Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(O)(=O)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C1COCC1.[CH2:28]([O:31][C:32]([N:34]1[C@H:38]([CH:39]([OH:48])[C:40]2[N:41]=[CH:42][N:43]3[CH:47]=[CH:46][S:45][C:44]=23)[CH2:37][C@H:36]([S:49][C:50]2[C@H:51]([CH3:74])[C@@H:52]3[C@@H:62]([C@H:63]([O:65][Si](C(C)(C)C)(C)C)[CH3:64])[C:61](=[O:73])[N:53]3[C:54]=2[C:55]([O:57][CH2:58][CH:59]=[CH2:60])=[O:56])[CH2:35]1)=[O:33])[CH:29]=[CH2:30]>C1COCC1.C(OCC)(=O)C>[CH2:28]([O:31][C:32]([N:34]1[C@H:38]([CH:39]([OH:48])[C:40]2[N:41]=[CH:42][N:43]3[CH:47]=[CH:46][S:45][C:44]=23)[CH2:37][C@H:36]([S:49][C:50]2[C@H:51]([CH3:74])[C@@H:52]3[C@@H:62]([C@H:63]([OH:65])[CH3:64])[C:61](=[O:73])[N:53]3[C:54]=2[C:55]([O:57][CH2:58][CH:59]=[CH2:60])=[O:56])[CH2:35]1)=[O:33])[CH:29]=[CH2:30]
Reactant: C=CCOC(=O)C1=C(S[C@H]2C[C@@H](C(O)c3ncn4ccsc34)N(C(=O)OCC=C)C2)[C@H](C)[C@@H]2[C@@H]([C@@H](C)O[Si](C)(C)C(C)(C)C)C(=O)N12
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: C=CCOC(=O)C1=C(S[C@H]2C[C@@H](C(O)c3ncn4ccsc34)N(C(=O)OCC=C)C2)[C@H](C)[C@@H]2[C@@H]([C@@H](C)O)C(=O)N12
Temperature: 25 °C
Reaction time: 16 h
Yield: 85.8 %

Procedure:
Acetic acid (0.60 ml) and 3.5 ml of a 1 M tetra-n-butylammonium fluoride/THF solution are added to a solution of 491 mg of allyl(1R,5S,6S)-2-[(3S,5S)-1-allyloxycarbonyl-5-[1-hydroxy-1-(imidazo[5,1-b]thiazol-7-yl)methyl]pyrrolidin-3-yl]thio-6-[(1R)-1-(t-butyldimethylsilyloxy)ethyl]-1-methylcarbapen-2-em-3-carboxylate (a diastereomer mixture) in 10.5 ml of anhydrous THF, and the mixture is stirred in an argon atmosphere at room temperature for 16 hr. The reaction solution is diluted with 100 ml of ethyl acetate, and the diluted solution is successively washed with a 5% aqueous sodium hydrogencarbonate solution and saturated saline and dried over anhydrous magnesium sulfate, followed by filtration and the removal of the solvent by evaporation to give a dark yellow oil. This oil is purified by column chromatography on silica gel (ethyl acetate:methanol=95:5) to give 353 mg of allyl(1R,5S,6S)-2-[(3S,5S)-1-allyloxycarbonyl-5-[1-hydroxy-1-(imidazo[5,1-b]thiazol-7-yl)methyl]pyrrolidin-3-yl]thio-6-((1R)-1-hydroxyethyl)-1-methylcarbapen-2-em-3-carboxylate (a diastereomer mixture) as a light yellow amorphous material.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][NH:6][S:7]([C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:12][CH:11]=1)(=[O:9])=[O:8].[C:22](OC(=O)C)(=[O:24])[CH3:23]>N1C=CC=CC=1.ClCCl>[C:13]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:14]=[CH:15][C:10]([S:7]([NH:6][CH2:5][CH2:4][CH2:3][CH2:2][NH:1][C:22](=[O:24])[CH3:23])(=[O:9])=[O:8])=[CH:11][CH:12]=1
Reactant: NCCCCNS(=O)(=O)c1ccc(-c2ccccc2)cc1
Reactant: CC(=O)OC(C)=O
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(=O)NCCCCNS(=O)(=O)c1ccc(-c2ccccc2)cc1
Temperature: 80 °C
Reaction time: 4 h

Procedure:
Biphenyl-4-sulfonic acid (4-amino-butyl)amide (1 g) was suspended in a mixture of acetic anhydride (45 mL) and pyridine (15 mL) and stirred at 80° C. for 4 hours. The solution was left to stir overnight and then poured into ice water. The aqueous mixture was extracted with dichloromethane, dried (Na2SO4) and evaporated to give a brown oil. The oil was redissolved in dichloromethane and the title compound precipitated as a white solid by addition of a small amount of petrol. δC (CDCl3, 62.9 MHz): 23.2, 26.6, 26.8, 39.1, 42.9, 127.3, 127.6, 127.8, 128.5, 129.1, 138.4, 139.3, 145.6 and 170.9.
Reaction SMILES: [OH:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1I.[CH3:13][Si:14]([C:17]#[CH:18])([CH3:16])[CH3:15]>C1COCC1.C(Cl)(Cl)Cl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[OH:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[C:18]#[C:17][Si:14]([CH3:16])([CH3:15])[CH3:13]
Reactant: COC(=O)c1ccc(O)c(I)c1
Reactant: C#C[Si](C)(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: C1CCOC1
Solvent: ClC(Cl)Cl
Product: COC(=O)c1ccc(O)c(C#C[Si](C)(C)C)c1
Temperature: 50 °C
Yield: 50.3 %

Procedure:
Methyl 4-hydroxy-3-iodobenzoate (5.56 g, 20 mmol) is combined with trimethylsilylacetylene (3.96 mL, 28 mmol), bis(triphenylphosphine)palladium dichloride (414 mg, 0.6 mmol) and cuprous iodide (57 mg, 0.3 mmol) in THF (20 mL)/CHCl3 (40 mL) in a dry flask, under nitrogen. TEA (8.7 mL, 62.3 mmol) is added and the mixture heated to 50° C. for 4 h. The mixture is diluted with CHCl3 (60 mL), washed with 5% HCl (2×40 mL), dried (MgSO4) and concentrated to a brown solid. The crude material is adsorbed onto silica gel and chromatographed over 200 g silica gel, eluting with 15% EtOAc/hexane (2 L) followed by 20% EtOAc/hexane (1 L). Fractions are combined and concentrated to afford 2.50 g (50%) of methyl 4-hydroxy-3-[(trimethylsilyl)ethynyl]benzoate as a yellow solid. HRMS (FAB) calcd for C13H16O3SI+H: 249.0947, found 249.0955 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1([CH2:9][C:10]#[CH:11])[CH2:6][CH2:5][N:4]([CH3:7])[C:3]1=[O:8].I[C:13]1[N:18]=[C:17]([CH3:19])[CH:16]=[C:15]([C:20]2[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=2)[N:14]=1.C(NC(C)C)(C)C>COC(C)(C)C.[Cu](I)I.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:1][C:2]1([CH2:9][C:10]#[C:11][C:13]2[N:18]=[C:17]([CH3:19])[CH:16]=[C:15]([C:20]3[CH:21]=[CH:22][C:23]([C:26]([F:29])([F:27])[F:28])=[CH:24][CH:25]=3)[N:14]=2)[CH2:6][CH2:5][N:4]([CH3:7])[C:3]1=[O:8]
Reactant: C#CCC1(N)CCN(C)C1=O
Reactant: Cc1cc(-c2ccc(C(F)(F)F)cc2)nc(I)n1
Agent: I[Cu]I
Agent: c1ccc([P]([Pd][P](c2ccccc2)(c2ccccc2)c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: COC(C)(C)C
Solvent: CC(C)NC(C)C
Product: Cc1cc(-c2ccc(C(F)(F)F)cc2)nc(C#CCC2(N)CCN(C)C2=O)n1
Temperature: 25 °C
Reaction time: 120 h
Yield: 80.3 %

Procedure:
To a stirred solution of 3-amino-1-methyl-3-prop-2-ynyl-pyrrolidin-2-one (which may be prepared as described in Description 3) (2.3 g, 15.11 mmol) in tert-butyl methyl ether (50 mL) was added 2-iodo-4-methyl-6-[4-(trifluoromethyl)-phenyl]pyrimidine (which may be prepared as described in Description 6) (6.05 g, 16.62 mmol). diisopropylamine (6.35 mL, 45.34 mmol) was then added, followed by copper iodide (57.56 mg, 0.300 mmol) and bis(triphenylphosphine)palladium (II) dichloride (106.07 mg, 0.1500 mmol). The reaction was then stirred at room temperature for 5 days. The reaction mixture was transferred to a separating funnel and the flask washed with an additional quantity of tert-butyl methyl ether (15 ml). The organic solution was washed with water (2×50 mL) and brine (50 mL). The organic phase was dried over magnesium sulphate, filtered, and then the magnesium sulphate washed with dichloromethane (30 ml). The filtrate was concentrated at reduced pressure to give a yellow foam. The product was purified by silica gel chromatography eluting with ethyl acetate followed by an increasing percentage of a solution of 10% 0.880 ammonia in methanol, to give the title compound (D8a) as a yellow foam (4.71 g). This racemate was consistent by NMR and mass spectroscopy with the S isomer prepared in Description 8.
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7][C:8](Cl)=[N:9]2)([O-])=O.[Cl:15][C:16]1[S:20][C:19]([S:21](Cl)(=[O:23])=[O:22])=[CH:18][CH:17]=1.[CH3:25][O:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[CH:33]([NH2:35])[CH3:34]>>[CH3:25][O:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[CH:33]([NH:35][C:8]1[CH:7]=[CH:6][C:5]2[C:10](=[CH:11][CH:12]=[CH:13][C:4]=2[NH:1][S:21]([C:19]2[S:20][C:16]([Cl:15])=[CH:17][CH:18]=2)(=[O:23])=[O:22])[N:9]=1)[CH3:34]
Reactant: O=S(=O)(Cl)c1ccc(Cl)s1
Reactant: COc1ccccc1C(C)N
Reactant: O=[N+]([O-])c1cccc2nc(Cl)ccc12
Product: COc1ccccc1C(C)Nc1ccc2c(NS(=O)(=O)c3ccc(Cl)s3)cccc2n1

Procedure:
The title compound, MS: m/e=474.1 (M+H+), was prepared in accordance with the general method of example 61 from 5-nitro-2-chloroquinoline, 5-chlorothiophene-2-sulfonylchloride and rac-1-(2-methoxy-phenyl)-ethylamine.
Reaction SMILES: Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[C:7]2[CH2:12][CH2:13][CH2:14][O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17].[CH3:23][N:24](C)C=O>C(OCC)(=O)C.[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:20][C:19]([Si:16]([CH3:18])([CH3:17])[O:15][CH2:14][CH2:13][CH2:12][C:7]1[C:8]2[CH:9]=[CH:10][CH:11]=[C:2]([C:23]#[N:24])[C:3]=2[CH:4]=[CH:5][N:6]=1)([CH3:22])[CH3:21]
Reactant: CN(C)C=O
Reactant: CC(C)(C)[Si](C)(C)OCCCc1nccc2c(Br)cccc12
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [C-]#N
Agent: [Zn+2]
Solvent: CCOC(C)=O
Product: CC(C)(C)[Si](C)(C)OCCCc1nccc2c(C#N)cccc12

Procedure:
A microwave vial was charged with 5-bromo-1-(3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)isoquinoline (D11; 640 mg, 1.68 mmol), dry, degassed N,N-dimethylformamide (DMF) (8 ml), zinc cyanide (217 mg, 1.85 mmol) and tetrakis(triphenylphosphine)palladium(0) (194 mg, 0.168 mmol). The reaction vessel was sealed and heated using microwave irradiation to 120° C. for 60 min. After cooling, the mixture was diluted with ethyl acetate, the organic layers partitioned with water (×3) and the aqueous layer discarded. The organic layers were passed through a hydrophobic frit before being concentrated in vacuo. The resultant yellow oil was purified by flash column chromatography on silica using 2% to 20% ethyl acetate in cyclohexane as eluent. The relevant fractions were pooled and concentrated in vacuo to give the title compound as a yellow oil (417 mg).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([OH:11])[C:5](=[CH:9][CH:10]=1)[C:6]([OH:8])=[O:7].[NH2:12][C:13]1[CH:21]=[C:17]([C:18]([OH:20])=[O:19])[C:16]([OH:22])=[CH:15][CH:14]=1.[C:23]1([O:29][C:30](Cl)=[O:31])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(=O)([O-])O.[Na+]>>[C:23]1([O:29][C:30]([NH:1][C:2]2[CH:3]=[C:4]([OH:11])[C:5](=[CH:9][CH:10]=2)[C:6]([OH:8])=[O:7])=[O:31])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[C:23]1([O:29][C:30]([NH:12][C:13]2[CH:21]=[C:17]([C:18]([OH:20])=[O:19])[C:16]([OH:22])=[CH:15][CH:14]=2)=[O:31])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: Nc1ccc(C(=O)O)c(O)c1
Reactant: Nc1ccc(O)c(C(=O)O)c1
Reactant: O=C(Cl)Oc1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Product: O=C(Nc1ccc(C(=O)O)c(O)c1)Oc1ccccc1
Product: O=C(Nc1ccc(O)c(C(=O)O)c1)Oc1ccccc1

Procedure:
In the preparation process described in J. Pharm. Sci., 52, 927 (1963), 4-aminosalicylic acid and 5-aminosalicylic acid is reacted with phenylchloroformate in an aqueous sodium hydrogen carbonate solution to obtain 4-phenyloxycarbonylaminosalicylic acid and 5-phenyloxycarbonylaminosalicylic acid, respectively, in the relatively high yield.
Reaction SMILES: I[C:2]1[CH:3]=[N:4][NH:5][CH:6]=1.[CH3:7][Si:8]([C:11]#[CH:12])([CH3:10])[CH3:9].C(NCC)C>C1COCC1.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cu](I)I>[CH3:7][Si:8]([C:11]#[C:12][C:2]1[CH:3]=[N:4][NH:5][CH:6]=1)([CH3:10])[CH3:9]
Reactant: C#C[Si](C)(C)C
Reactant: Ic1cn[nH]c1
Agent: Cl[Pd]Cl
Agent: I[Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCNCC
Solvent: C1CCOC1
Product: C[Si](C)(C)C#Cc1cn[nH]c1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
4-Iodo-1H-pyrazole (20.0 g, 103 mmol) is dissolved in anhydrous THF (150 ml) and trimethylsilyl acetylene (72.8 ml, 515 mmol) is added under an inert atmosphere. Diethyl-amine (150 ml), bis-(triphenylphosphine) palladium (II) chloride (10.8 g, 15 mmol) and copper iodide (2.9 g, 15 mmol) are added and the reaction mixture is left to stir at room temperature for 3 hours. The solvent is removed under reduced pressure. The residue is dissolved in diethyl ether and the insoluble impurities are filtered off. The solvent is removed under reduced pressure. The residue is dissolved in methanol and the insoluble impurities removed. The solvent is removed under reduced pressure. The residue is purified by dry flash chromatography on silica gel eluting with a gradient system of diethyl ether: iso-hexane (20:80 to 100:0) to afford the title compound [MH+] 165.07 1H NMR (DMSO): 0.00 (s, 9H), 7.45 (s, 1H), 7.90 (s, 1H), 12.90 (br s, 1H)
Reaction SMILES: [CH:1]1([CH2:4][CH2:5][C:6]2([CH3:19])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9](=[O:16])[CH:8]=[C:7]2[O:17]C)[CH2:3][CH2:2]1.[OH-].[Na+].Cl>O1CCOCC1.O>[CH:1]1([CH2:4][CH2:5][C:6]2([CH3:19])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]([OH:16])=[CH:8][C:7]2=[O:17])[CH2:3][CH2:2]1
Reactant: COC1=CC(=O)c2ccccc2C1(C)CCC1CC1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: O
Product: CC1(CCC2CC2)C(=O)C=C(O)c2ccccc21
Temperature: 95 °C
Yield: 63.9 %

Procedure:
To a solution of Example 157C (1.06 g, 4.10 mmol) in dioxane (10 mL) was added 1 N NaOH (10 mL, 10 mmol) and the reaction mixture heated at 95° C. for 16 hours. After cooling the solution to room temperature, the reaction mixture was diluted with 50 mL of water, the pH adjusted to 2.0 with 1N HCl, and the aqueous layer extracted 3 times with ethyl acetate. The combined organic layers were washed with brine and dried over MgSO4. The product was purified by flash chromatography on SiO2 eluting with a 10-25% ethyl acetate/hexane gradient yielding the title compound (0.635 g, 64% yield) as a crystalline solid. 1H NMR (300 MHz, DMSO-d6): δ ppm−0.51 (m, 2H) −0.02 (m, 2H) 0.14 (m, 2H) 0.46 (m, 1H) 1.16 (s, 3H) 5.42 (s, 1H) 7.12 (t, J=7.35 Hz, 1H) 7.34 (m, 2H) 7.64 (d, J=7.35 Hz, 1H). MS (ESI+) m/z=243 (M+H)+.
Reaction SMILES: CS([C:4]1[N:9]=[CH:8][C:7]2=[CH:10][CH:11]=[C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[O:19][CH3:20])[N:6]2[N:5]=1)=O.[NH2:21][C:22]1[CH:23]=[C:24]2[C:35](=[CH:36][C:37]=1[O:38][CH3:39])[O:34][C:27]1([CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]1)[CH:26]=[CH:25]2.C(N(CC)C(C)C)(C)C.COCC(O)C>>[CH3:39][O:38][C:37]1[CH:36]=[C:35]2[C:24]([CH:25]=[CH:26][C:27]3([O:34]2)[CH2:28][CH2:29][N:30]([CH3:33])[CH2:31][CH2:32]3)=[CH:23][C:22]=1[NH:21][C:4]1[N:9]=[CH:8][C:7]2=[CH:10][CH:11]=[C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[O:19][CH3:20])[N:6]2[N:5]=1
Reactant: COc1ccccc1-c1ccc2cnc(S(C)=O)nn12
Reactant: COc1cc2c(cc1N)C=CC1(CCN(C)CC1)O2
Solvent: CCN(C(C)C)C(C)C
Solvent: COCC(C)O
Product: COc1cc2c(cc1Nc1ncc3ccc(-c4ccccc4OC)n3n1)C=CC1(CCN(C)CC1)O2
Yield: 9.9 %

Procedure:
A slurry of 2-Methanesulfinyl-7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazine (78.0 mg, 0.271 mmol), 6-Amino-7-methoxy-1′-methyl-spiro[chromene-2,4′-piperidin]-4-((3H)-one (151 mg, 0.546 mmol)) and N,N-Diisopropylethylamine (0.150 mL, 0.861 mmol) in 1-Methoxy-2-propanol (0.300 mL, 3.07 mmol) was irradiated in a CEM microwave (200° C., 60 min). Purification by prep HPLC afforded 7-methoxy-6-{[7-(2-methoxyphenyl)pyrrolo[2,1-f][1,2,4]triazin-2-yl]amino}-1′-methylspiro[chromene-2,4′-piperidin]-4-((3H)-one trifluoroacetic acid salt (13 mg; Yield=7.8%). 1H-NMR (DMSO-d6): 9.41 (br s, 1H), 8.93 (s, 1H), 8.16 (s, 1H), 7.82 (m, 2H), 7.39 (m, 1H), 7.18 (d, 1H, J=8.3 Hz), 7.07 (m, 1H), 6.99 (d, 1H, J=4.2 Hz), 6.94 (d, 1H, J=4.2 Hz), 6.79 (s, 1H), 3.93 (s, 3H), 3.79 (s, 3H), 3.34 (m, 2H), 3.20 (m, 2H), 2.84 (s, 3H), 2.82 (s, 2H), 2.17 (m, 2H), 1.87 (m, 2H). LCMS (HPLC): m/z=550 (M+H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH:16]=[CH:17][C:18]2[CH:19]=[C:20]3[C:25](=[CH:26][CH:27]=2)[NH:24][C:23](=[O:28])[CH2:22][CH2:21]3)[CH2:10][CH2:9]1.Cl.[H][H]>O.[C].[Pd]>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[CH2:9][CH2:10][N:11]([CH2:14][CH2:15][CH2:16][CH2:17][C:18]2[CH:19]=[C:20]3[C:25](=[CH:26][CH:27]=2)[NH:24][C:23](=[O:28])[CH2:22][CH2:21]3)[CH2:12][CH2:13]1
Reactant: O=C1CCc2cc(C=CCCN3CCN(c4ccccc4Cl)CC3)ccc2N1
Reactant: [H][H]
Agent: [Pd]
Agent: Cl
Solvent: O
Product: O=C1CCc2cc(CCCCN3CCN(c4ccccc4Cl)CC3)ccc2N1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
0.37 Gram of 6-{4-[4-(2-chlorophenyl)-1-piperazinyl]-1-butenyl}-3,4-dihydrocarbostyril and 0.1 g of 10%-palladium carbon were suspended in 40 ml of water, then 0.2 ml of concentrated hydrochloric acid was added to the suspension and the mixture was catalytically hydrogenated under 5 atmospheric pressure of hydrogen gas at an ordinary temperature. The catalyst was removed by filtration and to the filtrate were added 10N-NaOH and ether and stirred at a room temperature for 30 minutes. The crystals thus precipitated were collected by filtration and recrystallized from ispropanol to obtain 6-{4-[4-(2-chlorophenyl)-1-piperazinyl]butyl}-3,4-dihydrocarbostyril in colorless prism-like crystals. Yield: 0.27 g. Melting point: 129°-130° C.
Reaction SMILES: FC1C=CC(S(CCC)(=O)=O)=CC=1C#C[Si](C)(C)C.[C:20]([O:24][C:25](=[O:37])[CH2:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][C:29]=1[C:35]#[CH:36])([CH3:23])([CH3:22])[CH3:21].Br[C:39]1[CH:40]=[C:41]([S:46]([N:49]([CH3:51])[CH3:50])(=[O:48])=[O:47])[CH:42]=[CH:43][C:44]=1[F:45]>>[C:20]([O:24][C:25](=[O:37])[CH2:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][C:29]=1[C:35]#[C:36][C:39]1[CH:40]=[C:41]([S:46]([N:49]([CH3:50])[CH3:51])(=[O:47])=[O:48])[CH:42]=[CH:43][C:44]=1[F:45])([CH3:23])([CH3:22])[CH3:21]
Reactant: C#Cc1cc(Cl)ccc1OCC(=O)OC(C)(C)C
Reactant: CN(C)S(=O)(=O)c1ccc(F)c(Br)c1
Agent: CCCS(=O)(=O)c1ccc(F)c(C#C[Si](C)(C)C)c1
Product: CN(C)S(=O)(=O)c1ccc(F)c(C#Cc2cc(Cl)ccc2OCC(=O)OC(C)(C)C)c1

Procedure:
Following the general method as outlined in Intermediate 107, starting from (4-chloro-2-ethynyl-phenoxy)-acetic acid tert-butyl ester (Intermediate 3) and 3-bromo-4-fluoro-N,N-dimethylbenzenesulfonamide (Intermediate 138), the title compound was obtained as a colorless oil after purification by flash column chromatography (silica), eluting with cyclohexane containing increasing amounts of EtOAc.
Reaction SMILES: [C:1]1(=[O:8])[NH:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(C(C)C)CC)(C)C.[C:18](Cl)(=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>O>[C:18]([N:7]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][C:1]1=[O:8])(=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: O=C1CCCCCN1
Reactant: O=C(Cl)c1ccccc1
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Product: O=C1CCCCCN1C(=O)c1ccccc1
Temperature: 90 °C
Reaction time: 1 h
Yield: 95 %

Procedure:
Under a stream of nitrogen, 200 g of ε-caprolactam are introduced into a 1 l four-necked flask fitted with stirrer and thermometer and melted. 226 g of N,N-diisopropyl-N-ethylamine (Hunig base) and 250 g of benzoyl chloride are then added dropwise simultaneously over the course of 2 hours, with stirring. The temperature is maintained initially at 90° C.and then increased further to 110° C. When the reaction is complete, the melt, at 80° C., is introduced into 350 ml of water at room temperature and stirred. After one hour, the precipitated benzoylcaprolactam is filtered off and dried. The N-benzoylcaprolactam is obtained in a yield of 95% and a purity of >99% by GC. The Hunig base is worked up as in Example 1. The precipitated N,N-diisopropyl-N-ethylamine (water content: 0.13%) can again be reused without further purification.
Reaction SMILES: [CH2:1]([N+:5]([CH2:14][CH2:15][CH2:16][CH3:17])([CH2:10][CH2:11][CH2:12][CH3:13])[CH2:6][CH2:7][CH2:8][CH3:9])[CH2:2][CH2:3][CH3:4].[NH2:18][C:19]1([O:28][CH3:29])[CH2:22][N:21]([S:23]([O-:26])(=[O:25])=[O:24])[C:20]1=[O:27].N1C=CC=CC=1.[CH2:36]([O:43][C:44]([CH:46]([C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)[C:47](Cl)=[O:48])=[O:45])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(#N)C.C(Cl)Cl>[CH2:14]([N+:5]([CH2:1][CH2:2][CH2:3][CH3:4])([CH2:6][CH2:7][CH2:8][CH3:9])[CH2:10][CH2:11][CH2:12][CH3:13])[CH2:15][CH2:16][CH3:17].[O:48]=[C:47]([NH:18][C:19]1([O:28][CH3:29])[CH2:22][N:21]([S:23]([O-:26])(=[O:24])=[O:25])[C:20]1=[O:27])[CH:46]([C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)[C:44](=[O:45])[O:43][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1
Reactant: COC1(N)CN(S(=O)(=O)[O-])C1=O
Reactant: O=C(Cl)C(C(=O)OCc1ccccc1)c1ccccc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: c1ccncc1
Solvent: ClCCl
Solvent: CC#N
Product: COC1(NC(=O)C(C(=O)OCc2ccccc2)c2ccccc2)CN(S(=O)(=O)[O-])C1=O
Temperature: -10 °C
Reaction time: 0.25 h
Yield: 69.2 %

Procedure:
Crude 3-amino-3-methoxy-2-oxo-1-azetidinesulfonic acid, tetrabutylammonium salt (431 mg, see Example 74), containing borax, is dissolved in 30 ml of dry acetonitrile. Dry pyridine (317 μl) is added and the solution stirred well at -10° C. under dry nitrogen. α-(Benzyloxycarbonyl)phenylacetyl chloride (568 mg) in 3 ml of dry acetonitrile is added dropwise. Thin layer chromatography indicates the reaction to be complete after 15 minutes. Potassium phosphate buffer (0.5M, pH 5.5, 17 ml) is added and most of the acetonitrile is removed in vacuo. The residue is diluted with water and extracted three times with equal volumes of methylene chloride. The extract is dried over anhydrous sodium sulfate and evaporated in vacuo to give 1.032 g of crude product, which is dissolved in 3 ml of methylene chloride and chromatographed on a silica column using methylene chloride-methanol to give 470 mg of the title compound.
Reaction SMILES: Br[C:2]1[C:3]([CH3:20])=[CH:4][C:5]2[O:10][C:9]([CH3:12])([CH3:11])[N:8]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=3)[C:6]=2[CH:19]=1.[C-:21]#[N:22].[Na+]>CN(C)C=O.O>[C:21]([C:2]1[C:3]([CH3:20])=[CH:4][C:5]2[O:10][C:9]([CH3:12])([CH3:11])[N:8]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=3)[C:6]=2[CH:19]=1)#[N:22]
Reactant: [C-]#N
Reactant: Cc1cc2c(cc1Br)C(c1ccccn1)=NC(C)(C)O2
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1cc2c(cc1C#N)C(c1ccccn1)=NC(C)(C)O2
Reaction time: 0.25 h
Yield: 20.9 %

Procedure:
Cuprous cyanide (1.1 g) was added to a solution of Compound 46 (2.0 g) in dimethylformamide (5 ml) and the mixture was heated under reflux for 23 hours. The reaction mixture was air-cooled. The mixture was then added to a solution of sodium cyanide (2.2 g) in water (6.5 ml), and the mixture was stirred for 15 minutes. The mixture was extracted with ethyl acetate, successively washed with aqueous 5% sodium cyanide solution and saturated saline solution and dried over anhydrous magnesium sulfate. The solvent was distilled off. The resulting crude product was washed with ether/isopropyl ether to obtain 6-cyano-2,2,7-trimethyl-4-(2-pyridyl)-2H-1,3-benzoxazine (0.35 g) (Compound 64).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:9]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:10][CH2:11][C:12]([OH:14])=O)[CH:5]=[CH:6][C:7]=1[Cl:8].S(Cl)(Cl)=O.Cl.[Al+3].[Cl-].[Cl-].[Cl-]>C1(C)C=CC=CC=1.C(=S)=S>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]2[C:15]3[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:12](=[O:14])[CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: O=C(O)CCC(c1ccccc1)c1ccc(Cl)c(Cl)c1
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: O=S(Cl)Cl
Solvent: Cc1ccccc1
Solvent: S=C=S
Product: O=C1CCC(c2ccc(Cl)c(Cl)c2)c2ccccc21
Yield: 48 %

Procedure:
A solution of 4-(3,4-dichlorophenyl)-4-phenylbutanoic acid (228 g., 0.74 mole) in toluene (1.2 l.) was treated with thionyl chloride (66 ml., 0.90 mole) and the resulting solution heated at reflux for 75 minutes, with provision made for trapping HCl gas given off from the refluxing reaction solution. The reaction solution was then evaporated under vacuum to about 230 g. of a light brown oil. The oil was dissolved in carbon disulfide (360 ml.) and the resulting solution added to a well stirred suspension of AlCl3 (1.5 kg., 12.5 moles) in carbon disulfide (1.20 l.), with the mixture held below 8° C. during the addition period, forming a brown mass. After the addition was completed, the reaction mixture was stirred for about 16 hours at room temperature and then slowly poured on ice (vigorous reaction). The resulting suspension was extracted with ethyl acetate (2×4 l.). The combined extract was washed with water, washed with saturated aqueous sodium bicarbonate solution, dried and evaporated under vacuum to a residue, which was crystallized from hexane (500 ml.) to yield the named product (104.1 g., 48% yield, m.p. 99°-101° C., elemental analysis calculated: 66.00% C; 4.16% H; found: 66.06% C; 4.23% H).