:14][CH3:15])=[O:13])[C:8]1[CH:7]=[CH:6][C:5]([O:4][CH2:3][CH:2]([NH:21][CH2:22][CH:23]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([Cl:31])[CH:26]=2)[OH:24])[CH3:20])=[CH:10][CH:9]=1)=[O:17]
Reactant: COC(=O)C(C(=O)OC)c1ccc(OCC(C)=O)cc1
Reactant: NCC(O)c1cccc(Cl)c1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: c1ccccc1
Product: COC(=O)C(C(=O)OC)c1ccc(OCC(C)NCC(O)c2cccc(Cl)c2)cc1
Yield: 61.2 %

Procedure:
Following a procedure similar to that described in Example 6, but using 0.42 g of dimethyl 4-(2-oxopropoxy)phenylmalonate (prepared as described in Preparation 38), 0.26 g of 2-amino-1-(3-chlorophenyl)ethanol (prepared as described in Preparation 8), 50 ml of dry benzene, 50 ml of absolute methanol and 0.9 g of sodium cyanoborohydride, and then purifying the reaction product by column chromatography through silica gel, using ethyl acetate as the eluent, 0.4 g of the title compound was obtained, having an Rf=0.28 (thin layer chromatography over silica gel, using ethyl acetate as the developing solvent).
Reaction SMILES: [S:1](Cl)(=[O:4])(=[O:3])[NH2:2].[CH2:6]([O:13][CH2:14][CH2:15][OH:16])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>>[CH2:6]([O:13][CH2:14][CH2:15][O:16][S:1](=[O:4])(=[O:3])[NH2:2])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: NS(=O)(=O)Cl
Reactant: OCCOCc1ccccc1
Product: NS(=O)(=O)OCCOCc1ccccc1

Procedure:
The title compound was prepared by procedures of Example 33 from sulfamoyl chloride and 2-(benzyloxy)ethanol except the oil obtained was then further purified by high pressure chromatography as described in earlier examples using methylene chloride as eluting agent. Fractions containing the title compound were combined and the solvent was evaporated under reduced pressure to give title compound in 54% yield as light-yellow, viscous oil.
Reaction SMILES: [CH3:1][C:2]1[NH:6][C:5]2[CH:7]=[C:8]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[CH:9]=[C:10]([C:11]([O-:13])=[O:12])[C:4]=2[N:3]=1.[OH-].[Li+].O1[CH2:26][CH2:25][CH2:24][CH2:23]1>>[CH3:23][C:24]1[CH:4]=[C:10]([CH2:11][N:6]2[C:5]3[CH:7]=[C:8]([N:14]4[CH2:15][CH2:16][O:17][CH2:18][CH2:19]4)[CH:9]=[C:10]([C:11]([OH:13])=[O:12])[C:4]=3[N:3]=[C:2]2[CH3:1])[CH:9]=[CH:8][C:25]=1[CH3:26]
Reactant: Cc1nc2c(C(=O)[O-])cc(N3CCOCC3)cc2[nH]1
Reactant: C1CCOC1
Agent: [Li+]
Agent: [OH-]
Product: Cc1ccc(Cn2c(C)nc3c(C(=O)O)cc(N4CCOCC4)cc32)cc1C
Temperature: 50 °C
Reaction time: 2 h
Yield: 66 %

Procedure:
To a mixture of methyl 1-[3,4-dimethylphenyl)methyl]-2-methyl-6-(4-morpholinyl)-1H-benzimidazole-4-carboxylate (0.24 g, 0.61 mmol) in Tetrahydrofuran (THF) (10 mL) was added in lithium hydroxide (5.99 mL, 11.99 mmol). The reaction was stirred at 50° C. for 2 h. The reaction was cooled to room temperature. The organic solvent was removed in-vacuo. The precipitate was collected by filtration. Water (20 mL) was added in. The mixture was acidified with 1 N HCl. The resulting solid was filtered and washed with water and dried to give the product (0.16 g, 66%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.18 (s, 6H), 2.58-2.75 (s, 3H), 3.06-3.22 (m, 4H), 3.71-3.82 (m, 4H), 5.55 (s, 2H), 6.94 (m, 1H), 7.04 (s, 1H), 7.11 (d, 1H, J=7.83 Hz), 7.52 (m, 2H). MS (ES+) m/e 380.2[M+H]+
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:26])[CH2:9][CH2:10][CH2:11][C:12]([N:14]2[CH:18]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:17][O:16][C:15]2=[O:25])=[O:13])=[CH:4][CH:3]=1.[F:27][C:28]1[CH:33]=[CH:32][C:31]([N:34]=[CH:35][C:36]2[CH:43]=[CH:42][C:39]([C:40]#[N:41])=[CH:38][CH:37]=2)=[CH:30][CH:29]=1.C(N(C(C)C)CC)(C)C.C[Si](Cl)(C)C.C(O)(=O)C(C(C(O)=O)O)O.C(=O)(O)[O-].[Na+]>ClCCl.[Ti](Cl)(Cl)(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:26])[CH2:9][CH2:10][CH:11]([C:12]([N:14]2[CH:18]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH2:17][O:16][C:15]2=[O:25])=[O:13])[CH:35]([C:36]2[CH:43]=[CH:42][C:39]([C:40]#[N:41])=[CH:38][CH:37]=2)[NH:34][C:31]2[CH:30]=[CH:29][C:28]([F:27])=[CH:33][CH:32]=2)=[CH:4][CH:3]=1
Reactant: O=C(CCCC(O)c1ccc(F)cc1)N1C(=O)OCC1c1ccccc1
Reactant: N#Cc1ccc(C=Nc2ccc(F)cc2)cc1
Agent: Cl[Ti](Cl)(Cl)Cl
Agent: C[Si](C)(C)Cl
Agent: O=C(O)C(O)C(O)C(=O)O
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: N#Cc1ccc(C(Nc2ccc(F)cc2)C(CCC(O)c2ccc(F)cc2)C(=O)N2C(=O)OCC2c2ccccc2)cc1
Temperature: -10 °C
Reaction time: 0.05 h

Procedure:
Under argon, 2.5 g of 3-[5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-oxazolidin-2-one are dissolved in 30 ml of dichloromethane, 3.9 g of 4-[(4-fluoro-phenylimino)methyl]benzonitrile are added and the mixture is cooled to −10° C. 6.4 ml of diisopropylethylamine are added to this mixture and then, over a period of 3 min, 4.05 ml of trimethylsilyl chloride such that the temperature does not exceed −5° C. At this temperature, the mixture is stirred for another hour, and it is then cooled to −25° C. 0.8 ml of titanium tetrachloride is then added slowly. The dark mixture is stirred at −25 to −30° C. overnight and then decomposed using 35 ml of 7% strength tartaric acid solution, and stirring is continued at room temperature for 1 hour. 15 ml of a 20% strength sodium bicarbonate solution are then added, and the mixture is stirred for another hour. Following phase separation, the org. phase is washed with 30 ml of water, dried over magnesium sulfate and concentrated to about 10 ml. After addition of 2 ml of bistrimethylsilylacetamide, the mixture is heated at reflux for 30 min and then concentrated under reduced pressure. The residue is crystallized with ethyl acetate/heptane. The product is filtered off with suction and dried under reduced pressure. This gives 5 of molecular weight 653.81 (C37H37F2N3O4Si); MS (ESI+): 654.3 (M+H+), 582.2 (M+H+—Si(CH3)3).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[N:19]=[CH:18][CH:17]=[CH:16][C:12]=2[C:13]([OH:15])=O)[CH:5]=[C:6]([F:9])[C:7]=1[F:8].CN(C=O)C.C(N=C=NCCCN(C)C)C.[NH2:36][C:37]1[S:38][C:39]2[CH:45]=[C:44]([N+:46]([O-:48])=[O:47])[CH:43]=[CH:42][C:40]=2[N:41]=1>>[N+:46]([C:44]1[CH:43]=[CH:42][C:40]2[N:41]=[C:37]([NH:36][C:13]([C:12]3[C:11]([NH:10][C:4]4[CH:5]=[C:6]([F:9])[C:7]([F:8])=[C:2]([F:1])[CH:3]=4)=[N:19][CH:18]=[CH:17][CH:16]=3)=[O:15])[S:38][C:39]=2[CH:45]=1)([O-:48])=[O:47]
Reactant: Nc1nc2ccc([N+](=O)[O-])cc2s1
Reactant: O=C(O)c1cccnc1Nc1cc(F)c(F)c(F)c1
Agent: CCN=C=NCCCN(C)C
Solvent: CN(C)C=O
Product: O=C(Nc1nc2ccc([N+](=O)[O-])cc2s1)c1cccnc1Nc1cc(F)c(F)c(F)c1
Temperature: 27 °C
Reaction time: 9 h

Procedure:
Compound 13 (185 mg, 1 mmol) and 3,4,5-trifluoro aniline (19, 147 mg, 1 mmol) was taken in ethylene glycol and refluxed at 150° C. for 5 h. Then the reaction mixture was cooled and extracted in ethyl acetate (4×25 mL) from the aqueous layer and concentrated in vacuo. The compound was further purified by column chromatography using 60-120 silica gel (ethyl acetate/hexane, 1:9) to obtain Ethyl 2-(3,4,5 trifluoroanilino) nicotinate (26) as pure product. Ethyl 2-(3,4,5 trifluoroanilino) nicotinate (26, 296 mg, 1 mmol) were refluxed with 2N NaOH in ethanol for 2 h. The reaction mixture was cooled and left acidified with 2N HCl white solids obtained, filtered and washed with water to give pure compound of 2-(3,4,5-trifluorophenylamino) nicotinic acid (33). To a stirred solution of 2-(3,4,5-trifluorophenylamino) nicotinic acid (33, 252 mg, 1 mmol) in dry DMF (10 mL) hydroxy benzotriazole HOBt (1.2 mmol) were added at 0° C. After 10 min 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDCI) (1.2 mmol) was added and finally 2-amino 6-nitro benzothiazole (37, 137 mg, 0.7 mmol) were added, then the resulting mixture was stirred at room temperature (27° C.) for 8-10 h and then the reaction mixture was quenched with NaHCO3 and extracted in ethyl acetate (4×25 mL) from the ice cold aqueous layer and dried over anhydrous Na2SO4. The resulting product (8) was purified by column chromatography employing EtOAc/Hexane as an eluent.
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[CH:9][NH:10]2)=[CH:6][N:5]=1.Cl[CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19]>CN(C=O)C>[Cl:3][C:4]1[N:5]=[CH:6][C:7]2[CH:8]=[CH:9][N:10]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[C:11]=2[CH:12]=1
Reactant: Clc1cc2[nH]ccc2cn1
Reactant: C[Si](C)(C)CCOCCl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: C[Si](C)(C)CCOCn1ccc2cnc(Cl)cc21
Reaction time: 1 h
Yield: 81.4 %

Procedure:
Sodium hydride (60%, 1.40 g, 35.0 mmol) was added in portions over 20 min to a solution of 6-chloro-5-aza-indole (4.45 g, 29.1 mmol) in DMF (17.2 mL) at 0° C. (ice bath). The mixture was stirred for 1 h. (2-Chloromethoxy-ethyl)-trimethyl-silane (5.83 g, 35.0 mmol) was then added over 15 min. After stirring for 1 h, the reaction was quenched with water (100 mL) and the mixture extracted with DCM (3×100 mL). The combined organic extracts were washed with brine (3×300 mL), dried over Na2SO4, filtered and concentrated. Chromatography on silica gel (gradient elution, 0-100%, EtOAc/petrol 40-60° C.), gave the title compound (6.7 g, 82%) as a yellow oil. 1H NMR (Me-d3-OD): 8.61 (1H, s), 7.63 (1H, s), 7.50 (1H, d), 6.71 (1H, d), 5.57 (2H, s), 3.53 (2H, t), 0.88 (2H, t), −0.04-0.16 (9H, m).
Reaction SMILES: [Al+3].[Cl-].[Cl-].[Cl-].[C:5]1([CH:11]2[CH2:16][CH2:15][CH:14]([C:17](=[O:19])[CH3:18])[CH2:13][CH2:12]2)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[C:20](Cl)(=[O:22])[CH3:21]>C(Cl)Cl>[C:17]([CH:14]1[CH2:15][CH2:16][CH:11]([C:5]2[CH:10]=[CH:9][C:8]([C:20](=[O:22])[CH3:21])=[CH:7][CH:6]=2)[CH2:12][CH2:13]1)(=[O:19])[CH3:18]
Reactant: CC(=O)Cl
Reactant: CC(=O)C1CCC(c2ccccc2)CC1
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: CC(=O)c1ccc(C2CCC(C(C)=O)CC2)cc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 46 %

Procedure:
To a suspension of AlCl3 (5.9 g, 54 mmol) in DCM (200 mL) at 0° C. was added 1-(4-phenylcyclohexyl)ethanone (9 g in DCM), and acetyl chloride (10.4 mL, 146 mmol) dropwise over 30 min. The mixture was stirred to rt for 15 min. and heated at 45° C. for 4 h. After being cooled to rt, the mixture was poured it into ice-HCl (1N). The organic layer was collected, and the aqueous layer was extracted with ethyl acetate (3×). The combined organic layers were combined, concentrated and purified on column (hexane:ethyl acetate, 8:2) to give 1-(4-(4-acetylcyclohexyl)phenyl)ethanone (A2) as a mixture of two isomers (5 g, 46% yield).