Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[S:16][CH:17]=[CH:18][CH:19]=2)=[CH:11][C:10]=1[NH:20][C:21]([C:23]1[CH:33]=[CH:32][C:26]([CH2:27][P:28]([CH3:31])(=[O:30])[OH:29])=[CH:25][CH:24]=1)=[O:22])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:34]1(O)[CH2:37][CH2:36][CH2:35]1.CCN(C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C>[CH:34]1([O:30][P:28]([CH2:27][C:26]2[CH:25]=[CH:24][C:23]([C:21](=[O:22])[NH:20][C:10]3[CH:11]=[C:12]([C:15]4[S:16][CH:17]=[CH:18][CH:19]=4)[CH:13]=[CH:14][C:9]=3[NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])=[CH:33][CH:32]=2)([CH3:31])=[O:29])[CH2:37][CH2:36][CH2:35]1
Reactant: OC1CCC1
Reactant: CC(C)(C)OC(=O)Nc1ccc(-c2cccs2)cc1NC(=O)c1ccc(CP(C)(=O)O)cc1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
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)Nc1ccc(-c2cccs2)cc1NC(=O)c1ccc(CP(C)(=O)OC2CCC2)cc1
Reaction time: 18 h

Procedure:
To a solution of [4-(2-tert-butoxycarbonylamino-5-thiophen-2-yl-phenylcarbamoyl)-benzyl]-methyl-phosphinic acid (57 mg, 0.117 mmol), cyclobutanol (0.038 mL, 0.703 mmol), and Hunig's Base (0.031 mL, 0.176 mmol) in DMF (2 mL) was added BOP (78 mg, 0.176 mmol). After 18 h, the reaction was purified by preparative HPLC Reverse phase (C-18), eluting with acetonitrile/water plus 0.025% TFA (40-100%) to give material after extraction of fractions with EtOAc. 1H NMR (DMSO-d6) δ 9.88 (s, 1H), 8.74 (br s, 1H), 7.90 (d, J=7.6 Hz, 2H), 7.79 (br s, 1H), 7.58 (d, J=8.5 Hz, 1H), 7.52-7.47 (m, 2H), 7.44-7.39 (m, 3H), 7.12-7.09 (m, 1H), 4.64 (m, 1H), 3.27 (dd, J=23.2, 17.6 Hz, 1H), 3.25 (dd, J=23.2, 17.6 Hz, 1H), 2.25-21.4 (m, 2H), 2.05-1.94 (m, 2H), 1.67-1.60 (m, 1H), 1.49-1.42 (m, 1H), 1.43 (s, 9H), 1.31 (d, J=14.1 Hz, 3H). MS: cal'd 441 (MH+; -Boc), exp 441 (MH+; -Boc).
Reaction SMILES: [CH2:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:35])[CH2:15][NH:16][C:17]([C:19]2[CH:23]=[C:22]([O:24][CH2:25][C:26](O)=[O:27])[N:21]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[N:20]=2)=[O:18])[CH2:10][CH2:9]1)=[O:7])[CH2:2][CH2:3][CH3:4].FC1C(O)=C(F)C(F)=C(F)C=1F.[CH:48]1([NH:52][C:53]([C@@H:55]2[CH2:59][C@@H:58]([OH:60])[CH2:57][NH:56]2)=[O:54])[CH2:51][CH2:50][CH2:49]1.C(N1CCOCC1)C>CN(C=O)C.C(Cl)Cl.C(Cl)CCl>[CH2:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([C:14](=[O:35])[CH2:15][NH:16][C:17]([C:19]2[CH:23]=[C:22]([O:24][CH2:25][C:26]([N:56]3[CH2:57][C@H:58]([OH:60])[CH2:59][C@H:55]3[C:53](=[O:54])[NH:52][CH:48]3[CH2:51][CH2:50][CH2:49]3)=[O:27])[N:21]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[N:20]=2)=[O:18])[CH2:12][CH2:13]1)=[O:7])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCOC(=O)N1CCN(C(=O)CNC(=O)c2cc(OCC(=O)O)n(-c3ccccc3)n2)CC1
Reactant: O=C(NC1CCC1)[C@@H]1C[C@@H](O)CN1
Agent: CCN1CCOCC1
Agent: Oc1c(F)c(F)c(F)c(F)c1F
Solvent: CN(C)C=O
Solvent: ClCCl
Solvent: ClCCCl
Product: CCCCOC(=O)N1CCN(C(=O)CNC(=O)c2cc(OCC(=O)N3C[C@H](O)C[C@H]3C(=O)NC3CCC3)n(-c3ccccc3)n2)CC1

Procedure:
To a solution of 700 mg 4-{2-[(5-Carboxymethoxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-acetyl}-piperazine-1-carboxylic acid butyl ester in 10 ml DMF were added 317 mg pentafluorophenol and 330 mg EDC. The mixture was stirred under exclusion of moisture until LCMS indicated complete conversion to the corresponding pentafluorophenolester. (2S,4R)-4-Hydroxy-pyrrolidine-2-carboxylic acid cyclobutylamide hydrotrifluoroacetate (455 mg) was mixed with 0.55 ml N-ethylmorpholine and 5 ml DMF and this mixture added dropwise to the solution of the pentafluorophenolester. After 12 h the reaction mixture was diluted with DCM and washed with aqueous LiCl (4%), saturated aqueous NaHCO3 and brine. The crude product obtained after evaporation of the solvent was purified by preparative HPLC (C18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA). The fractions containing the product were immediately lyophilized to yield the pure product which was taken up in dichloromethane and washed once with aqueous NaHCO3. The residue obtained after evaporation of the solvent was lyophilized again to give the title compound. Yield: 454 mg MS (ES+): m/e=654.
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.[OH-].[Na+].Cl[CH:13](C)[CH2:14][NH2:15].Cl>O.CO>[NH2:15][CH2:14][CH2:13][CH2:2][S:1][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=1[NH2:3]
Reactant: c1ccc2scnc2c1
Reactant: CC(Cl)CN
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: NCCCSc1ccccc1N
Temperature: 70 °C
Reaction time: 3 h

Procedure:
270 parts of benzothiazole and 160 parts of sodium hydroxide are boiled under reflux for 3 hours in 400 parts of water. After cooling to 70° C., 250 parts of methanol are added, followed by the dropwise addition over a period of 2 hours at 70° C. of a solution of 260 parts of 2-chloropropylamine·HCl in 500 parts of water. After stirring for another 3 hours at 100° C., the mixture is cooled and a solution of 100 parts of sodium hydroxide in 200 parts of water is added to it. The organic phase is separated off, the aqueous phase is washed twice with 200 parts of toluene and the combined organic phases are concentrated by evaporation, leaving 346 parts of 2-(3-aminopropylthio)-aniline in the form of a yellowish liquid boiling at 130° C./0.04 mm.
Reaction SMILES: C([C:4]1[S:8][C:7]2[CH:9]=[CH:10][CH:11]=[C:12]([I:13])[C:6]=2[CH:5]=1)(O)=O>N1C2C(=CC=CC=2)C=CC=1.C(OCC)(=O)C.CCOCC.[Cu]>[I:13][C:12]1[C:6]2[CH:5]=[CH:4][S:8][C:7]=2[CH:9]=[CH:10][CH:11]=1
Reactant: O=C(O)c1cc2c(I)cccc2s1
Agent: [Cu]
Solvent: c1ccc2ncccc2c1
Solvent: CCOCC
Solvent: CCOC(C)=O
Product: Ic1cccc2sccc12
Temperature: 200 °C
Yield: 90.6 %

Procedure:
A mixture of 2-carboxy-4-iodobenzo[b]thiophene (2 g) and copper powder (0.05 g) in quinoline (10 ml) was heated at 200° C. for 2 hours. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (50 ml) and ether (50 ml). The mixture was washed with 5% hydrochloric acid solution (3 times) and brine, dried over magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel eluting with toluene to afford 4-iodobenzo[b]thiophene (1.55 g).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:10](I)=[N:9][N:8]([CH2:12][O:13][C:14](=[O:19])[C:15]([CH3:18])([CH3:17])[CH3:16])[C:5]2=N[CH:7]=1.[CH3:20][O:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1B(O)O.[CH2:31]1COCC1.C(#N)C>C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[Br:1][C:2]1[CH:3]=[C:4]2[C:5](=[CH:31][CH:7]=1)[N:8]([CH2:12][O:13][C:14](=[O:19])[C:15]([CH3:18])([CH3:17])[CH3:16])[N:9]=[C:10]2[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[O:21][CH3:20]
Reactant: C1CCOC1
Reactant: COc1ccccc1B(O)O
Reactant: CC(C)(C)C(=O)OCn1nc(I)c2cc(Br)cnc21
Agent: Cl[Pd]Cl
Agent: [Fe]
Agent: [CH]1[CH][CH][C]([PH+](c2ccccc2)c2ccccc2)[CH]1
Solvent: CC#N
Solvent: ClCCl
Product: COc1ccccc1-c1nn(COC(=O)C(C)(C)C)c2ccc(Br)cc12
Temperature: 60 °C
Reaction time: 4 h
Yield: 63 %

Procedure:
A mixture of 2,2-dimethyl-propionic acid 5-bromo-3-iodo-pyrazolo[3,4-b]pyridin-1-ylmethyl ester (5 g, 11.4 mmol), 2-methoxy-phenyl boronic acid (1.7 g, 11.4 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (420 mg, 0.6 mmol) in THF/Acetonitrile/saturated NaHCO3 (10 ml/10 ml/15 ml) was stirred at 60° C. for 4 hours. The mixture was allowed to cool down to room temperature and then extracted with ethyl acetate (3×). The combined organic layers were extracted with brine, dried with Na2SO4, decanted, and concentrated to dryness. Silica gel chromatography of the crude using a gradient of ethyl acetate and hexane afforded 2,2-dimethyl-propionic acid 5-bromo-3-(2-methoxy-phenyl)-indazol-1-ylmethyl ester (3 g, 63% yield). 1H NMR (500 MHz, DMSO-d6) δ 1.08 (s, 9H), 3.85 (s, 3H), 6.45 (s, 2H), 7.10 (m, 1H), 7.23 (d, 1H), 7.50 (m, 1H), 7.59 (d, 1H), 8.42 (s, 1H), 8.73 (s, 1H).
Reaction SMILES: [N+:1](=[CH2:3])=[N-:2].[C:4]1([CH2:10][C:11](Cl)=[O:12])[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1>CCOCC>[N+:1](=[CH:3][C:11](=[O:12])[CH2:10][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)=[N-:2]
Reactant: O=C(Cl)Cc1ccccc1
Reactant: C=[N+]=[N-]
Solvent: CCOCC
Product: [N-]=[N+]=CC(=O)Cc1ccccc1
Yield: 95.2 %

Procedure:
To diazomethane (40 mmol) in ether (100 ml) at 0° C. was added phenylacetyl chloride (2.65 ml, 20 mmol). After 30 min at 0° C. the excess diazomethane and the ether were blown off with nitrogen, and then under vacuum to leave 1-diazo-3-phenyl-2-propanone as a yellow oil (3.05 g, 95%); δH (CDCl3) 7.2(5H, S, aryl), 5.1(1H, S, CH=N2), 3.5(2H, S, CH2).
Reaction SMILES: [C:1]([O:5][C:6](=[O:38])[NH:7][C:8]([C:10]1[CH:15]=[CH:14][C:13]([CH2:16][NH:17][C:18]([C@H:20]2[N:24]3[C:25](=[O:37])[C:26]([NH:29][CH2:30][C:31]4C=CC=C[CH:32]=4)=[CH:27][N:28]=[C:23]3[CH2:22][CH2:21]2)=[O:19])=[CH:12][CH:11]=1)=[NH:9])([CH3:4])([CH3:3])[CH3:2].[C:39](OC(=O)NC(C1C=CC(CNC([C@H]2N3C(=O)C(N)=CN=C3CC2)=O)=CC=1)=N)(C)(C)[CH3:40].CCC(=O)CC.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>>[C:1]([O:5][C:6](=[O:38])[NH:7][C:8]([C:10]1[CH:15]=[CH:14][C:13]([CH2:16][NH:17][C:18]([C@H:20]2[N:24]3[C:25](=[O:37])[C:26]([NH:29][CH:30]([CH2:31][CH3:32])[CH2:39][CH3:40])=[CH:27][N:28]=[C:23]3[CH2:22][CH2:21]2)=[O:19])=[CH:12][CH:11]=1)=[NH:9])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)NC(=N)c1ccc(CNC(=O)[C@@H]2CCc3ncc(N)c(=O)n32)cc1
Reactant: CC(C)(C)OC(=O)NC(=N)c1ccc(CNC(=O)[C@@H]2CCc3ncc(NCc4ccccc4)c(=O)n32)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CCC(=O)CC
Product: CCC(CC)Nc1cnc2n(c1=O)[C@H](C(=O)NCc1ccc(C(=N)NC(=O)OC(C)(C)C)cc1)CC2
Yield: 24 %

Procedure:
Following a procedure similar to that for the preparation of intermediate 1k, intermediate 1j (100 mg, 0.234 mmol), 3-pentanone (33.8 mg, 0.469 mmol) and NaBH(OAc)3 (139.1 mg, 0.657 mmol) yielded 27.8 mg (24%) of intermediate 11a. MS (ESI) 497.1 (M+H+).
Reaction SMILES: [OH-].[K+].[CH3:3][O:4][C:5]1[C:14]([C:15](=[O:17])[CH3:16])=[C:13]2[C:8]([C:9](=[O:25])[C:10]([CH3:24])=[C:11]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[O:12]2)=[CH:7][CH:6]=1.[C:26]([C:28]1[CH:35]=[CH:34][C:31]([CH:32]=O)=[CH:30][CH:29]=1)#[N:27]>C(O)C.O>[CH3:24][C:10]1[C:9](=[O:25])[C:8]2[C:13](=[C:14]([C:15](=[O:17])[CH:16]=[CH:32][C:31]3[CH:34]=[CH:35][C:28]([C:26]#[N:27])=[CH:29][CH:30]=3)[C:5]([O:4][CH3:3])=[CH:6][CH:7]=2)[O:12][C:11]=1[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: N#Cc1ccc(C=O)cc1
Reactant: COc1ccc2c(=O)c(C)c(-c3ccccc3)oc2c1C(C)=O
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: COc1ccc2c(=O)c(C)c(-c3ccccc3)oc2c1C(=O)C=Cc1ccc(C#N)cc1
Temperature: 25 °C
Yield: 66.4 %

Procedure:
A solution of KOH 50% (3 ml) is added to an equimolar solution of 7-methoxy -8-acetyl-3methylflavone (2.31 g, 0.0075 mol) and 4-cyanobenzaldehyde (0.98 g, 0.0075 mol) in ethanol 95%; the addition is performed under energetic stirring at room temperature. The reaction is left under stirring for one night and then diluted with water and acidified; the precipitate is separated by filtration and dried under vacuum. The compound is crystallized by ethanol to give 2.1 g of product m.p. 223-224C, 1H-NMR (CDCl3)δ:2.18 (s, 3H), 3.96 (s, 3H), 7.04-8.36 (m, 13H).
Reaction SMILES: C(OC(C)C)(=O)C.[C:8]([O:12][C:13]([N:15]1[C@H:19]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[CH:23][CH:22]=2)[CH2:18][C:17](=[CH2:33])[C:16]1=[O:34])=[O:14])([CH3:11])([CH3:10])[CH3:9].[H][H]>[Rh]>[C:8]([O:12][C:13]([N:15]1[C@H:19]([CH2:20][C:21]2[CH:22]=[CH:23][C:24]([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)=[CH:25][CH:26]=2)[CH2:18][C@@H:17]([CH3:33])[C:16]1=[O:34])=[O:14])([CH3:11])([CH3:9])[CH3:10].[C:8]([O:12][C:13]([N:15]1[C@H:19]([CH2:20][C:21]2[CH:22]=[CH:23][C:24]([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)=[CH:25][CH:26]=2)[CH2:18][C@H:17]([CH3:33])[C:16]1=[O:34])=[O:14])([CH3:11])([CH3:9])[CH3:10]
Reactant: [H][H]
Reactant: C=C1C[C@@H](Cc2ccc(-c3ccccc3)cc2)N(C(=O)OC(C)(C)C)C1=O
Agent: [Rh]
Solvent: CC(=O)OC(C)C
Product: C[C@@H]1C[C@@H](Cc2ccc(-c3ccccc3)cc2)N(C(=O)OC(C)(C)C)C1=O
Product: C[C@H]1C[C@@H](Cc2ccc(-c3ccccc3)cc2)N(C(=O)OC(C)(C)C)C1=O
Temperature: 25 °C
Reaction time: 50 h

Procedure:
Isopropyl acetate (1 ml) is added to a mixture of 100 mg (R)-5-biphenyl-4-ylmethyl-3-methylene-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (4-a, R1=Boc) and 10% rhodium on carbon (10 mg). Hydrogen gas (ambient pressure) is applied to the mixture. The mixture is stirred at ambient temperature and pressure for 50 h. The mixture is then filtered over Celites and washed with isopropyl acetate (2×0.5 ml). The mixture is then concentrated in vacuo to give (3R,5S)-5-biphenyl-4-ylmethyl-3-methyl-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (3-a, R1=Boc) and (3S,5S)-5-biphenyl-4-ylmethyl-3-methyl-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (3-b, R1=Boc). Diastereomer ratio 21:79 (3-a, R1=Boc: 3-b, R1=Boc) as determined by hplc. Spectroscopic data in described in WO/2008/083967, for example, Examples 14 and 18.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([C:8]([OH:10])=O)[CH:5]=[CH:4][N:3]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.Cl.[CH3:35][C:36]1[C:44]2[C:43]([N:45]3[CH2:50][CH2:49][CH:48]([NH2:51])[CH2:47][CH2:46]3)=[N:42][CH:41]=[N:40][C:39]=2[NH:38][CH:37]=1>C(Cl)Cl>[CH3:1][C:2]1[CH:7]=[C:6]([C:8]([NH:51][CH:48]2[CH2:47][CH2:46][N:45]([C:43]3[C:44]4[C:36]([CH3:35])=[CH:37][NH:38][C:39]=4[N:40]=[CH:41][N:42]=3)[CH2:50][CH2:49]2)=[O:10])[CH:5]=[CH:4][N:3]=1
Reactant: Cc1c[nH]c2ncnc(N3CCC(N)CC3)c12
Reactant: Cc1cc(C(=O)O)ccn1
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: Cc1cc(C(=O)NC2CCN(c3ncnc4[nH]cc(C)c34)CC2)ccn1
Reaction time: 0.17 h

Procedure:
To a mixture of 2-methyl-4-pyridinecarboxylic acid (41 mg, 0.299 mmol), EDC (86 mg, 0.448 mmol), HOBt (68.6 mg, 0.448 mmol) and DIPEA (0.130 mL, 0.747 mmol) in DCM (1 mL), prestirred for 10 minutes, was added 1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-piperidinamine hydrochloride D11 (80 mg) and the mixture stirred at room temperature for 18 hours. The solvent was removed in vacuo and the mixture purified by MDAP to give the title compound E25 (37 mg), 1H NMR (d6-DMSO) δ 11.52 (1H, s), 8.59 (1H, d), 8.57 (1H, d), 8.22 (1H, s), 7.65 (1H, d), 7.56 (1H, d), 7.07 (1H, s), 4.11-3.99 (3H, m), 3.06 (2H, t), 2.53 (3H, s), 2.37 (3H, s), 1.94 (2H, d), 1.73 (2H, ddd), MS(ES+) 351 [M+H]+.
Reaction SMILES: C(N(CC)CC)C.[N:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[CH:10][C:9]=1[C:18]([OH:20])=O.C1(P([N:35]=[N+:36]=[N-:37])(C2C=CC=CC=2)=O)C=CC=CC=1>O1CCCC1>[N:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[CH:10][C:9]=1[C:18]([N:35]=[N+:36]=[N-:37])=[O:20]
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Reactant: O=C(O)c1ccc2ccccc2n1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: [N-]=[N+]=NC(=O)c1ccc2ccccc2n1
Temperature: -10 °C
Reaction time: 0.17 h
Yield: 263.9 %

Procedure:
47 ml (0.34 mol) of triethylamine are added to a stirred suspension, cooled to -10° C., of 30.0 g (0.17 mol) of quinoline-2-carboxylic acid in 385 ml of anhydrous tetrahydrofuran, and the mixture is stirred at -10° C. for 10 minutes, whereupon a clear solution forms. 73.0 ml (0.34 mol) of diphenylphosphoryl azide are then added dropwise and the reaction mixture is left to stand in a refrigerator at 0° C. for 20 hours. Thereafter, the mixture is stirred into 350 ml of ice-cold dilute NaHCO3 solution. The precipitate formed is separated off by filtration, washed with water and dried in air. 88.9 g (86%) of the title compound are obtained as a pale solid.
Reaction SMILES: [CH2:1]([O:8][C@@H:9]1[C@@H:14]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@H:13]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@@H:12]([CH2:31][O:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH2:11][C:10]1([C:41]1[CH:46]=[CH:45][CH:44]=[C:43]([CH2:47][C:48]2[CH:53]=[CH:52][C:51]([O:54][CH3:55])=[CH:50][CH:49]=2)[CH:42]=1)[OH:40])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:63](Cl)(=[O:65])[CH3:64].C(=O)([O-])O.[Na+]>CN(C)C1C=CN=CC=1.ClCCl.C(OC(=O)C)(=O)C>[CH2:1]([O:8][C@@H:9]1[C@@H:14]([O:15][CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[C@H:13]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@@H:12]([CH2:31][O:32][CH2:33][C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH2:11][C:10]1([O:40][C:63](=[O:65])[CH3:64])[C:41]1[CH:46]=[CH:45][CH:44]=[C:43]([CH2:47][C:48]2[CH:49]=[CH:50][C:51]([O:54][CH3:55])=[CH:52][CH:53]=2)[CH:42]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COc1ccc(Cc2cccc(C3(O)C[C@H](COCc4ccccc4)[C@@H](OCc4ccccc4)[C@H](OCc4ccccc4)[C@H]3OCc3ccccc3)c2)cc1
Reactant: CC(=O)Cl
Agent: CN(C)c1ccncc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)OC(C)=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1ccc(Cc2cccc(C3(OC(C)=O)C[C@H](COCc4ccccc4)[C@@H](OCc4ccccc4)[C@H](OCc4ccccc4)[C@H]3OCc3ccccc3)c2)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of [2R,3S,4R,5R]-2,3,4-trisbenzyloxy-5-benzyloxymethyl-1-[3-(4-methoxybenzyl)phenyl]cyclohexanol (20 mg), triethylamine (0.008 mL) and 4-dimethylamino-pyridine (0.7 mg) in dichloromethane (0.10 mL), acetic anhydride (0.003 mL) was added under cooling with ice and the reaction mixture was stirred at room temperature for two hours. Then, acetyl chloride (0.003 mL) was added thereto under cooling with ice and the reaction mixture was stirred at room temperature for 30 minutes. a saturated sodium hydrogen-carbonate aqueous solution was added thereto and the mixture was extracted with dichloromethane, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was concentrated and the obtained residue was purified by preparative TLC [developing solution=ethyl acetate:n-hexane (2:5)] to obtain the title compound (4.2 mg).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.[CH:9]([C:11]1[CH:12]=[C:13](B(O)O)[CH:14]=[CH:15][C:16]=1[F:17])=[O:10]>>[Cl:1][C:2]1[N:7]=[C:6]([C:13]2[CH:14]=[CH:15][C:16]([F:17])=[C:11]([CH:12]=2)[CH:9]=[O:10])[CH:5]=[CH:4][N:3]=1
Reactant: Clc1ccnc(Cl)n1
Reactant: O=Cc1cc(B(O)O)ccc1F
Product: O=Cc1cc(-c2ccnc(Cl)n2)ccc1F

Procedure:
2,4 dichloropyrimidine and 3-formyl 4-fluorophenyl boronic acid were coupled following procedure A. LC-MS showed the product was >95% pure and had the expected M+H+ of 237.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[CH:13][CH:14]=[C:15]3[C:19]=2[C:18](=O)[CH:17]([CH2:21][CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)[CH2:16]3)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+].CO.S(=O)(=O)(O)O>C1(C)C=CC=CC=1.O>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[CH:13][CH:14]=[C:15]3[C:19]=2[CH2:18][C:17]([CH2:21][CH:22]2[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]2)=[CH:16]3)=[CH:7][CH:6]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)c1ccc(-c2cccc3c2C(=O)C(CC2CCCCC2)C3)cc1
Agent: O=S(=O)(O)O
Agent: [BH4-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CO
Solvent: O
Product: CC(C)(C)c1ccc(-c2cccc3c2CC(CC2CCCCC2)=C3)cc1
Temperature: 50 °C
Reaction time: 3 h
Yield: 85.3 %

Procedure:
82.3 g (229 mmole) 7-(4′-tert-Butyl-phenyl)-2-cyclohexylmethyl-indan-1-one were dissolved in 292 ml toluene in a 1 l-roundbottom flask equipped with a reflux condenser. 9.5 g (1.1 eq.) sodium borohydride were added. Then 40 ml (4.3 eq.) methanol were added at 50° C. and the mixture was stirred for 3 h at 50° C. An additional 1 g of sodium borohydride and 5 ml methanol were added and the mixture was stirred another 2 h at 50° C. 2M sulphuric acid was added until the gas evolution ceased. After addition of 100 ml water the layers were separated and the organic layer was washed two times with 2M sulphuric acid and once with a saturated sodium chloride solution. The solvent was evaporated and the crude indanol was dissolved in approx. 350 ml of toluene. After addition of 0.7 g p-toluene sulfonic acid the mixture was heated to reflux using a Dean-Stark-trap until TLC showed complete conversion (90 min). The solution was washed twice with a saturated NaHCO3-solution, once with water and once with a saturated sodium chloride solution. Drying over magnesium sulphate, evaporation of the solvent and crystallization from 800 ml ethanol afforded 67.3 g (86%) of the desired indene as white crystals. 1H-NMR (400 MHz, CDCl3): δ=7.45, 7.33, 7.25, 7.14 (4×m, 7H, aromatic), 6.69 (s, 1H, ═CH), 3.35 (s, 2H, benzylic), 2.34 (d, 2H, aliphatic), 1.71-1.50 (m, 6H, aliphatic), 1.39 (s, 9H, C(CH3)3), 1.24-0.87 (m, 5H, aliphatic) ppm.
Reaction SMILES: [CH3:1][C:2]1([CH3:7])[NH:6][CH2:5][CH2:4][S:3]1.[C:8]([OH:15])(=[O:14])[CH2:9][CH2:10][C:11]([NH2:13])=[O:12]>CC1(C)NCCS1>[C:8]1(=[O:15])[O:14][C:11](=[O:12])[CH2:10][CH2:9]1.[CH3:1][C:2]1([CH3:7])[NH:6][CH2:5][CH2:4][S:3]1.[CH3:1][C:2]1([CH3:7])[NH:6][CH2:5][CH2:4][S:3]1.[C:8]([OH:15])(=[O:14])/[CH:9]=[CH:10]\[C:11]([NH2:13])=[O:12]
Reactant: NC(=O)CCC(=O)O
Agent: CC1(C)NCCS1
Product: NC(=O)/C=C\C(=O)O
Product: O=C1CCC(=O)O1

Procedure:
Examples of sulfidoamidocarboxylic acids represented by the formula I may include DMT-amic acids originating in dimethylthiazolidine such as DMT-succinamic acid (amic acid formed by the reaction of succinic anhydride with DMT (dimethyl thiazolidine)), DMT-maleamic acid (amic acid formed by the reaction of maleic anhydride with DMT), DMT-phthalamic acid (amic acid formed by the reaction of phthalic anhydride with DMT), DMT-trimellitamic acid (amic acid formed by the reaction of trimellitic anhydride with DMT), DMT-pyromellitamic acid (amic acid formed by the reaction of pyromellitic dianhydride with DMT), DMT-mellitamic acid (amid acid formed by the reaction of mellitic trianhydride with DMT), DMT-hexahydrophthalamic acid (amic acid formed by the reaction of hexahydrophthalic anhydride with DMT), DMT-citraconamic acid (amic acid formed by the reaction of citrononic anhydride with DMT), DMT-itaconamic acid (amic acid formed by the reaction of itaconic anhydride with DMT), DMT-naphthalenedicarboxylamic acid (amic acid formed by the reaction of naphthalenedicarboxylic anhydride with DMT), amic acid formed by the reaction of maleated methyl cyclohexene tetracarboxylic dianhydride with DMT, DMT-endomethylenetetrahydrophthalamic acid (amic acid formed by the reaction of endomethylenetetrahydrophthalic anhydride with DMT), DMT-chlorendoamic acid (amic acid formed by the reaction of chlorendic anhydride with DMT), DMT-methylendomethylenetetrahydrophthalamic acid (amic acid formed by the reaction of methylendomethylenetetrahydrophthalic anhydride with DMT), DMT-methyltetrahydrophthalamic acid (amic acid formed by the reaction of methyltetrahydrophthalic anhydride with DMT), amic acid formed by the reaction of methylnorbornene-2,3-dicarboxylic anhydride with DMT, DMT-tetrahydrophthalamic acid (amic acid formed by the reaction of tetrahydrophthalic anhydride with DMT), amic acid formed by the reaction of cyclopentanetetracarboxylic anhydride with DMT, amic acid formed by the reaction of glutaric anhydride with DMT, DMT-dodecenylsuccinamic acid (amic acid formed by the reaction of dodecenylsuccinic anhydride with DMT), and DMT-hexahydromethylphthalamic acid (amic acid formed by the reaction of hexahydromethylphthalic anhydride with DMT);