Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:7]2[C:8](=[O:22])[N:9]3[CH2:21][CH2:20][CH2:19][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16](=[S:18])[NH2:17])[C:6]=2[CH:5]=[CH:4][CH:3]=1.[Cl:23][CH2:24][C:25](=O)[CH2:26]Cl>O1CCOCC1>[Cl:1][C:2]1[C:7]2[C:8](=[O:22])[N:9]3[CH2:21][CH2:20][CH2:19][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]3[S:18][CH:26]=[C:25]([CH2:24][Cl:23])[N:17]=3)[C:6]=2[CH:5]=[CH:4][CH:3]=1
Reactant: O=C(CCl)CCl
Reactant: NC(=S)c1ncn2c1[C@@H]1CCCN1C(=O)c1c(Cl)cccc1-2
Solvent: C1COCCO1
Product: O=C1c2c(Cl)cccc2-n2cnc(-c3nc(CCl)cs3)c2[C@@H]2CCCN12
Reaction time: 1 h
Yield: 56.8 %

Procedure:
A suspension of 6.8 g (0.0204 mol) of (S)-8-chloro-9-oxo-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]-benzodiazepine-thiocarboxamide in 100 ml of dioxan was treated with 2.85 g (0.0224 mol) of 1,3-dichloro-2-propanone and boiled at reflux for 48 hrs. After cooling 30 g of silica gel were added and the mixture was stirred for a further 1 hr. The mixture was concentrated in a water-jet vacuum and dried in a high vacuum. The crude product, adsorbed on silica gel, was applied to a silica gel column equilibrated with ethyl acetate and then eluted with ethyl acetate. There were obtained 4.7 g (58%) of (S)-8-chloro-1-(4-chloromethyl-thiazol-2-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one in the form of white crystals.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([NH2:8])[N:5]=[C:4]([NH:9][CH2:10][C:11]2[CH:16]=[C:15]([O:17][CH3:18])[CH:14]=[CH:13][C:12]=2[O:19][CH3:20])[C:3]=1[NH2:21].[N:22]([O-])=O.[Na+]>>[Cl:1][C:2]1[C:3]2[N:21]=[N:22][N:9]([CH2:10][C:11]3[CH:16]=[C:15]([O:17][CH3:18])[CH:14]=[CH:13][C:12]=3[O:19][CH3:20])[C:4]=2[N:5]=[C:6]([NH2:8])[N:7]=1
Reactant: COc1ccc(OC)c(CNc2nc(N)nc(Cl)c2N)c1
Reactant: O=N[O-]
Agent: [Na+]
Product: COc1ccc(OC)c(Cn2nnc3c(Cl)nc(N)nc32)c1

Procedure:
A solution of 6-chloro-N4-(2,5-dimethoxy-benzyl)-pyrimidine-2,4,5-triamine was treated with a cold aqueous solution of NaNO2, following the general procedure 2. HPLC RT was 6.130 min. 1HNMR (CDCl3): δ 6.84–6.83 (m, 2H), 6.64–6.63 (d, 1H), 5.67 (s, 2H), 5.54 (s, 2H), 3.83 (s, 3H), 3.73 (s, 3H).
Reaction SMILES: [CH3:1][C:2]1[N:3]2[CH:9]=[C:8]([C:10]3[CH:15]=[CH:14][C:13]([N+:16]([O-])=O)=[CH:12][CH:11]=3)[N:7]=[C:4]2[S:5][CH:6]=1.O.O.[Sn](Cl)Cl.C(Cl)Cl.CCOC(C)=O>CCO>[CH3:1][C:2]1[N:3]2[CH:9]=[C:8]([C:10]3[CH:15]=[CH:14][C:13]([NH2:16])=[CH:12][CH:11]=3)[N:7]=[C:4]2[S:5][CH:6]=1
Reactant: Cc1csc2nc(-c3ccc([N+](=O)[O-])cc3)cn12
Agent: Cl[Sn]Cl
Solvent: ClCCl
Solvent: O
Solvent: CCO
Product: Cc1csc2nc(-c3ccc(N)cc3)cn12
Yield: 49.7 %

Procedure:
Prepared as described in the Nitro Reduction section using 3-methyl-6-(4-nitrophenyl)imidazo[2,1-b][1,3]thiazole (0.20 g, 0.772 mmol) and tin (II) chloride dihydrate (0.87 g, 3.86 mmol) in EtOH (20 ml) to give the title compound (88 mg, 50%) as a pale orange solid after work-up and flash chromatography (1:1 DCM/EtOAc).
Reaction SMILES: [CH:1]1([NH:6][C:7]2[CH:8]=[CH:9][CH:10]=[C:11]3[C:15]=2[NH:14][C:13]([C:16]2[S:17][CH2:18][C@@H:19]([CH2:21][C:22]([OH:24])=O)[N:20]=2)=[CH:12]3)[CH2:5][CH2:4][CH2:3][CH2:2]1.O[NH:26][C:27]([N:29]1[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1)=[NH:28]>>[CH:1]1([NH:6][C:7]2[CH:8]=[CH:9][CH:10]=[C:11]3[C:15]=2[NH:14][C:13]([C:16]2[S:17][CH2:18][C@@H:19]([CH2:21][C:22]4[O:24][N:28]=[C:27]([N:29]5[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]5)[N:26]=4)[N:20]=2)=[CH:12]3)[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=C(O)C[C@@H]1CSC(c2cc3cccc(NC4CCCC4)c3[nH]2)=N1
Reactant: N=C(NO)N1CCCCC1
Product: c1cc(NC2CCCC2)c2[nH]c(C3=N[C@H](Cc4nc(N5CCCCC5)no4)CS3)cc2c1
Yield: 54 %

Procedure:
The compound (140 mg, 0.41 mmol) prepared in Example 42 and N-hydroxypiperidinecarboxamidine instead of N-hydroxycyclopentanecarboxamidine were reacted according to the same procedure as Example 172 to give the title compound (100 mg, Yield 54%).
Reaction SMILES: [NH2:1][C:2]1[N:10]=[C:9]([O:11][CH2:12][CH2:13][O:14][CH3:15])[N:8]=[C:7]2[C:3]=1[N:4]=[C:5]([O:25]C)[N:6]2[CH2:16][C:17]1[CH:18]=[C:19]([CH2:23][OH:24])[CH:20]=[CH:21][CH:22]=1.O1CCOCC1.C(O)(C(F)(F)F)=O.N>CO.O>[OH:24][CH2:23][C:19]1[CH:18]=[C:17]([CH:22]=[CH:21][CH:20]=1)[CH2:16][N:6]1[C:5]([OH:25])=[N:4][C:3]2[C:7]1=[N:8][C:9]([O:11][CH2:12][CH2:13][O:14][CH3:15])=[N:10][C:2]=2[NH2:1]
Reactant: COCCOc1nc(N)c2nc(OC)n(Cc3cccc(CO)c3)c2n1
Agent: N
Solvent: O=C(O)C(F)(F)F
Solvent: CO
Solvent: C1COCCO1
Product: COCCOc1nc(N)c2nc(O)n(Cc3cccc(CO)c3)c2n1
Yield: 212.9 %

Procedure:
A solution of Compound (7) (371.2 mg, 1.03 mmol) in a 1:1 p-dioxane:TFA (“trifluoroacetic acid”) mixture, and a catalytic amount of water was heated to 65° C. for 24 hrs. Evaporation of the solvent showed that a trifluoroacetyl adduct had formed. The adduct was converted to the desired diol by stirring in a saturated ammonia in methanol solution. Evaporation of the methanol gave Compound (8) (757.3 mg, 213%) as a white solid. (The large excess in recovery is most likely due to the presence of salts remaining in the mixture.) 1H NMR (300 MHz, DMSO) δ 3.26 (s, 3H), 3.57 (t, J=4.8, 9.3 Hz), 4.25 (t, J=4.8, 9.6 Hz, 2H), 4.43 (d, J=5.1, 2H), 7.32 (m, 4H). LCMS: m/z for C16H19N5O4++H observed 346.1 at 1.69 minutes of a 3.5 minute run, gradient 5-95% CH3CN in H2O (C18 column).
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]([CH3:11])=[C:5]([C:7]([O:9]C)=[O:8])[N:6]=1.[F:12][C:13]1[CH:14]=[C:15]([C:20]2[S:24][C:23]([S:25](Cl)(=[O:27])=[O:26])=[CH:22][CH:21]=2)[CH:16]=[C:17]([F:19])[CH:18]=1.N1C=CC=CC=1>CC#N>[F:12][C:13]1[CH:14]=[C:15]([C:20]2[S:24][C:23]([S:25]([NH:1][C:2]3[S:3][C:4]([CH3:11])=[C:5]([C:7]([OH:9])=[O:8])[N:6]=3)(=[O:27])=[O:26])=[CH:22][CH:21]=2)[CH:16]=[C:17]([F:19])[CH:18]=1
Reactant: COC(=O)c1nc(N)sc1C
Reactant: O=S(=O)(Cl)c1ccc(-c2cc(F)cc(F)c2)s1
Solvent: c1ccncc1
Solvent: CC#N
Product: Cc1sc(NS(=O)(=O)c2ccc(-c3cc(F)cc(F)c3)s2)nc1C(=O)O
Temperature: 25 °C
Yield: 9 %

Procedure:
A solution of methyl 2-amino-5-methyl-1,3-thiazole-4-carboxylate (25 mg, 0.15 mmol), 5-(3,5-difluorophenyl)thiophene-2-sulfonyl chloride (43 mg, 0.15 mmol) (Intermediate 21) and pyridine (23 mg, 0.29 mmol) in MeCN (1 mL) was stirred at 50° C. for 2 days. After evaporation of the solvents, the residue was dissolved in THF (1 mL) and 2 M LiOH (1 mL) was added. The reaction mixture was stirred at room temperature over night. The reaction mixture was neutralized with 4 M HCl (0.3 mL) and the solvents were removed by evaporation. The crude material was dissolved in MeCN/water (1:1). The product precipitated and the title compound was obtained in 9% yield (5.8 mg). 1H NMR (400 MHz, MeOH-d4) δ ppm 2.56 (s, 3 H) 6.97 (tt, J=9.05, 2.27 Hz, 1 H) 7.26-7.34 (m, 2 H) 7.45 (d, J=3.91 Hz, 1 H) 7.58 (d, J=3.91 Hz, 1 H). MS (ESI+) m/z 417 [M+H]+.
Reaction SMILES: [C:1]([O:5][C:6](=[O:19])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][C:10]=1[C:17]#[CH:18])([CH3:4])([CH3:3])[CH3:2].[F:20][C:21]1[CH:26]=[CH:25][C:24]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH:23][C:22]=1I>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C1COCC1>[C:1]([O:5][C:6](=[O:19])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][C:10]=1[C:17]#[C:18][C:22]1[CH:23]=[C:24]([S:27]([CH3:30])(=[O:28])=[O:29])[CH:25]=[CH:26][C:21]=1[F:20])([CH3:4])([CH3:3])[CH3:2]
Reactant: C#Cc1cc(C#N)ccc1OCC(=O)OC(C)(C)C
Reactant: CS(=O)(=O)c1ccc(F)c(I)c1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: c1ccc(P(c2ccccc2)[c-]2cccc2)cc1
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)COc1ccc(C#N)cc1C#Cc1cc(S(C)(=O)=O)ccc1F
Temperature: 70 °C
Reaction time: 16 h
Yield: 77.6 %

Procedure:
A suspension of (4-cyano-2-ethynyl-phenoxy)-acetic acid tert-butyl ester (Intermediate 46; 200 mg; 0.78 mmol), 1-fluoro-2-iodo-4-(methylsulfonyl)benzene (Intermediate 77; 233 mg; 0.78 mmol), 1,1′-bis(diphenylphosphino)ferrocenedichloro palladium(II) (34 mg; 0.05 mmol) and cuprous iodide (9 mg; 0.05 mmol) was degassed during 2 minutes under nitrogen then anhydrous THF (3 ml) and TEA (215 μl; 1.55 mmol) were added and the reaction mixture was stirred at 70° C. for 16 hours. The solvents were removed under reduced pressure and the residue was purified by flash column chromatography (silica), eluting with cyclohexane containing increasing amounts of EtOAc to give the title compound (260 mg, 78%) as a yellow sticky solid.
Reaction SMILES: ClC1C=CC=C(C(OO)=O)C=1.[CH3:12][O:13][C:14](=[O:28])[C:15]1[CH:20]=[CH:19][C:18]([C:21]#[C:22][CH2:23][N:24]([CH3:26])[CH3:25])=[CH:17][C:16]=1[Cl:27].C(OCC)C>ClCCl>[CH3:12][O:13][C:14](=[O:28])[C:15]1[CH:20]=[CH:19][C:18]([CH2:21][CH:22]=[CH:23][N:24]([CH3:25])[CH3:26])=[CH:17][C:16]=1[Cl:27]
Reactant: COC(=O)c1ccc(C#CCN(C)C)cc1Cl
Agent: O=C(OO)c1cccc(Cl)c1
Solvent: CCOCC
Solvent: ClCCl
Product: COC(=O)c1ccc(CC=CN(C)C)cc1Cl
Temperature: 60 °C
Reaction time: 0.5 h
Yield: 26 %

Procedure:
Under an atmosphere of nitrogen, purified meta-chloroperbenzoic acid (16.0 g, 93 mmol) was added portionwise to a stirred solution of 2-chloro-4-(3-dimethylaminopropyn-1-yl)-benzoic acid methyl ester of Step A (23.5 g, 93.4 mmol) in 200 mL of dichloromethane at −10° C. After the addition was complete, the solution was stirred at reduced temperature for 30 minutes and then filtered through a column of basic alumina (400 g, Brockman activity I) packed with dichloromethanemethanol (9:1, v/v). The intermediate N-oxide was eluted with the above solvent system. The dichloromethane was then carefully replaced with methanol by evaporation at or below room temperature, taking care that the mixture is never allowed to evaporate to dryness. The methanolic solution was heated at 60° C. overnight, and then was concentrated in vacuo. The residue was purified by flash chromatography (on Merck-60 silica gel, hexane-ethyl acetate 1:1) to give 12.1 g of a slightly impure product. Trituration with diethyl ether provided the pure title compound (6.15 g) as an orange solid.
Reaction SMILES: Cl[C:2]1[C:11]2[CH:10]=[C:9]3[N:12]=[CH:13][N:14]=[C:8]3[CH2:7][C:6]=2[N:5]=[CH:4][C:3]=1[C:15]#[N:16].Cl.[Cl:18][C:19]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][C:20]=1[NH2:21].Cl.N1C=CC=CC=1.C(=O)(O)[O-].[Na+]>C(OCCO)C>[Cl:18][C:19]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][C:20]=1[NH:21][C:2]1[C:11]2[CH:10]=[C:9]3[N:12]=[CH:13][N:14]=[C:8]3[CH2:7][C:6]=2[N:5]=[CH:4][C:3]=1[C:15]#[N:16]
Reactant: COc1ccc(Cl)c(N)c1
Reactant: N#Cc1cnc2c(c1Cl)C=C1N=CN=C1C2
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOCCO
Solvent: c1ccncc1
Product: COc1ccc(Cl)c(Nc2c(C#N)cnc3c2C=C2N=CN=C2C3)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 62.4 %

Procedure:
A mixture of 0.2 g (0.87 mmol) of 8-chloroimidazo[4,5-g]quinoline-7-carbonitrile, 0.22 g (1.04 mmol) of 2-chloro-5-methoxyaniline hydrochloride and 0.1 g (0.87 mmol) of pyridine hydrochloride in 5.0 mL of 2-ethoxyethanol is heated at reflux temperature for 1 hour, cooled to room temperature, poured into a saturated solution of sodium bicarbonate and stirred for 0.5 hour. The solid is collected by filtration, washed with water and dried. The solid is purified by silica gel chromatography utilizing a gradient of methylene chloride/methanol (97:3 to 90:10) to yield 0.19 g of 8-(2-chloro-5-methoxy-phenylamino)imidazo[4,5-g]quinoline-7-carbonitrile as beige solid, mp 296–298° C.
Reaction SMILES: [CH2:1]([C:3]1([CH2:10][O:11][C:12](=[O:16])[C:13]([CH3:15])=[CH2:14])[CH2:8][O:7][C:6](=[O:9])[O:5][CH2:4]1)[CH3:2].[CH3:17][OH:18].C1(C)C=CC(S(O)(=O)=O)=CC=1>ClCCCl>[CH2:1]([C:3]([CH2:10][O:11][C:12](=[O:16])[C:13]([CH3:15])=[CH2:14])([CH2:8][O:7][C:6]([O:5][CH3:4])=[O:9])[CH2:17][OH:18])[CH3:2]
Reactant: C=C(C)C(=O)OCC1(CC)COC(=O)OC1
Reactant: CO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: ClCCCl
Product: C=C(C)C(=O)OCC(CC)(CO)COC(=O)OC
Temperature: 40 °C
Reaction time: 2 h

Procedure:
11.4 g of 5-ethyl-5-methacryloyloxymethyl-2-oxo-1,3-dioxane, 3.2 g of methanol and 0.285 g of p-toluenesulfonic acid were dissolved in 100 g of 1,2-dichloroethane. The solution was stirred for 2 hours at 40° C. and evaporated in vacuo to remove the solvent. After removing white precipitates by filtration, the residue was further concentrated whereupon the title compound was recovered as a colorless oil.
Reaction SMILES: [CH3:1][C:2]1([CH3:14])[CH2:7][O:6][C:5]2([CH2:12][CH2:11][C:10](=O)[CH2:9][CH2:8]2)[O:4][CH2:3]1.[C:15]([CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])#[N:16].N1CCCCC1.C(O)(=O)C>C(O)C>[CH2:21]([O:20][C:18](=[O:19])[C:17]([C:15]#[N:16])=[C:10]1[CH2:11][CH2:12][C:5]2([O:6][CH2:7][C:2]([CH3:14])([CH3:1])[CH2:3][O:4]2)[CH2:8][CH2:9]1)[CH3:22]
Reactant: CC1(C)COC2(CCC(=O)CC2)OC1
Reactant: CCOC(=O)CC#N
Solvent: C1CCNCC1
Solvent: CC(=O)O
Solvent: CCO
Product: CCOC(=O)C(C#N)=C1CCC2(CC1)OCC(C)(C)CO2
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 3,3-dimethyl-1,5-dioxa-spiro[5.5]undecan-9-one (10.0 g), ethyl cyanoacetate (5.9 mL), piperidine (0.5 mL), acetic acid (0.3 mL), and ethanol (100 mL) is stirred at room temperature overnight. The mixture is then cooled to −5° C. and the precipitate formed is separated by filtration, washed with ice-cold ethanol, and dried to give the title compound as a colorless solid. Yield: 13.7 g (93% of theory); Mass spectrum (ESI+): m/z=294 [M+H]+.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][C@H:11]2[CH2:16][CH2:15][C@H:14]([O:17][CH2:18][C:19]([N:21]3[CH2:26][CH2:25][N:24]([C:27]4[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][CH:28]=4)[CH2:23][CH2:22]3)=[O:20])[CH2:13][CH2:12]2)=[CH:6][C:5]=1[C:37]([F:40])([F:39])[F:38])([O-:3])=[O:2].[H-].[Na+].[CH3:43]I>O1CCCC1>[CH3:43][N:10]([C:7]1[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[C:5]([C:37]([F:40])([F:39])[F:38])[CH:6]=1)[C@H:11]1[CH2:16][CH2:15][C@H:14]([O:17][CH2:18][C:19]([N:21]2[CH2:22][CH2:23][N:24]([C:27]3[CH:32]=[CH:31][C:30]([C:33]([F:34])([F:35])[F:36])=[CH:29][CH:28]=3)[CH2:25][CH2:26]2)=[O:20])[CH2:13][CH2:12]1
Reactant: O=C(CO[C@H]1CC[C@H](Nc2ccc([N+](=O)[O-])c(C(F)(F)F)c2)CC1)N1CCN(c2ccc(C(F)(F)F)cc2)CC1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CN(c1ccc([N+](=O)[O-])c(C(F)(F)F)c1)[C@H]1CC[C@H](OCC(=O)N2CCN(c3ccc(C(F)(F)F)cc3)CC2)CC1

Procedure:
2-[Trans-4-(4-nitro-3-trifluoromethyl-phenylamino)-cyclohexyloxy]-1-[4-(4-trifluoromethyl-phenyl)-piperazin-1-yl]-ethanone (172 mg, 0.30 mmol, prepared in accordance with Example 11) and sodium hydride (12 mg, 0.30 mmol) were placed under an inert atmosphere. Dry tetrahydrofuran (3 mL) was then added. After gas evolution ceased, methyl iodide (20 μL, 0.31 mmol) was added under stirring to the dark orange colored solution. The resulting mixture was stirred at room temperature. After an hour, HPLC-MS monitoring of the reaction showed about 75% conversion to the desired product. More methyl iodide was added (5 μL, 0.08 mmol), and the mixture was stirred for an additional 30 min. HPLC-MS showed 85% conversion. The mixture was quenched with saturated aqueous ammonium chloride (10 mL) and extracted with ethyl acetate (25 mL). The organic layer was separated, washed with water (10 mL), dried over magnesium sulfate, filtered, and concentrated under vacuum. A yellow oil was isolated. The oil was purified by preparative HPLC. Following lyophilization of the fractions of interest, the desired product was isolated as a yellow solid (106 mg, 59% yield). The structure was confirmed using Protocol I-A. Calculated mass=589; observed mass=589; HPLC retention time=4.69 min.
Reaction SMILES: ON1C2N=CC=CC=2N=N1.[F:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[C:18]1[CH:19]=[N:20][C:21]([N:24]2[C:32]3[C:27](=[CH:28][CH:29]=[C:30]([C:33](O)=[O:34])[CH:31]=3)[C:26]([CH3:36])=[CH:25]2)=[N:22][CH:23]=1.[O:37]1[CH2:42][CH2:41][CH2:40][NH:39][CH2:38]1.C(N(C(C)C)CC)(C)C>ClCCl>[F:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[C:18]1[CH:19]=[N:20][C:21]([N:24]2[C:32]3[C:27](=[CH:28][CH:29]=[C:30]([C:33]([N:39]4[CH2:40][CH2:41][CH2:42][O:37][CH2:38]4)=[O:34])[CH:31]=3)[C:26]([CH3:36])=[CH:25]2)=[N:22][CH:23]=1
Reactant: Cc1cn(-c2ncc(-c3ccccc3F)cn2)c2cc(C(=O)O)ccc12
Reactant: C1CNCOC1
Agent: On1nnc2cccnc21
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: Cc1cn(-c2ncc(-c3ccccc3F)cn2)c2cc(C(=O)N3CCCOC3)ccc12
Temperature: 25 °C
Reaction time: 18 h

Procedure:
EDCxHCl (109 mg, 0.57 mmol) and 1-hydroxy-7-azabenzotriazole (17 mg, 0.12 mmol) were added to a solution of acid 89b) (200 mg, 0.50 mmol), 1,3-oxazinane (43.1 mg, 0.50 mmol) and diisopropylethylamine (0.13 mL, 0.74 mmol) in dichloromethane (2 mL) and the reaction mixture was stirred at room temperature for 18 h. The solvent was evaporated and the residue purified by column chromatography [silica, heptane with 5 to 100% ethyl acetate]. White solid. Yield: 51 mg. HPLC-MS: m/z [M+H]+=417.2
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:11]=[C:12]([S:14]([F:19])([F:18])([F:17])([F:16])[F:15])[CH:13]=1)[C:5](N(OC)C)=[O:6].[CH3:20]OC1C=C(C(=O)C)C=C(S(F)(F)(F)(F)F)C=1>>[Br:1][C:2]1[CH:3]=[C:4]([C:5](=[O:6])[CH3:20])[CH:11]=[C:12]([S:14]([F:19])([F:18])([F:17])([F:16])[F:15])[CH:13]=1
Reactant: COc1cc(C(C)=O)cc(S(F)(F)(F)(F)F)c1
Reactant: CON(C)C(=O)c1cc(Br)cc(S(F)(F)(F)(F)F)c1
Product: CC(=O)c1cc(Br)cc(S(F)(F)(F)(F)F)c1

Procedure:
3-Bromo-N-methoxy-N-methyl-5-(pentafluorosulfanyl)benzamide (1.1 g) was converted and worked up analogously to 21d). Purification by means of HPLC was not necessary. 935 mg of the title compound were obtained.
Reaction SMILES: [N:1]([CH2:4][C:5]1[C:6]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[N:7][C:8]2[C:13]([C:14]=1[C:15]([NH:17][C@H:18]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH2:19][CH3:20])=[O:16])=[CH:12][CH:11]=[CH:10][CH:9]=2)=[N+]=[N-].Cl>C(O)C.[Pd]>[NH2:1][CH2:4][C:5]1[C:6]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)=[N:7][C:8]2[C:13]([C:14]=1[C:15]([NH:17][C@H:18]([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[CH2:19][CH3:20])=[O:16])=[CH:12][CH:11]=[CH:10][CH:9]=2
Reactant: CC[C@H](NC(=O)c1c(CN=[N+]=[N-])c(-c2ccccc2)nc2ccccc12)c1ccccc1
Agent: [Pd]
Agent: Cl
Solvent: CCO
Product: CC[C@H](NC(=O)c1c(CN)c(-c2ccccc2)nc2ccccc12)c1ccccc1
Reaction time: 1.5 h
Yield: 100.3 %

Procedure:
A solution of 3-(azidomethyl)-2-phenyl-N-[(1s)-1-phenylpropyl]quinoline-4-carboxamide (2d) (1000 mg, 2.37 mmol) in ethanol (200 mL) were added Pd/C (10%, 1190 mg) and HCl (2N, 2.5 mL) was added. The reaction mixture were hydrogenated under 50 psi H2 at RT for 1.5 h. The catalyst was removed by filtration through a thick layer of diatomaceous earth, the filter was washed with ethanol and the washes and the ethanol solvent was combined and concentrated in vacuo. Crystallization from dichloromethane and ether afforded the title compound (940 mg, 92%) as a hydrogen chloride salt. 1H NMR (300 MHz, CDCl3) δ 0.92 (t, 3H), 2.01 (m, 2H), 3.18 (b, 3H), 4.39 (t, 2H), 5.16 (q, 1H), 7.30 (d, 2H), 7.34 (d, 2H), 7.39 (m, 1H), 7.78 (m, 2H), 7.84 (m, 2H), 8.08 (m, 1H), 8.30 (m, 2H), 8.44 (m, 2H). MS APCI, m/z=396 (M+1). LCMS: 1.70 min.
Reaction SMILES: [Sn](Cl)Cl.[CH2:4]([O:7][C:8]([NH:10][CH:11]([C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([N+:24]([O-])=O)[CH:19]=1)[CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])=[O:9])[CH:5]=[CH2:6].[OH-].[Na+]>C(O)C>[CH2:4]([O:7][C:8]([NH:10][CH:11]([C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([NH2:24])[CH:19]=1)[CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])=[O:9])[CH:5]=[CH2:6]
Reactant: C=CCOC(=O)NC(CC(=O)OCC)c1cccc([N+](=O)[O-])c1
Agent: Cl[Sn]Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: C=CCOC(=O)NC(CC(=O)OCC)c1cccc(N)c1

Procedure:
Tin(II) chloride (64.6 g) was added to a solution of ethyl 3-allyloxycarbonylamino-3-(3-nitrophenyl)-propionate from II.1c (18.8 g) in 245 ml of ethanol, and the reaction mixture was heated under reflux for 2 h. After cooling the solution, it was adjusted to pH=7 using 2N NaOH, briefly heated, cooled again and filtered. It was then extracted with dichloromethane, and the org. phase was dried (MgSO4) and concentrated. 10.9 g of product were obtained.
Reaction SMILES: [C:1]1([S:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH:15]=1.[H+].[B-](F)(F)(F)F.[F:26][Sb-:27]([F:32])([F:31])([F:30])([F:29])[F:28].[Na+]>CC(C)=O.CCOCC>[F:26][Sb-:27]([F:32])([F:31])([F:30])([F:29])[F:28].[CH:8]1([S+:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]1
Reactant: C1=CCCCC1
Reactant: c1ccc(Sc2ccccc2)cc1
Agent: F[B-](F)(F)F
Agent: F[Sb-](F)(F)(F)(F)F
Agent: [H+]
Solvent: CCOCC
Solvent: CC(C)=O
Product: c1ccc([S+](c2ccccc2)C2CCCCC2)cc1
Temperature: 25 °C

Procedure:
1 mol of diphenyl sulfide is dissolved in an excess of cyclohexene and and to the solution is added 1 mol of HBF4 (54% etherate) and the mixture is stirred at room temperature. After c. 15 minutes a second phase forms. The product is isolated by addition of ether and dissolved in acetone. Afterwards, sodium hexafluoroantimonate is added to the solution and the resulting cyclohexyldiphenylsulfonium hexafluoroantimonate is precipitated by addition of water. The compound has a melting point of 129° C. and the analytical data obtained are as follows:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]([OH:29])[CH2:9][NH:10][CH:11]([CH3:28])[CH2:12][C:13]2[CH:27]=[CH:26][C:16]3[O:17][C:18]([C:23]([OH:25])=[O:24])([C:20]([OH:22])=[O:21])[O:19][C:15]=3[CH:14]=2)[CH:5]=[CH:6][CH:7]=1.[CH3:30][C:31]([CH3:36])([CH3:35])[CH2:32][CH2:33]O.Cl.[K+].[Br-]>C(Cl)(Cl)Cl>[CH3:30][C:31]([CH3:36])([CH3:35])[CH2:32][CH2:33][O:24][C:23]([C:18]1([C:20]([O:22][CH2:33][CH2:32][C:31]([CH3:36])([CH3:35])[CH3:30])=[O:21])[O:17][C:16]2[CH:26]=[CH:27][C:13]([CH2:12][CH:11]([NH:10][CH2:9][CH:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=3)[OH:29])[CH3:28])=[CH:14][C:15]=2[O:19]1)=[O:25]
Reactant: CC(C)(C)CCO
Reactant: CC(Cc1ccc2c(c1)OC(C(=O)O)(C(=O)O)O2)NCC(O)c1cccc(Cl)c1
Agent: Cl
Agent: [Br-]
Agent: [K+]
Solvent: ClC(Cl)Cl
Product: CC(Cc1ccc2c(c1)OC(C(=O)OCCC(C)(C)C)(C(=O)OCCC(C)(C)C)O2)NCC(O)c1cccc(Cl)c1

Procedure:
The title compound was prepared from 5-{2-[2-(3-chloro-phenyl)-2-hydroxy-ethylarnino]-propyl}-benzo[1,3]dioxole-2,2-dicarboxylic acid and 3,3-dimethylbutanol according to the procedure of Example 30 as a white foam (HCl salt); 1H NMR (CDCl3) δ 0.90 (s, 18H), 1.33 (bs, 3H), 1.62 (t, J=7.4 Hz, 4H), 2.80 (bs, 1H), 3.18 (bs, 2H), 3.48 (bs, 2H), 4.35 (t, J=7.4 Hz, 4H), 5.45 (bs, 1H), 6.80 (m, 3 H), 7.26 (m, 2H), 7.43 (s, 1H), 8.70 (bs, 1H), 10.10 (bs, 1H); IR (KBr): 1765 cm-1 (C=O); MS (CI) m/z 590 (MH+); [α]D5 -24° (c, 1.0, CHCl3). Anal. Calcd. for C32H44ClNO7 ·HCl: C, 61.34; H, 7.08; N, 2.24; Cl, 11.32. Found: C, 60.79; H, 7.46; N, 2.09; Cl, 11.95.