Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:3]1[C:8]([C:9]2[CH:14]=[CH:13][C:12]([S:15]([CH2:18][CH3:19])(=[O:17])=[O:16])=[CH:11][C:10]=2[O:20][CH3:21])=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1)#[N:2].Cl[C:26]1[C:27]2[N:34]=[CH:33][N:32]([CH2:35][CH3:36])[C:28]=2[N:29]=[N:30][CH:31]=1>>[CH2:35]([N:32]1[C:28]2[N:29]=[N:30][CH:31]=[C:26]([C:6]3[CH:7]=[C:8]([C:9]4[CH:14]=[CH:13][C:12]([S:15]([CH2:18][CH3:19])(=[O:17])=[O:16])=[CH:11][C:10]=4[O:20][CH3:21])[C:3]([C:1]#[N:2])=[CH:4][CH:5]=3)[C:27]=2[N:34]=[CH:33]1)[CH3:36]
Reactant: CCS(=O)(=O)c1ccc(-c2cc(B(O)O)ccc2C#N)c(OC)c1
Reactant: CCn1cnc2c(Cl)cnnc21
Product: CCn1cnc2c(-c3ccc(C#N)c(-c4ccc(S(=O)(=O)CC)cc4OC)c3)cnnc21
Yield: 10 %

Procedure:
Prepared according to the method described for Example 45 using (6-cyano-4′-(ethylsulfonyl)-2′-methoxy-[1,1-biphenyl]-3-yl)boronic acid (Preparation 67) and 4-chloro-7-ethyl-7H-imidazo[4,5-c]pyridazine (Preparation 8) to afford the title compound as a white solid in 10% yield, 10.1 mg.
Reaction SMILES: [C-:1]#[N:2].[K+].CS(O[CH2:9][CH2:10][C:11]([C:25]1[CH:34]=[CH:33][C:28]2[O:29][CH2:30][CH2:31][O:32][C:27]=2[CH:26]=1)([C:13]1[C:21]2[C:16](=[C:17]([CH2:22][S:23][CH3:24])[CH:18]=[CH:19][CH:20]=2)[NH:15][CH:14]=1)[CH3:12])(=O)=O.C(OCC)(=O)C>CS(C)=O>[O:29]1[C:28]2[CH:33]=[CH:34][C:25]([C:11]([C:13]3[C:21]4[C:16](=[C:17]([CH2:22][S:23][CH3:24])[CH:18]=[CH:19][CH:20]=4)[NH:15][CH:14]=3)([CH3:12])[CH2:10][CH2:9][C:1]#[N:2])=[CH:26][C:27]=2[O:32][CH2:31][CH2:30]1
Reactant: [C-]#N
Reactant: CSCc1cccc2c(C(C)(CCOS(C)(=O)=O)c3ccc4c(c3)OCCO4)c[nH]c12
Agent: [K+]
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: CSCc1cccc2c(C(C)(CCC#N)c3ccc4c(c3)OCCO4)c[nH]c12
Temperature: 80 °C
Reaction time: 16 h

Procedure:
150 mg (2.30 mmol) of potassium cyanide were added to 530 mg (1.15 mmol) of the compound from Example 117A in 10 ml of DMSO. The mixture was stirred at 80° C. for 16 h, ethyl acetate was added to the reaction solution, and the mixture was washed twice with water and once with saturated aqueous sodium chloride solution. The combined organic phases were freed of solvent, and the crude product was purified by preparative HPLC (mobile phase: acetonitrile/water gradient). 328 mg (73% of theory) of the target compound were obtained.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH:7]=O)[CH:2]=1.[NH2:9][NH:10][C:11]([NH:13][NH2:14])=[O:12]>CO>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH:7]=[N:9][NH:10][C:11]([NH:13][N:14]=[CH:7][C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)=[O:12])[CH:2]=1
Reactant: O=Cc1cccnc1
Reactant: NNC(=O)NN
Solvent: CO
Product: O=C(NN=Cc1cccnc1)NN=Cc1cccnc1
Reaction time: 1 h

Procedure:
32.2 g of pyridine-3-carbaldehyde are added in the course of approx. 10 minutes, at room temperature, to a suspension of 13.5 g of carbohydrazide in 200 ml of methanol, the temperature rising to more than 35°. The reaction mixture is further stirred for 1 hour and then cooled to 5°. The crystals that precipitate are filtered off with suction and dried in vacuo at 70°. 40 g of the title compound having a melting point of 202°-204° are thus obtained.
Reaction SMILES: Br[CH2:2][C:3]1[NH:8][C:7]([C:9]2[S:10][CH:11]=[CH:12][N:13]=2)=[N:6][CH:5]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=2[Cl:21])[C:4]=1[C:22]([O:24][CH2:25][CH3:26])=[O:23].[NH:27]1[CH2:32][CH2:31][O:30][C@H:29]([CH2:33][OH:34])[CH2:28]1>>[Cl:21][C:15]1[CH:16]=[C:17]([Cl:20])[CH:18]=[CH:19][C:14]=1[CH:5]1[C:4]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[C:3]([CH2:2][N:27]2[CH2:32][CH2:31][O:30][C@H:29]([CH2:33][OH:34])[CH2:28]2)[NH:8][C:7]([C:9]2[S:10][CH:11]=[CH:12][N:13]=2)=[N:6]1
Reactant: OC[C@@H]1CNCCO1
Reactant: CCOC(=O)C1=C(CBr)NC(c2nccs2)=NC1c1ccc(Cl)cc1Cl
Product: CCOC(=O)C1=C(CN2CCO[C@H](CO)C2)NC(c2nccs2)=NC1c1ccc(Cl)cc1Cl
Yield: 33.2 %

Procedure:
Ethyl 6-(bromomethyl)-4-(2,4-dichlorophenyl)-2-(thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate (0.95 g, 2 mmol) was reacted with (S)-morpholin-2-ylmethanol (0.34 g, 2.2 mmol) according to the procedure as described in Example 25, Step B to give the title compound as a yellow solid (0.34 g, 33%). The compound was characterized by the following spectroscopic data:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:15]=[C:16]([Cl:19])[C:17]=1[OH:18])[C:5]([NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[OH:14])=[O:6].[C:20](Cl)(=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.Cl>N1C=CC=CC=1>[C:20]([O:14][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=1[NH:7][C:5](=[O:6])[C:4]1[CH:3]=[C:2]([Cl:1])[C:17]([O:18][C:5](=[O:6])[C:4]2[CH:15]=[CH:16][CH:17]=[CH:2][CH:3]=2)=[C:16]([Cl:19])[CH:15]=1)(=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: O=C(Nc1ccccc1O)c1cc(Cl)c(O)c(Cl)c1
Reactant: O=C(Cl)c1ccccc1
Agent: Cl
Solvent: c1ccncc1
Product: O=C(Nc1ccccc1OC(=O)c1ccccc1)c1cc(Cl)c(OC(=O)c2ccccc2)c(Cl)c1
Yield: 88.2 %

Procedure:
3,5-Dichloro-2',4-dihydroxybenzanilide (1 g.) was dissolved in dry pyridine (15 ml.) in the cold at 0°-5° C. and to it was added dropwise benzoyl chloride (1.2 ml.). With gently stirring reaction was continued for several hours. The solution was then poured into ice-cold water and acidified with 1 N hydrochloric acid to pH 2, yielding oily material which was extracted by ethyl acetate. The ethyl acetate solution was washed with 1 N hydrochloric acid and 5% sodium bicarbonate solution in that order and dried with anhydrous sodium sulfate, followed by removal of the solvent by evaporation. The residue was subjected to recrystallization from ether and petroleum ether mixture to give white crystals (1.5 g.) of 2',4-dibenzoyloxy-3,5-dichlorobenzanilide. Yield: 88.2%. Melting point: 157°-160° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[CH:9]([CH3:25])[C:10]([C:16]1[CH:17]=[C:18]([CH3:24])[C:19](=[O:23])[N:20]([CH3:22])[CH:21]=1)([OH:15])[C:11]([F:14])([F:13])[F:12].F[C:27]1[CH:34]=[CH:33][C:30]([CH:31]=[O:32])=[C:29]([C:35]([F:38])([F:37])[F:36])[CH:28]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C)C(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([CH:5]=[CH:4][C:3]=1[CH:9]([CH3:25])[C:10]([C:16]1[CH:17]=[C:18]([CH3:24])[C:19](=[O:23])[N:20]([CH3:22])[CH:21]=1)([OH:15])[C:11]([F:13])([F:14])[F:12])[O:8][C:27]1[CH:34]=[CH:33][C:30]([CH:31]=[O:32])=[C:29]([C:35]([F:36])([F:38])[F:37])[CH:28]=1
Reactant: Cc1cc(C(O)(C(C)c2ccc(O)cc2Cl)C(F)(F)F)cn(C)c1=O
Reactant: O=Cc1ccc(F)cc1C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CC(=O)N(C)C
Product: Cc1cc(C(O)(C(C)c2ccc(Oc3ccc(C=O)c(C(F)(F)F)c3)cc2Cl)C(F)(F)F)cn(C)c1=O
Temperature: 25 °C
Reaction time: 3 h
Yield: 95.2 %

Procedure:
To a stirred solution of 5-[2-(2-chloro-4-hydroxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-1,3-dimethyl-1H-pyridin-2-one (Example 203, step 5, 80 mg) in N,N-dimethylacetamide (1.5 ml) were added 4-fluoro-2-(trifluormethyl)benzaldehyde (63 mg) and cesium carbonate (208 mg). The mixture was stirred at room temperature for 3 h. Water was added and the mixture was extracted with ethyl acetate. The organic phase was dried (MgSO4), filtered and concentrated. The product was purified by chromatography (SiO2, cyclohexane/EtOAc 1:0=>0:1) to give the title compound (111 mg) as an off-white solid. MS (m/e)=548.2 [M+H+].
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]2([OH:16])[CH2:13][CH2:12][NH:11][CH2:10][C:9]2([CH3:15])[CH3:14])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:24][CH2:25][CH:26]=[C:27]1[C:33]2[CH:34]=[CH:35][CH:36]=[N:37][C:32]=2[CH2:31][O:30][C:29]2[CH:38]=[CH:39][C:40]([C:42](=[O:44])[CH3:43])=[CH:41][C:28]1=2>C(#N)C.O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]2([OH:16])[CH2:13][CH2:12][N:11]([CH2:24][CH2:25][CH:26]=[C:27]3[C:33]4[CH:34]=[CH:35][CH:36]=[N:37][C:32]=4[CH2:31][O:30][C:29]4[CH:38]=[CH:39][C:40]([C:42](=[O:44])[CH3:43])=[CH:41][C:28]3=4)[CH2:10][C:9]2([CH3:14])[CH3:15])=[CH:4][CH:3]=1
Reactant: CC(=O)c1ccc2c(c1)C(=CCCBr)c1cccnc1CO2
Reactant: CC1(C)CNCC[C@]1(O)c1ccc(Cl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: O
Product: CC(=O)c1ccc2c(c1)C(=CCCN1CC[C@](O)(c3ccc(Cl)cc3)C(C)(C)C1)c1cccnc1CO2
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a suspension of the (S)-4-(4-chloro-phenyl)-3,3-dimethyl-piperidin-4-ol (5.50 g, 22.94 mmol) in acetonitrile (200 mL) and water (50 mL) was added potassium carbonate (7.17 g, 51.9 mmol) followed by solid 1-[5-(3-bromo-propylidene)-5,11-dihydro-10-oxa-1-aza-dibenzo[a,d]cyclohepten-7-yl]-ethanone (6.30 g, 17.3 mmol). The heterogeneous mixture was stirred at room temperature 4 hours, warmed to 50° C. and stirred 13 hours. The mixture was cooled to room temperature and acetonitrile was removed under reduced pressure. The aqueous layer was extracted with ethyl acetate (750 mL) and the extract was washed with brine, dried over sodium sulfate, filtered and concentrated. The crude residue was purified by silica gel chromatography (3:1 ethyl acetate:hexanes) to afford (S)-1-(5-{3-[4-(4-Chloro-phenyl)-4-hydroxy-3,3-dimethyl-piperidin-1-yl]-propylidene}-5,11-dihydro-10-oxa-1-aza-dibenzo[a,d]cyclohepten-7-yl)-ethanone as an off-white solid.
Reaction SMILES: CO[C:3]([C:5]1[C:6]([OH:31])=[C:7]2[C:12](=[CH:13][N:14]=1)[N:11](CC1C=CC=CC=1)[C:10](=[O:22])[C:9]([C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=1)=[CH:8]2)=[O:4].[NH2:32][CH2:33][CH2:34][C:35]([OH:37])=[O:36].C[O-].[Na+]>>[CH2:9]([N:14]1[CH:13]=[C:12]2[C:7](=[CH:8][CH:9]([C:23]3[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=3)[C:10](=[O:22])[NH:11]2)[C:6]([OH:31])=[C:5]1[C:3]([NH:32][CH2:33][CH2:34][C:35]([OH:37])=[O:36])=[O:4])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: NCCC(=O)O
Reactant: COC(=O)c1ncc2c(cc(-c3ccc(OC)cc3)c(=O)n2Cc2ccccc2)c1O
Agent: C[O-]
Agent: [Na+]
Product: COc1ccc(C2C=C3C(=CN(Cc4ccccc4)C(C(=O)NCCC(=O)O)=C3O)NC2=O)cc1
Temperature: 25 °C
Yield: 146 %

Procedure:
A mixture of 1-benzyl-5-hydroxy-3-(4-methoxy-phenyl)-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (30 mg, 0.072 mmol), β-alanine (854 mg, 9.6 mmol) and NaOMe solution (14.4 mL, 7.2 mmol, 0.5 M in MeOH) was refluxed for 16 h. After the mixture was cooled to r.t., the solvent was evaporated in vacuo. The residue was dissolved in saturated NaHCO3 and washed several times with ether. The aqueous layer was acidified to pH about 2 with 6 M HCl, and the resulting precipitate was isolated by filtration to give 25 mg of the title compound. MS: (+) m/z 474.30 (M+1).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([OH:16])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[NH2:50][C:51]1[CH:52]=[C:53]([CH:56]=[CH:57][C:58]=1[NH2:59])[C:54]#[N:55]>CN(C=O)C.CN(C1C=CN=CC=1)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([C:14](=[O:16])[NH:59][C:58]2[CH:57]=[CH:56][C:53]([C:54]#[N:55])=[CH:52][C:51]=2[NH2:50])[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(C)(C)OC(=O)N1CCC(C(=O)O)CC1
Reactant: N#Cc1ccc(N)c(N)c1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: CN(C)c1ccncc1
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)N1CCC(C(=O)Nc2ccc(C#N)cc2N)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of piperidine-1,4-dicarboxylic acid mono-tert-butyl ester (14.1 g, 0.061 mol) in DMF (282 mL) was added HBTU (27.76 g, 0.073 mol), DMAP (10.2 g, 0.084 mol) and diisopropylethyl amine (24.2 mL). The reaction mixture was stirred for 30 minutes at rt before 3,4-diaminobenzonitrile (8 g, 0.059 mol) was added. The mixture was stirred overnight at rt before the reaction was quenched by pouring into water (2 L). The mixture was extracted with CH2Cl2 and the organic phase washed successively with 1M aq. HCl solution and 10% aq. Na2CO3 solution, dried (Na2SO4) and concentrated in vacuo. Purification by chromatography on silica gel afforded the title compound.
Reaction SMILES: COC1[CH:12]=[CH:11][C:6]2[CH:7]=[C:8]([CH3:10])[O:9][C:5]=2C=1.B(Br)(Br)Br.C(N(CC)CC)C.[C:24]([O:27][C:28](=O)[CH3:29])(=[O:26])[CH3:25]>ClCCl>[CH3:10][C:8]1[O:9][C:5]2[CH:29]=[C:28]([O:27][C:24](=[O:26])[CH3:25])[CH:12]=[CH:11][C:6]=2[CH:7]=1
Reactant: CC(=O)OC(C)=O
Reactant: COc1ccc2cc(C)oc2c1
Agent: BrB(Br)Br
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)Oc1ccc2cc(C)oc2c1
Temperature: 0 °C
Reaction time: 1 h
Yield: 65.4 %

Procedure:
A solution of 6-methoxy-2-methyl-benzofuran (17.4 g, 107 mmol) in dichloromethane (200 mL) at 0° C. is treated with boron tribromide (1.0 M, 107 mL). The mixture is stirred at 0° C. for 60 minutes and quenched with water (50 mL). The organic layer is dried over Na2SO4, filtered, and concentrated. The crude product is purified by flash chromatography eluted with 25% EtOAc/Hexanes, and the appropriate fractions are concentrated. The material is dissolved in dichloromethane (150 mL) and triethylamine (17.0 mL, 122 mmol) at 0° C. is treated with acetic acid anhydride (7.22 mL, 76.35 mmol). The reaction is stirred for 16 hours and allowed to warm to room temperature. The reaction is quenched with MeOH (10 mL) and concentrated. The residue is purified by silica gel chromatography with 25% EtOAc/Hexanes to provide acetic acid 2-methyl-benzofuran-6-yl ester (9.50 g, 82%). 1H NMR (400 MHz, CDCl3): δ 7.40-7.38 (d, 1H), 7.15 (s, 1H), 6.91-6.88 (d, 1H), 6.32 (s, 1H), 2.41 (s, 3H), 2.29 (s, 3H).
Reaction SMILES: I[C:2]1[CH:11]=[C:10]2[C:5]([C:6]([N:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)=[CH:7][C:8]([CH3:12])=[N:9]2)=[CH:4][CH:3]=1.[C-:18]#[N:19].[K+]>C(#N)C.C(OCC)(=O)C.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.[Cu](I)I>[CH3:12][C:8]1[CH:7]=[C:6]([N:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)[C:5]2[C:10](=[CH:11][C:2]([C:18]#[N:19])=[CH:3][CH:4]=2)[N:9]=1
Reactant: [C-]#N
Reactant: Cc1cc(N2CCCC2)c2ccc(I)cc2n1
Agent: I[Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CC#N
Product: Cc1cc(N2CCCC2)c2ccc(C#N)cc2n1
Yield: 75.2 %

Procedure:
A suspension of 7-iodo-2-methyl-4-pyrrolidin-1-yl-quinoline (1.50 g, 4.43 mmol), potassium cyanide (578 mg, 8.87 mmol), tetrakis(triphenylphosphine)palladium(0) (256 mg, 0.22 mmol), and copper iodide (85 mg, 0.44 mmol) in acetonitrile (10 mL) was refluxed for 90 min. After cooling the mixture was diluted with ethyl acetate, filtered, and the filtrate was washed with brine, dried (Na2SO4), and evaporated. Chromatography (SiO2, dichloromethane/methanol 19:1) yielded the title compound (791 mg, 75%). Light brown solid, ISP-MS: m/e=238.3 ([M+H]+).
Reaction SMILES: CS(O[C@@H:6]1[CH2:11][CH2:10][O:9][CH2:8][C@H:7]1[NH:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])(=O)=O.[N-:20]=[N+:21]=[N-:22].[Na+].C([O-])(=O)C.[Na+]>CN(C=O)C>[N:20]([C@H:6]1[CH2:11][CH2:10][O:9][CH2:8][C@H:7]1[NH:12][C:13](=[O:14])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[N+:21]=[N-:22]
Reactant: [N-]=[N+]=[N-]
Reactant: CC(C)(C)OC(=O)N[C@@H]1COCC[C@H]1OS(C)(=O)=O
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N[C@@H]1COCC[C@@H]1N=[N+]=[N-]
Temperature: 95 °C
Yield: 99.7 %

Procedure:
(3R,4R)-3-((tert-butoxycarbonyl)amino)tetrahydro-2H-pyran-4-yl methanesulfonate (2.2 g, 7.45 mmol), sodium azide (0.968 g, 14.90 mmol) and sodium acetate (1.222 g, 14.90 mmol) were taken up in DMF (15 ml). The reaction mixture was heated to 95° C. overnight. The reaction mixture was removed from heat and 20 ml of water was added and stirred while cooling. The reaction mixture was extracted with EtOAc. The organic layers were combined and washed with water. The organics were dried and solvent removed to give tert-butyl ((3S,4S)-4-azidotetrahydro-2H-pyran-3-yl)carbamate (1.8 g, 7.43 mmol, 100% yield) as a yellow oil. MS (ES+) C10H18N4O3 requires: 242, found: 265 [M+Na]+.
Reaction SMILES: [Br:1][C:2]1[C:7](=[O:8])[N:6]([C:9]2[C:14]([F:15])=[CH:13][CH:12]=[CH:11][C:10]=2[F:16])[C:5]([CH:17]=O)=[CH:4][C:3]=1[O:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:22]=1[F:28].[CH3:29][O:30][CH2:31][CH2:32][NH2:33]>ClCCl>[Br:1][C:2]1[C:7](=[O:8])[N:6]([C:9]2[C:14]([F:15])=[CH:13][CH:12]=[CH:11][C:10]=2[F:16])[C:5]([CH2:17][NH:33][CH2:32][CH2:31][O:30][CH3:29])=[CH:4][C:3]=1[O:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:22]=1[F:28]
Reactant: COCCN
Reactant: O=Cc1cc(OCc2ccc(F)cc2F)c(Br)c(=O)n1-c1c(F)cccc1F
Solvent: ClCCl
Product: COCCNCc1cc(OCc2ccc(F)cc2F)c(Br)c(=O)n1-c1c(F)cccc1F
Yield: 36 %

Procedure:
The title compound was prepared by reacting 5-bromo-4-[(2,4-difluorobenzyl)oxy]-1-(2,6-difluorophenyl)-6-oxo-1,6-dihydropyridine-2-carbaldehyde-(0.319 g, 0.7 mmol) with 2-methoxy ethylamine (0.086 ml, 1.0 mmol) and triacetoxy sodium borohydride (0.42 g, 2.0 mmol) in dichloromethane (4 mL)by using a procedure, similar to the one described for Example 468. The crude product was purified by flash column chromatography. Elution with (50:50→100) hexanes-ethyl acetate to give 0.13 g of the desired product.
Reaction SMILES: [OH2:1].[C:2]([OH:5])(=O)[CH3:3]>>[O:1]=[CH:3][C@@H:2]([C@H:3]([C@@H:2]([C@@H:3]([CH2:2][OH:5])[OH:1])[OH:5])[OH:1])[OH:5]
Reactant: CC(=O)O
Reactant: O
Product: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO

Procedure:
The single bath process according to the invention was formed by adding 28 liters of water to the machine at 100° F., and subsequently raising and controlling the temperature of the bath by means of the integrated heating element to a temperature in the range of 135°-138° F. To the water was added 7 grams (0.25 grams/liter of bath) of a conventional non-ionic detergent which acts as a wetting agent and 14 grams (0.5 grams/liter of bath) of 56% acetic acid to adjust the pH to 4.5-5.5. Subsequently was added cellulase enzymes commercially available as "BACTOSOL® CA" (a cellulase enzyme containing preparation that hydrolyses cellulose to produce glucose and glucose polymers, available from Sandoz Chemical Inc., Charlotte, N.C.) which was indicated by the manufacturer to be optimally active at a temperature of approximately 130°-150° F., at a pH in the range of 3.8-5.5. Present in the machine was a cellulase enzyme concentration of 2940 CMC units per lb. of denim. Afterwards was added 560 grams (20 grams/liter of bath) of Glauber's salt and 1% by weight (based on the dry denim textile) of a direct dye solution Lumicrease® Orange 3LG (Colour Index Direct Orange 107) (available from Sandoz Chemical Inc.) which was prepared from a dry form according to the manufacturer's instructions. The machine was operated at the "wash" setting for 45 minutes, after which the liquid was removed from the machine. The treated denim was observed to have been effectively overdyed. It was also observed that good exhaustion of the dye was achieved by visual inspection of a sample of the liquid as it was removed from the machine.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2(O)[C:14]3[CH:15]=[CH:16][S:17][C:13]=3[CH2:12][CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].C([SiH](CC)CC)C.FC(F)(F)C(O)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]2[C:14]3[CH:15]=[CH:16][S:17][C:13]=3[CH2:12][CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: OC1(c2ccc(Cl)c(Cl)c2)CCCc2sccc21
Agent: CC[SiH](CC)CC
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Clc1ccc(C2CCCc3sccc32)cc1Cl
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 76.5 %

Procedure:
To a stirring solution of 4-(3,4-dichlorophenyl)-4,5,6,7-tetrahydro-1-benzothiophene-4-ol (4.50 g, 15.0 mmol) in methylene chloride (75 mL) were added triethylsilane (11 mL, 69 mmol) and trifluoroacetic acid (12.0 mL, 156 mmol). The solution became reddish orange but no exotherm was observed. The reaction was stirred for 2.5 hr at rt under an atmosphere of nitrogen. The resulting somewhat fluorescent reddish orange solution was concentrated on the rotovap. Ethyl acetate and water were added (˜100 ml each), the mixture was stirred, and a saturated solution of NaHCO3 was slowly added until the mixture became basic. The mixture was transferred to a separatory funnel, the organic layer was separated, and the aqueous layer was extracted again with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated to leave crude product as a light brown oil. The residue was purified using column chromatography on silica gel (80 g RediSep column, eluant 100% hexane) give the product (3.25 g, 76% yield) as a clear oil. LCMS: (FA) product did not give an ionization peak. 1H NMR (400 MHz, DMSO) δ 7.59-7.50 (d, J=8.3 Hz, 1H), 7.37-7.31 (d, J=2.1 Hz, 1H), 7.26-7.19 (d, J=5.2 Hz, 1H), 7.12-7.01 (dd, J=8.3, 2.1 Hz, 1H), 6.48-6.40 (d, J=5.2 Hz, 1H), 4.11-4.00 (t, J=6.2 Hz, 1H), 2.91-2.71 (m, 2H), 2.14-2.00 (m, 1H), 1.91-1.62 (m, 3H).
Reaction SMILES: [Si:1]([O:18][CH2:19][CH2:20][C:21]1[C:22](=[O:38])[N:23]([C:27]2[C:32]([CH3:33])=[CH:31][C:30]([N+:34]([O-])=O)=[CH:29][C:28]=2[CH3:37])[CH:24]=[CH:25][CH:26]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>O1CCCC1>[NH2:34][C:30]1[CH:31]=[C:32]([CH3:33])[C:27]([N:23]2[CH:24]=[CH:25][CH:26]=[C:21]([CH2:20][CH2:19][O:18][Si:1]([C:14]([CH3:15])([CH3:16])[CH3:17])([C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=3)[C:22]2=[O:38])=[C:28]([CH3:37])[CH:29]=1
Reactant: Cc1cc([N+](=O)[O-])cc(C)c1-n1cccc(CCO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)c1=O
Solvent: C1CCOC1
Product: Cc1cc(N)cc(C)c1-n1cccc(CCO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)c1=O

Procedure:
143 g (271 mmol) of the compound from Example 62A (alternative synthesis) are dissolved in 1.43 l of tetrahydrofuran and flushed with argon. 17 g of palladium on carbon (50%, moistened with water) are added, and the mixture is then hydrogenated at RT in a hydrogen atmosphere under atmospheric pressure. The mixture is then filtered through kieselguhr, the filter cake is washed with tetrahydrofuran and the filtrate is freed from the solvent. The reaction product (134 g) is reacted further without further purification.
Reaction SMILES: [C:1]1([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:6]=[CH:5][C:4]([C:7]([O:12][CH2:13][CH3:14])([CH3:11])[C:8]([OH:10])=O)=[CH:3][CH:2]=1.[NH2:21][CH2:22][C:23]1[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][CH:24]=1>>[C:1]1([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:6]=[CH:5][C:4]([C:7]([O:12][CH2:13][CH3:14])([CH3:11])[C:8]([NH:28][CH2:27][C:26]2[CH:29]=[CH:30][C:23]([C:22]#[N:21])=[CH:24][CH:25]=2)=[O:10])=[CH:3][CH:2]=1
Reactant: CCOC(C)(C(=O)O)c1ccc(-c2ccccc2)cc1
Reactant: N#Cc1ccc(CN)cc1
Product: CCOC(C)(C(=O)NCc1ccc(C#N)cc1)c1ccc(-c2ccccc2)cc1

Procedure:
(RS)-2-Biphenyl-4-yl-2-ethoxy-propionic acid was coupled with 4-aminomethyl benzonitrile to give (RS)-2-biphenyl-4-yl-N-(4-cyano-benzyl)-2-ethoxy-propionamide according to general procedure C. Colorless solid. MS 385.1 ([M+H]+)