Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C1(C)C=CC(S([O-])(=O)=O)=CC=1.[CH2:12]([N:14]1[C:18](=[O:19])[C:17](=[C:20]2[N:24]([CH3:25])[C:23]3[CH:26]=[CH:27][CH:28]=[CH:29][C:22]=3[S:21]2)[S:16][CH2+:15]1SC)[CH3:13].[NH2:32][C:33]1[CH:34]=[C:35]2[C:40](=[CH:41][CH:42]=1)[N:39]=[CH:38][CH:37]=[CH:36]2>>[CH2:12]([N:14]1[C:18](=[O:19])[C:17](=[C:20]2[N:24]([CH3:25])[C:23]3[CH:26]=[CH:27][CH:28]=[CH:29][C:22]=3[S:21]2)[S:16][C:15]1=[N:32][C:33]1[CH:34]=[C:35]2[C:40](=[CH:41][CH:42]=1)[N:39]=[CH:38][CH:37]=[CH:36]2)[CH3:13]
Reactant: CCN1C(=O)C(=C2Sc3ccccc3N2C)S[CH2+]1SC
Reactant: Nc1ccc2ncccc2c1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Product: CCN1C(=O)C(=C2Sc3ccccc3N2C)SC1=Nc1ccc2ncccc2c1

Procedure:
The title compound was prepared from 3-ethyl-5-(3-methyl-3H-benzothiazol-2-ylidene)-2-methylthio-4-oxo-2-thiazolium p-toluenesulfonate and 6-aminoquinoline in a manner similar to that described in Example 1. 1H-NMR (CDCl3): δ 8.85 (1H, dd), 8.11 (1H, d), 8.10 (1H, d), 7.51 (1H, dd) 7.46 (1H, dd), 7.40 (1H, d), 7.38 (1H, dd), 7.32 (1H, m), 7.16 (1H, m), 7.01 (1H, d), 4.10 (2H, q), 3.70 (3H, s), 1.41 (3H, t); MS(ESI): 419 (MH+).
Reaction SMILES: [CH:1]1([C@H:7]([NH:28]C(=O)OC(C)(C)C)[C:8](=[O:27])[N:9]2[C:13]3=[N:14][CH:15]=[CH:16][CH:17]=[C:12]3[CH2:11][C@H:10]2[C:18](=[O:26])[NH:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[C:20]1([NH:19][C:18]([C@H:10]2[N:9]([C:8](=[O:27])[C@@H:7]([NH2:28])[CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]3)[C:13]3=[N:14][CH:15]=[CH:16][CH:17]=[C:12]3[CH2:11]2)=[O:26])[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: CC(C)(C)OC(=O)N[C@H](C(=O)N1c2ncccc2C[C@H]1C(=O)Nc1ccccc1)C1CCCCC1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: N[C@H](C(=O)N1c2ncccc2C[C@H]1C(=O)Nc1ccccc1)C1CCCCC1
Reaction time: 1 h
Yield: 77.7 %

Procedure:
For Intermediate 3: In a 100 mL round-bottomed flask, tert-butyl (S)-(1S)-1-cyclohexyl-2-oxo-2-(2-(phenylcarbamoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-1-yl)ethylcarbamate (130 mg, 272 μmol, Eq: 1.00) was combined with DCM (2.6 mL) to give a colorless solution. TFA (2.6 mL, 33.7 mmol, Eq: 124) was added and the reaction was stirred for 1 h. The crude reaction mixture was concentrated in vacuo. The residue was dissolved in DCM (20 mL), washed with saturated aqueous NaHCO3 (5 mL). The organic layer was dried over Na2SO4 and concentrated in vacuo to give (S)-1-((S)-2-amino-2-cyclohexyl-acetyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid phenylamide as a colorless oil (80 mg), m/z=379 (M+H).
Reaction SMILES: [CH2:1]([NH:8][C:9]1[CH:28]=[CH:27][C:12]([CH2:13][NH:14][C:15]([C:17]2[CH:18]=[C:19]3[C:24](=[CH:25][CH:26]=2)[N:23]=[CH:22][CH:21]=[CH:20]3)=[O:16])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=C[C:30]=1OCC1C=CC(CNC(C2C(N)=NC(N)=CN=2)=O)=CC=1.C=O.C(=O)(O)[O-].[Na+]>C(O)(=O)C.O1CCCC1>[CH2:1]([N:8]([CH3:30])[C:9]1[CH:10]=[CH:11][C:12]([CH2:13][NH:14][C:15]([C:17]2[CH:18]=[C:19]3[C:24](=[CH:25][CH:26]=2)[N:23]=[CH:22][CH:21]=[CH:20]3)=[O:16])=[CH:27][CH:28]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(NCc1ccc(NCc2ccccc2)cc1)c1ccc2ncccc2c1
Reactant: Nc1cnc(C(=O)NCc2ccc(COc3ccccn3)cc2)c(N)n1
Agent: C=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CC(=O)O
Product: CN(Cc1ccccc1)c1ccc(CNC(=O)c2ccc3ncccc3c2)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 35 %

Procedure:
Quinoline-6-carboxylic acid 4-benzylamino-benzylamide described in Preparation Example E+-3 (30 mg, 82 μmol), formalin (9 μl, 115 μmol), triacetoxy sodium borohydride (25 mg, 115 μmol) and acetic acid (several drops) were suspended in tetrahydrofuran (1 mL), and the solution was stirred at room temperature for 4 hours. An aqueous solution of saturated sodium bicarbonate was added to the reaction suspension at 0° C., which was then extracted with ethyl acetate, the organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated in vacuo, purification was carried out using thin layer NH silica gel chromatography (hexane:ethyl acetate=1:1), and the title compound (11 mg, 28 μmol, 35%) was obtained as a white solid.
Reaction SMILES: [F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].FC(F)(F)C(O)=O.[Cl:15][C:16]1[CH:17]=[N:18][C:19]2[NH:20][C:21]3[CH:22]=[CH:23][CH:24]=[C:25]([CH:47]=3)[CH2:26][CH2:27][C:28]3[CH:36]=[C:32]([NH:33][C:34]=1[N:35]=2)[CH:31]=[CH:30][C:29]=3[NH:37][C:38](=[O:46])[CH2:39][CH:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1.[CH3:48][N:49]([CH3:53])[C:50](Cl)=[O:51]>>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[Cl:15][C:16]1[CH:17]=[N:18][C:19]2[NH:20][C:21]3[CH:22]=[CH:23][CH:24]=[C:25]([CH:47]=3)[CH2:26][CH2:27][C:28]3[CH:36]=[C:32]([NH:33][C:34]=1[N:35]=2)[CH:31]=[CH:30][C:29]=3[NH:37][C:38](=[O:46])[CH2:39][CH:40]1[CH2:45][CH2:44][N:43]([C:50]([N:49]([CH3:53])[CH3:48])=[O:51])[CH2:42][CH2:41]1
Reactant: O=C(CC1CCNCC1)Nc1ccc2cc1CCc1cccc(c1)Nc1ncc(Cl)c(n1)N2
Reactant: CN(C)C(=O)Cl
Solvent: O=C(O)C(F)(F)F
Product: CN(C)C(=O)N1CCC(CC(=O)Nc2ccc3cc2CCc2cccc(c2)Nc2ncc(Cl)c(n2)N3)CC1
Yield: 48 %

Procedure:
The desired compound was prepared according to the procedure of Example A9, step H using N-[6-chloro-2,4,8,22-tetraazatetracyclo[14.3.1.1(3,7).1(9,13)]docosa-1(20), 3(22),4,6,9(21),10,12,16,18-nonaen-12-yl]-2-piperidin-4-ylacetamide bis(trifluoroacetate) and N,N-dimethylcarbamoyl chloride as starting materials in 48% yield. 1H NMR (300 MHz, DMSO-d6): δ 9.57 (s, 1H), 9.43 (s, 1H), 9.32 (s, 1H), 8.17 (s, 1H), 7.97 (s, 1H), 7.72 (s, 1H), 7.21 (d, 1H), 7.10 (m, 1H), 7.01 (d, 1H), 6.88 (d, 1H), 6.80 (d, 1H), 3.57 (d, 2H), 2.91 (m, 2H), 2.83 (m, 2H), 2.71 (m, 8H), 2.32 (d, 2H), 1.93 (m, 1H), 1.70 (m, 2H), 1.20 (m, 2H). LCMS for C28H33ClN7O2 (M+H)+: m/z=534.2.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:12]([C:15](=O)[C:16]([F:19])([F:18])[F:17])[C:13]#[N:14])[CH:5]=[C:6]([Cl:11])[C:7]=1[N:8]([CH3:10])[CH3:9].O=P(Cl)(Cl)[Cl:23].C(N(CC)CC)C>O>[Cl:23]/[C:15](/[C:16]([F:19])([F:18])[F:17])=[C:12](\[C:4]1[CH:3]=[C:2]([Cl:1])[C:7]([N:8]([CH3:10])[CH3:9])=[C:6]([Cl:11])[CH:5]=1)/[C:13]#[N:14]
Reactant: CN(C)c1c(Cl)cc(C(C#N)C(=O)C(F)(F)F)cc1Cl
Reactant: O=P(Cl)(Cl)Cl
Solvent: O
Solvent: CCN(CC)CC
Product: CN(C)c1c(Cl)cc(/C(C#N)=C(\Cl)C(F)(F)F)cc1Cl

Procedure:
1 g (3.07 mmol) of 2-[3,5-dichloro-4-(dimethylamino)phenyl]-4,4,4-trifluoro-3-oxobutanenitrile is initially charged in 1.44 ml of POCl3 (15.3 mmol), and 0.43 ml (3.07 mmol) of triethylamine are added slowly. The reaction mixture is then stirred under reflux for 5 hours. After cooling, water is added carefully and the mixture is extracted repeatedly with dichloromethane. The separated organic phases are combined, dried over magnesium sulphate, filtered and concentrated. The residue is used without further purification for the next step.
Reaction SMILES: [CH3:1][Li].[C:3]1([C@@H:9]([CH3:14])[CH2:10][C:11]([OH:13])=O)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1>CCOCC>[C:3]1([C@@H:9]([CH3:14])[CH2:10][C:11](=[O:13])[CH3:1])[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1
Reactant: [Li]C
Reactant: C[C@@H](CC(=O)O)c1ccccc1
Solvent: CCOCC
Product: CC(=O)C[C@H](C)c1ccccc1
Temperature: 25 °C

Procedure:
1.6 M Methyl lithium (17.8 mL, 24.9 mmol) was added over 1 hour to a stirring 0° C. solution of (S)-3-Phenylbutyric acid (2.0147 g, 12.18 mmol) in dry Et2O (61 mL, 0.2 M): The ice bath was removed, and the reaction was allowed to stir at room temperature for 1½ additional hours. The reaction was then poured into rapidly stirring ice water containing aq. HCl. The organic layer was removed, washed with NaHCO3 and brine, then dried with Na2SO4, filtered and concentrated to achieve pure 77 (2.0487 g, (2.0487 g, ˜100%): HPLC: 10.081 min. (Note: SM has HPLC retention time of 9.127 min.)
Reaction SMILES: [C:1]([O:5][C:6](=[O:25])[NH:7][C:8]1[CH:13]=[C:12]([S:14]([CH3:17])(=[O:16])=[O:15])[CH:11]=[C:10]([C:18](=O)[CH2:19][CH2:20][CH:21]2[CH2:23][CH2:22]2)[CH:9]=1)([CH3:4])([CH3:3])[CH3:2].O.[NH2:27][NH2:28]>C(O)C>[C:1]([O:5][C:6](=[O:25])[NH:7][C:8]1[CH:13]=[C:12]([S:14]([CH3:17])(=[O:16])=[O:15])[CH:11]=[C:10]([C:18]2[CH:19]=[C:20]([CH:21]3[CH2:23][CH2:22]3)[NH:28][N:27]=2)[CH:9]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)Nc1cc(C(=O)CCC2CC2)cc(S(C)(=O)=O)c1
Reactant: NN
Solvent: O
Solvent: CCO
Product: CC(C)(C)OC(=O)Nc1cc(-c2cc(C3CC3)[nH]n2)cc(S(C)(=O)=O)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 77 %

Procedure:
[3-(3-Cyclopropyl-propionyl)-5-methanesulfonyl-phenyl]-carbamic acid tert-butyl ester (250 mg; 0.688 mmol) was diluted in 5 ml of ethanol and hydrazine hydrate (0.186 ml; 3.439 mmol) was added. The reaction mixture was stirred at room temperature for 1 h. Then, it was concentrated under vacuum. 200 mg (0.53 mmol; 77% yield) of [3-(5-cyclopropyl-1H-pyrazol-3-yl)-5-(methylsulfonyl)-phenyl]-carbamic acid tert butyl ester were obtained.
Reaction SMILES: [CH3:1][N:2]([CH3:19])[C:3]1[CH:18]=[CH:17][C:6]([C:7]([NH:9][C:10]2[CH:16]=[CH:15][C:13]([NH2:14])=[CH:12][CH:11]=2)=[O:8])=[CH:5][CH:4]=1.[N:20]1[C:24]2[CH:25]=[CH:26][C:27]([C:29]([O-])=[O:30])=[CH:28][C:23]=2[NH:22][CH:21]=1>>[CH3:1][N:2]([CH3:19])[C:3]1[CH:4]=[CH:5][C:6]([C:7]([NH:9][C:10]2[CH:16]=[CH:15][C:13]([NH:14][C:29]([C:27]3[CH:26]=[CH:25][C:24]4[NH:20][CH:21]=[N:22][C:23]=4[CH:28]=3)=[O:30])=[CH:12][CH:11]=2)=[O:8])=[CH:17][CH:18]=1
Reactant: O=C([O-])c1ccc2nc[nH]c2c1
Reactant: CN(C)c1ccc(C(=O)Nc2ccc(N)cc2)cc1
Product: CN(C)c1ccc(C(=O)Nc2ccc(NC(=O)c3ccc4[nH]cnc4c3)cc2)cc1

Procedure:
Compound 445 was prepared from 4-(4-dimethylaminobenzamido)aniline and benzimidazole-5-carboxylate by standard conditions. [M+H]+ calcd for C23H21N5O2: 400.17; found: 400.01.
Reaction SMILES: [I:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([CH:11]=[O:12])=[CH:8][CH:9]=2)[NH:4][N:3]=1.C1COCC1.CS(O)(=O)=O.[O:23]1[CH:28]=[CH:27][CH2:26][CH2:25][CH2:24]1>C(Cl)Cl>[I:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([CH:11]=[O:12])=[CH:8][CH:9]=2)[N:4]([CH:24]2[CH2:25][CH2:26][CH2:27][CH2:28][O:23]2)[N:3]=1
Reactant: C1=COCCC1
Reactant: O=Cc1ccc2c(I)n[nH]c2c1
Agent: CS(=O)(=O)O
Solvent: ClCCl
Solvent: C1CCOC1
Product: O=Cc1ccc2c(I)nn(C3CCCCO3)c2c1
Reaction time: 8 h
Yield: 24.4 %

Procedure:
An oven-dried round bottom flask under Ar was charged with 3-iodo-1H-indazole-6-carbaldehyde (50 mg, 0.184 mmol), THF (1.5 mL) and CH2Cl2 (1.0 mL). Methanesulfonic acid (1.4 uL, 0.0221 mmol) was added and the solution cooled with an ice-water bath. A solution of 3,4-dihydro-2H-pyran (41 uL, 0.460 mmol) in CH2Cl2 (0.5 mL) was then added dropwise over 15 minutes and the reaction stirred overnight. The solvents were removed in vacuo and the residue purified by column chromatography (silica gel, 99:1 to 98:2 CH2Cl2/MeOH) to give the title compound as a white powder (16 mg, 25%). 1H NMR (400 MHz, CDCl3) δ 10.18 (s, 1H), 8.13 (s, 1H), 7.77 (d, J=8.4 Hz, 1H), 7.62 (d, J=8.4 Hz, 1H), 5.84-5.77 (m, 1H), 4.07-4.02 (m, 1H), 3.83-3.75 (m, 1H), 2.62-2.51 (m, 1H), 2.20-2.10 (m, 2H), 1.86-1.70 (m, 3H); MS ESI 378.9 [M+Na]+, calcd for [C13H13IN2O2+Na]+ 378.99.
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[C:10]([N:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)[C:9]2[C:4](=[CH:5][C:6]([OH:17])=[CH:7][CH:8]=2)[N:3]=1.Br[CH2:19][C:20]1[C:21]([Cl:30])=[N:22][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:24][CH:25]=1>>[Cl:30][C:21]1[C:20]([CH2:19][O:17][C:6]2[CH:5]=[C:4]3[C:9]([C:10]([N:12]4[CH2:16][CH2:15][CH2:14][CH2:13]4)=[CH:11][C:2]([CH3:1])=[N:3]3)=[CH:8][CH:7]=2)=[CH:25][CH:24]=[C:23]([C:26]([F:27])([F:28])[F:29])[N:22]=1
Reactant: FC(F)(F)c1ccc(CBr)c(Cl)n1
Reactant: Cc1cc(N2CCCC2)c2ccc(O)cc2n1
Product: Cc1cc(N2CCCC2)c2ccc(OCc3ccc(C(F)(F)F)nc3Cl)cc2n1

Procedure:
In analogy to example 6 there was prepared: on reaction of 2-methyl-4-pyrrolidin-1-yl-quinolin-7-ol with 3-bromomethyl-2-chloro-6-trifluoromethyl-pyridine, whereby the product was isolated as free base, 7-(2-chloro-6-trifluoromethyl-pyridin-3-ylmethoxy)-2-methyl-4-pyrrolidin-1-yl-quinoline as a white solid. ISP mass spectrum, m/e: 422.2 (M+1 calculated for C21H19CIF3N3O: 422).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[N:6]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:7]2[C:12]([C:13](=[O:28])[C:14]=1[CH2:15][NH:16][C:17](=[O:27])[C:18]1[CH:23]=[CH:22][C:21](N(C)C)=[CH:20][CH:19]=1)=[CH:11][CH:10]=[C:9]([O:29][CH3:30])[CH:8]=2)=[O:4].NCC1C(=O)C2C(=CC(OC)=CC=2)N(C2C=CC=CC=2)C=1C(OC)=O.[Cl:62]C1C=CC(C(Cl)=O)=CC=1>>[CH3:1][O:2][C:3]([C:5]1[N:6]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:7]2[C:12]([C:13](=[O:28])[C:14]=1[CH2:15][NH:16][C:17](=[O:27])[C:18]1[CH:23]=[CH:22][C:21]([Cl:62])=[CH:20][CH:19]=1)=[CH:11][CH:10]=[C:9]([O:29][CH3:30])[CH:8]=2)=[O:4]
Reactant: COC(=O)c1c(CNC(=O)c2ccc(N(C)C)cc2)c(=O)c2ccc(OC)cc2n1-c1ccccc1
Reactant: O=C(Cl)c1ccc(Cl)cc1
Agent: COC(=O)c1c(CN)c(=O)c2ccc(OC)cc2n1-c1ccccc1
Product: COC(=O)c1c(CNC(=O)c2ccc(Cl)cc2)c(=O)c2ccc(OC)cc2n1-c1ccccc1

Procedure:
3-[(4-Dimethylamino-benzoylamino)-methyl]-7-methoxy-4-oxo-1-phenyl-1,4-dihydro-quinoline-2-carboxylic acid methyl ester as prepared starting from intermediate K and 4-chloro-benzoyl chloride. MS calcd. for C26H21ClN2O5 [(M+H)+] 477.1, obsd. 477.1.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([O:12][CH3:13])=[C:7]([O:14][CH3:15])[CH:6]=2.[CH:16]1(O)[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[CH:16]1([O:1][C:2]2[CH:3]=[N:4][C:5]3[C:10]([CH:11]=2)=[CH:9][C:8]([O:12][CH3:13])=[C:7]([O:14][CH3:15])[CH:6]=3)[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1
Reactant: OC1CCCCC1
Reactant: COc1cc2cc(O)cnc2cc1OC
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COc1cc2cc(OC3CCCCC3)cnc2cc1OC

Procedure:
To a THF solution (30 mL) at 0° C. is added 3-hydroxy-6,7-dimethoxyquinoline (0.237 g, 1.15 mmole), cyclohexanol (0.347 g, 3.46 mmole), Ph3P (0.908 g, 3.46 mmole). Diethylazodicarboxylate is added portionwise until the solution retained a deep red color (0.663 g, 3.81 mmole). After 4 hours the solution is concentrated and the residue chromatographed (50% EtOAc in hexanes). The product is recrystallized from isopropanol/hexanes as the HCl salt as a white solid (m.p. 229-232° C., dec.).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:13]=[CH:14][CH:15]=1)[O:5][CH:6]1[CH2:9][N:8]([C:10](Cl)=[O:11])[CH2:7]1.[OH-].[NH4+:17]>O1CCCC1.O>[CH3:1][C:2]1[CH:3]=[C:4]([CH:13]=[CH:14][CH:15]=1)[O:5][CH:6]1[CH2:9][N:8]([C:10]([NH2:17])=[O:11])[CH2:7]1
Reactant: [NH4+]
Reactant: Cc1cccc(OC2CN(C(=O)Cl)C2)c1
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: Cc1cccc(OC2CN(C(N)=O)C2)c1
Reaction time: 18 h
Yield: 50 %

Procedure:
A stirred solution of 3.92 g (0.01 mole) of crude (57.59%) 3-(3-methylphenoxy)-1-azetidinecarbonyl chloride in 15 ml of tetrahydrofuran was treated with 1.9 g (2 ml) (0.03 mole) of 57% ammonium hydroxide. After stirring for 18 hr, the reaction mixture was diluted with 200 ml of water. The oil which separated solidified on standing, (3.2 g), and was recrystallized from isopropanol, yielding 1 g (50%) of fine white crystals, m.p. 167°-168° C.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]=[C:9]=[S:10])=[CH:4][CH:3]=1.[C:11]1([N:17]=[C:18]=[O:19])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>C1C=CC=CC=1.C(N(CC)CC)C.C([O-])(=O)CCCCCCCCCCC.C([O-])(=O)CCCCCCCCCCC.C([Sn+2]CCCC)CCC>[C:11]1([NH:17][C:18]([O:1][C:2]2[CH:7]=[CH:6][C:5]([N:8]=[C:9]=[S:10])=[CH:4][CH:3]=2)=[O:19])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: Oc1ccc(N=C=S)cc1
Reactant: O=C=Nc1ccccc1
Agent: CCCCCCCCCCCC(=O)[O-]
Agent: CCCC[Sn+2]CCCC
Solvent: CCN(CC)CC
Solvent: c1ccccc1
Product: O=C(Nc1ccccc1)Oc1ccc(N=C=S)cc1

Procedure:
By a procedure similar to that of Example I, the above compound (5.2 g., m.p. 139°-142° C.) was prepared from 7.6 g. (0.05 m.) of p-hydroxyphenylisothiocyanate and 6.0 g. (0.05 m.) of phenyl isocyanate, using 35 mls. of benzene as a solvent and 2 drops each of triethylamine and dibutyltin dilaurate as catalysts.
Reaction SMILES: [CH2:1]([P:3]([O-:9])[O:4][CH2:5][CH2:6][CH2:7][CH3:8])[CH3:2].N12CCCN=C1CCCCC2.Cl[CH2:22][CH:23]=[C:24]([CH3:26])[CH3:25]>C1C=CC([P]([Ni]([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.C1(C)C=CC=CC=1>[CH2:1]([P:3]([CH2:22][CH:23]=[C:24]([CH3:26])[CH3:25])(=[O:9])[O:4][CH2:5][CH2:6][CH2:7][CH3:8])[CH3:2]
Reactant: CCCCOP([O-])CC
Reactant: CC(C)=CCCl
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Ni]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: C1CCC2=NCCCN2CC1
Product: CCCCOP(=O)(CC)CC=C(C)C
Yield: 75.8 %

Procedure:
At room temperature, a three-neck flask equipped with stirrer and high-performance condenser is initially charged with 400 g of toluene and this initial charge is devolatilized by stirring and passing nitrogen through it. Then, under nitrogen, 6.65 g (6 mmol) of tetrakis(triphenylphosphine)nickel and 30 g (0.2 mol) of butyl ethylphosphonite (produced as in Example 2) and 30.4 g (0.2 mol) of 1,8-diazabicyclo[5.4.0]undec-7-ene are added followed by the dropwise addition of 20.9 g (0.2 mol) of 1-chloro-3-methyl-2-butene. Following a reaction time of 5 hours, the reaction solution is passed for purification through a column charged with Deloxan® THP Hand the solvent is removed in vacuo. The product is purified by column chromatography to obtain 33.1 g (76% of theory) of butyl ethyl(3-methyl-2-butenyl)phosphinate as colorless oil.
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[CH:10][C:9]([Br:12])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[C:13]([C:15]1[CH:25]=[CH:24][C:18]([O:19][CH2:20][C:21](Cl)=[O:22])=[CH:17][CH:16]=1)#[N:14].C(N(CC)CC)C>ClCCl>[Br:12][C:9]1[CH:10]=[CH:11][C:2]([NH:1][C:21](=[O:22])[CH2:20][O:19][C:18]2[CH:24]=[CH:25][C:15]([C:13]#[N:14])=[CH:16][CH:17]=2)=[C:3]([CH:8]=1)[C:4]([O:6][CH3:7])=[O:5]
Reactant: COC(=O)c1cc(Br)ccc1N
Reactant: N#Cc1ccc(OCC(=O)Cl)cc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(=O)c1cc(Br)ccc1NC(=O)COc1ccc(C#N)cc1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
To a solution of methyl 2-amino-5-bromobenzoate (4.0 g, 17.39 mmol) in dichloromethane (60 mL) was added 2-(4-cyanophenoxy)acetyl chloride (3.74 g, 19.13 mmol, Intermediate 2: step a) to form a thick suspension. An additional 30 mL of dichloromethane was added. The reaction was then cooled to 0° C. and triethylamine (5.32 mL, 38.25 mmol) was added dropwise. The cold bath was removed and the reaction was stirred at room temperature for 2 hours, then filtered to give the title compound as a white solid. The filtrate was washed with water, followed by saturated aqueous NH4Cl solution. The organic layer was dried (MgSO4), filtered, concentrated, and the residue was purified by flash column chromatography (silica gel, 20% EtOAc-heptane) to afford more of the title compound.
Reaction SMILES: P(Cl)(Cl)(Cl)=O.[CH3:6][C:7]1[N:8]=[C:9]([CH3:26])[N:10]2[C:15]=1[C:14](=O)[NH:13][C:12]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([N+:23]([O-:25])=[O:24])[CH:18]=1)=[N:11]2.[NH:27]1[CH:31]=[N:30][CH:29]=[N:28]1>N1C=CC=CC=1>[CH3:6][C:7]1[N:8]=[C:9]([CH3:26])[N:10]2[C:15]=1[C:14]([N:27]1[CH:31]=[N:30][CH:29]=[N:28]1)=[N:13][C:12]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([N+:23]([O-:25])=[O:24])[CH:18]=1)=[N:11]2
Reactant: c1nc[nH]n1
Reactant: Cc1nc(C)n2nc(-c3cccc([N+](=O)[O-])c3)[nH]c(=O)c12
Solvent: c1ccncc1
Solvent: O=P(Cl)(Cl)Cl
Product: Cc1nc(C)n2nc(-c3cccc([N+](=O)[O-])c3)nc(-n3cncn3)c12
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
2.35 g (15.35 mmol) of phosphoryl chloride are added dropwise under argon to a solution of 1.46 g (5.12 mmol) of 5,7-dimethyl-2-(3-nitrophenyl)imidazo-[5,1-f][1,2,4]triazin-4-(3H)one from example 9A in 50 ml of dry pyridine at 0° C. and the mixture is stirred for 30 min at RT. Subsequently, 3.18 g (46.06 mmol) of 1,2,4-triazole are added, and the mixture is stirred for 3 h at 20° C. The reaction mixture is concentrated, the residue is treated with aqueous sodium hydrogencarbonate solution and the mixture is extracted with dichloromethane. The organic phase is dried (sodium sulfate) and the solvent is removed in vacuo. The residue is purified by flash chromatography (eluent: dichloromethane/methanol 100:1).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[C:5]#[N:6].[I:10]Cl.O>C(O)(=O)C>[OH:1][C:2]1[CH:9]=[CH:8][C:7]([I:10])=[C:4]([CH:3]=1)[C:5]#[N:6]
Reactant: N#Cc1cccc(O)c1
Reactant: ClI
Solvent: O
Solvent: CC(=O)O
Product: N#Cc1cc(O)ccc1I
Yield: 6.5 %

Procedure:
3-Hydroxy-benzonitrile (15 g, 0.126 mol) and iodine monochloride (28 g, 0.172 mol) is heated in acetic acid for 15 hours at 45° C. H2O is added to precipitate the product out. After the precipitate is collected and washed with Na2SO3, the residue is chromatographed with chloroform to get the product (2 g, 7%). MS (ESI): 244.0 (M−1)−1.
Reaction SMILES: [Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1OS(C(F)(F)F)(=O)=O.[N:27]1[CH:32]=[CH:31][C:30]([CH:33]([NH2:35])[CH3:34])=[CH:29][CH:28]=1>>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1[NH:35][CH:33]([C:30]1[CH:31]=[CH:32][N:27]=[CH:28][CH:29]=1)[CH3:34]
Reactant: CC(N)c1ccncc1
Reactant: O=C(N1CCc2ccc(Cl)c(OS(=O)(=O)C(F)(F)F)c2CC1)C(F)(F)F
Product: CC(Nc1c(Cl)ccc2c1CCN(C(=O)C(F)(F)F)CC2)c1ccncc1

Procedure:
Use a method similar to the General Procedure 5-3 to couple 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (400 mg, 0.94 mmol) and (±)-1-pyridin-4-yl-ethylamine (prepared as described in Bull. Kor. Chem. Soc. 1998, 19 (8), 891-893) (172 mg, 1.41 mmol). Purify by chromatography on silica gel eluting with hexane/EtOAc (1:0, 4:1 and 1:1) to give (±)-7-chloro-6-[(1-pyridin-4-yl-ethyl)-amino]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine.
Reaction SMILES: [CH2:1]1[CH:5]2[CH:6]3C=CC([CH:4]2[CH:3]=[CH:2]1)C3.C[SiH:12]([Cl:14])[Cl:13].CCCCCCCCCCCCCCCC>[Pd].C(P(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[CH:5]1([CH2:6][SiH:12]([Cl:14])[Cl:13])[CH2:4][CH2:3][CH:2]=[CH:1]1
Reactant: C1=CC2C3C=CC(C3)C2C1
Reactant: C[SiH](Cl)Cl
Agent: [Pd]
Agent: CCCCP(CCCC)CCCC
Solvent: CCCCCCCCCCCCCCCC
Solvent: Cc1ccccc1
Product: Cl[SiH](Cl)CC1C=CCC1
Reaction time: 1 h
Yield: 319.8 %

Procedure:
As described in Example 2, 2.92 g (0.0221 mol) of dicyclopentadiene, 3.79 g (0.0331 mol) of methyldichlorosilane, 0.0602 g 1% Pd on Charcoal, 86 μL (0.000267 mol) of tributylphosphine and 4 mL of toluene and 2 mL of hexadecane were placed in a reactor. The reactor was sealed and the reaction was performed at 180° C. for 1 hour. Products were subject to simple vacuum distillation, thereby providing a mixture (12.8 g) of (2-cyclopentenyl)methyldichlorosilane (3.8 g, 63%), other unreacted reactants, toluene, hexadecane, and unidentified compounds. Besides, tetrakis(triphenylphosphine)palladium also showed catalyst effect.