Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C@@H:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C@H:17]([O:24][C:25]3[CH:26]=[CH:27][C:28]4[N:29]([C:31]([N:34]5[CH2:39][CH2:38][CH2:37][CH2:36][C@@H:35]5[CH3:40])=[N:32][N:33]=4)[CH:30]=3)[CH2:16][CH2:15]2)=[O:12])[N:7]([C:41]2[CH:42]=[N:43][N:44]([CH2:46][CH2:47][OH:48])[CH:45]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.[CH3:58][S:59](Cl)(=[O:61])=[O:60]>C(Cl)Cl>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C@@H:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C@H:17]([O:24][C:25]3[CH:26]=[CH:27][C:28]4[N:29]([C:31]([N:34]5[CH2:39][CH2:38][CH2:37][CH2:36][C@@H:35]5[CH3:40])=[N:32][N:33]=4)[CH:30]=3)[CH2:16][CH2:15]2)=[O:12])[N:7]([C:41]2[CH:42]=[N:43][N:44]([CH2:46][CH2:47][O:48][S:59]([CH3:58])(=[O:61])=[O:60])[CH:45]=2)[N:6]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: C[C@H]1CCCCN1c1nnc2ccc(O[C@@H]3CC[C@H](NC(=O)Nc4cc(C(C)(C)C)nn4-c4cnn(CCO)c4)c4ccccc43)cn12
Reactant: CS(=O)(=O)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: C[C@H]1CCCCN1c1nnc2ccc(O[C@@H]3CC[C@H](NC(=O)Nc4cc(C(C)(C)C)nn4-c4cnn(CCOS(C)(=O)=O)c4)c4ccccc43)cn12
Reaction time: 2 h

Procedure:
To an ice-bath cooled solution of Intermediate 187b (250 mg, 0.38 mmol) in DCM (4 mL) was added DIPEA (267 μL, 1.53 mmol) followed by methanesulfonyl chloride (60 μL, 0.77 mmol). The reaction mixture was stirred for 2 h and then quenched with water. The aqueous phase was extracted with DCM (×3) and the combined organic layers were washed with brine, dried (MgSO4) and concentrated in vacuo to afford the title compound (Quantitative). Product used in the following step without further purification. LCMS (Method 4): Rt 3.25 min, m/z 732 [MH+].
Reaction SMILES: [CH3:1][C:2]1[S:6][C:5]([C:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[S:9][N:8]=2)=[N:4][N:3]=1.S(=O)(=O)(O)O.[N+:21]([O-])([OH:23])=[O:22]>C(Cl)Cl>[CH3:1][C:2]1[S:6][C:5]([C:7]2[C:11]3[CH:12]=[C:13]([N+:21]([O-:23])=[O:22])[CH:14]=[CH:15][C:10]=3[S:9][N:8]=2)=[N:4][N:3]=1
Reactant: Cc1nnc(-c2nsc3ccccc23)s1
Reactant: O=[N+]([O-])O
Agent: O=S(=O)(O)O
Solvent: ClCCl
Product: Cc1nnc(-c2nsc3ccc([N+](=O)[O-])cc23)s1
Temperature: 0 °C

Procedure:
To a mixture of 3-(5-methyl-1,3,4-thiadiazol-2-yl)-1,2-benzisothiazole(6.8 g, 0.0291 mol) and conc. sulfuric acid at 10° C. is added 90% nitric acid (3.20 ml, 0.582 mol) dropwise. The resultant mixture is stirred 90 min at 0-10° C. and poured into ice water with stirring. Filtration affords a solid which is stirred in hot methylene chloride and filtered to afford the title compound as a tan solid (mp 239-240° C.) which is identified by NMR analysis.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:24]([O:25][CH3:26])=[CH:23][C:6]2[S:7][C:8]([C:10]([NH:12][C:13]3[CH:22]=[CH:21][CH:20]=[CH:19][C:14]=3[C:15]([O:17]C)=[O:16])=[O:11])=[CH:9][C:5]=2[CH:4]=1.[OH-].[Na+]>CO.C1COCC1>[CH3:1][O:2][C:3]1[C:24]([O:25][CH3:26])=[CH:23][C:6]2[S:7][C:8]([C:10]([NH:12][C:13]3[CH:22]=[CH:21][CH:20]=[CH:19][C:14]=3[C:15]([OH:17])=[O:16])=[O:11])=[CH:9][C:5]=2[CH:4]=1
Reactant: COC(=O)c1ccccc1NC(=O)c1cc2cc(OC)c(OC)cc2s1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: COc1cc2cc(C(=O)Nc3ccccc3C(=O)O)sc2cc1OC
Temperature: 25 °C
Reaction time: 2 h
Yield: 87.9 %

Procedure:
To a stirred solution of methyl 2-(5,6-dimethoxybenzo[b]thiophene-2-carboxamido)benzoate (650 mg, 1.75 mmol) in MeOH (9 mL) and THF (20 mL) was added 2N NaOH (9 mL) dropwise at room temperature. The resulting solution was stirred at room temperature for 2 hours. The reaction was quenched with 1N HCl and diluted with water. The resulting suspension was filtered and the solid was dried under vacuum to afford 2-(5,6-dimethoxybenzo[b]thiophene-2-carboxamido)benzoic acid (550 mg, 88%). LC-MS (ES-API); rt 9.22 min; m/z calculated for C18H15NO5S [M+Na]+ 380.1, found 380.0.
Reaction SMILES: [F:1][C:2]1[CH:33]=[CH:32][C:5]([CH2:6][CH2:7][C:8]2[CH:16]=[CH:15][C:14]([CH:17]([O:23][CH2:24][CH2:25][C:26]3[N:30]([CH3:31])[CH:29]=[N:28][CH:27]=3)[C:18]3[S:19][CH:20]=[CH:21][N:22]=3)=[CH:13][C:9]=2[C:10](O)=[O:11])=[CH:4][CH:3]=1.Cl.[C:35]([O:39][C:40](=[O:47])[C@H:41]([CH2:43][CH2:44][S:45][CH3:46])[NH2:42])([CH3:38])([CH3:37])[CH3:36].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.Cl>CN(C1C=CN=CC=1)C.CN(C=O)C.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][CH2:7][C:8]2[CH:16]=[CH:15][C:14]([CH:17]([O:23][CH2:24][CH2:25][C:26]3[N:30]([CH3:31])[CH:29]=[N:28][CH:27]=3)[C:18]3[S:19][CH:20]=[CH:21][N:22]=3)=[CH:13][C:9]=2[C:10]([NH:42][C@@H:41]([CH2:43][CH2:44][S:45][CH3:46])[C:40]([O:39][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:47])=[O:11])=[CH:32][CH:33]=1
Reactant: CSCC[C@H](N)C(=O)OC(C)(C)C
Reactant: Cn1cncc1CCOC(c1ccc(CCc2ccc(F)cc2)c(C(=O)O)c1)c1nccs1
Agent: CN(C)c1ccncc1
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: ClCCCl
Product: CSCC[C@H](NC(=O)c1cc(C(OCCc2cncn2C)c2nccs2)ccc1CCc1ccc(F)cc1)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A mixture of 2-(4-fluorophenethyl)-5-[1-(thiazol-2-yl)-2-(1-methylimidazol-5-yl)ethoxymethyl]benzoic acid (0.47 g, 1.06 mmol) (from Example 63), DMAP (0.62 g, 5.05 mmol), L-methionine tert-butyl ester HCl (0.62 g, 3.02 mmol), EDC (0.39 g, 2.02 mmol) and HOBT (0.137 g, 1.01 mmol) in DMF (25 ml) was stirred at ambient temperature under a nitrogen atmosphere for 16 hours. The reaction was evaporated to dryness and washed with aqueous citric acid (1M, 10 ml) and extracted with dichloromethane (20 ml). The extracts were washed with saturated brine, dried and filtered. Purification by flash column chromatography eluting with dichloromethanel methanol (95:5, 9:1 and 85:15) gave a gum. This was dissolved in ethyl acetate and treated with 1M ethereal HCl (10 ml). The resulting solid precipitate was isolated by centrifuging, further washing with diethyl ether and drying under high vacuum to give tert-butyl (2S)-2- (2-(4-fluorophenethyl)-5-[1-(thiazol-2-yl)-2-(1 -methylimidazol-5-yl)ethoxymethyl]benzoylamino}-4-methylsulfanylbutyrate as a white solid, (0.366 g, 55%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:14]=[CH:15][C:16]=1[O:17][CH3:18])[O:6][CH2:7][C:8](=[O:13])[CH2:9][N+:10]([O-])=O.[ClH:19].[H][H]>[Pd].CO>[ClH:19].[NH2:10][CH2:9][C:8](=[O:13])[CH2:7][O:6][C:5]1[CH:14]=[CH:15][C:16]([O:17][CH3:18])=[C:3]([O:2][CH3:1])[CH:4]=1
Reactant: COc1ccc(OCC(=O)C[N+](=O)[O-])cc1OC
Reactant: [H][H]
Agent: [Pd]
Agent: Cl
Solvent: CO
Product: COc1ccc(OCC(=O)CN)cc1OC

Procedure:
To a MeOH (7 ml) solution of the compound (0.660 g) obtained in Example 19-(2), 10% Pd—C (0.330 g) and an aqueous solution of 1N HCl (14 ml) were added and the mixture was stirred at room temperature for 5 hours in a hydrogen gas atmosphere. The insoluble matter was filtered off and the filtrate was concentrated to give the titled compound (0.715 g, brown amorphous.)
Reaction SMILES: [C:1](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[C:15]1([C@H:21]([N:23]2[CH2:28][CH2:27][O:26][C@@H:25]([C:29]3[CH:34]=[CH:33][C:32]([NH:35][C@@H:36]4[CH2:40][CH2:39][O:38][CH2:37]4)=[CH:31][CH:30]=3)[CH2:24]2)[CH3:22])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C=O>ClC(Cl)C>[CH3:1][N:35]([C:32]1[CH:33]=[CH:34][C:29]([C@@H:25]2[O:26][CH2:27][CH2:28][N:23]([C@@H:21]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH3:22])[CH2:24]2)=[CH:30][CH:31]=1)[C@@H:36]1[CH2:40][CH2:39][O:38][CH2:37]1
Reactant: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Reactant: C[C@H](c1ccccc1)N1CCO[C@@H](c2ccc(N[C@@H]3CCOC3)cc2)C1
Agent: C=O
Agent: [Na+]
Solvent: CC(Cl)Cl
Product: C[C@H](c1ccccc1)N1CCO[C@@H](c2ccc(N(C)[C@@H]3CCOC3)cc2)C1
Reaction time: 2 h
Yield: 99.8 %

Procedure:
Sodium triacetoxyborohydride (2.4 g, 11.3 mmol) was added to a solution of 4-((1R)-1-phenylethyl)-(2S)-2-(4-(N-((3R)-tetrahydrofuran-3yl)amino)phenyl)-morpholine (1.3 g, 3.69 mmol) and formalin (35%, 1.6 g, 18.6 mmol) in dichloroethane (50 mL) at room temperature. After stirring for 2 hours, the resulting suspension was partitioned between ethyl acetate and 1 N sodium hydroxide. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with brine, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel chromatography eluting 5-10% methanol in chloroform to furnish (2S)-2-(4-(N-methyl-N-((3R)-tetrahydrofuran-3-yl)amino)phenyl)-4-((1R)-1-phenylethyl)morpholine (1.35 g, 100%) as a pale yellow oil.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][S:5]([O-:8])(=[O:7])=[O:6].[Na+].[NH:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH:11]1[C:16]([OH:18])=[O:17]>[OH-].[Na+]>[C:16]([CH:11]1[CH2:12][N:13]([CH2:2][CH2:3][CH2:4][S:5]([OH:8])(=[O:7])=[O:6])[CH2:14][CH2:15][NH:10]1)([OH:18])=[O:17]
Reactant: O=C(O)C1CNCCN1
Reactant: O=S(=O)([O-])CCCBr
Agent: [Na+]
Agent: [OH-]
Product: O=C(O)C1CN(CCCS(=O)(=O)O)CCN1

Procedure:
Sodium 3-bromo-propane-1-sulphonate (2.25 g, 0.01 mole) was added to a solution of piperazine-2-carboxylic acid (1.3 g, 0.01 mole) in aqueous sodium hydroxide (0.9 g NaOH/30 ml H2O). The resulting solution was maintained at 60°-65° for 12 h. The product, 3((±)-2-carboxypiperazin-4-yl)-propane-1-sulphonic acid, was isolated by passage of the reaction mixture through Dowex-AG-1-acetate resin. Evaporation of the column filtrate and aqueous washings and recrystallization of the crude product from a 50% aqueous ethanol solution yielded 3-((±)-2-carboxy-piperazin-4-yl)-propane-1-sulphonic acid (500 mg) as a white crystalline solid, m.p. 190°-191°.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:16]([NH:18][CH2:19][C:20]2[C:21](=[O:28])[NH:22][C:23]([CH3:27])=[CH:24][C:25]=2[CH3:26])=[O:17])[C:5]2[CH:6]=[N:7][N:8]([CH:11]3[CH2:15][CH2:14][CH2:13][CH2:12]3)[C:9]=2[CH:10]=1.[I-].[Na+].C1CCN2C(=NCCC2)CC1.[CH3:42][C:43]([OH:47])([C:45]#[CH:46])[CH3:44]>[Zn].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.C1COCC1.CCOC(C)=O.O.CS(C)=O>[CH:11]1([N:8]2[C:9]3[CH:10]=[C:2]([C:46]#[C:45][C:43]([OH:47])([CH3:44])[CH3:42])[CH:3]=[C:4]([C:16]([NH:18][CH2:19][C:20]4[C:21](=[O:28])[NH:22][C:23]([CH3:27])=[CH:24][C:25]=4[CH3:26])=[O:17])[C:5]=3[CH:6]=[N:7]2)[CH2:15][CH2:14][CH2:13][CH2:12]1
Reactant: C#CC(C)(C)O
Reactant: Cc1cc(C)c(CNC(=O)c2cc(Br)cc3c2cnn3C2CCCC2)c(=O)[nH]1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [I-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: C1CCOC1
Solvent: C1CCC2=NCCCN2CC1
Product: Cc1cc(C)c(CNC(=O)c2cc(C#CC(C)(C)O)cc3c2cnn3C2CCCC2)c(=O)[nH]1
Temperature: 85 °C
Reaction time: 0.17 h

Procedure:
To a 10 mL microwave vial containing a mixture of 6-bromo-1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide (0.12 g, 0.271 mmol), sodium iodide (8.11 mg, 0.054 mmol) and zinc (3.54 mg, 0.054 mmol) were added DMSO (2.5 mL), TEA (0.075 mL, 0.541 mmol), and DBU (0.082 mL, 0.541 mmol). The suspension was stirred and degassed with N2 for 5 min. Next added in 2-methyl-3-butyn-2-ol (0.131 mL, 1.353 mmol) and Pd(Ph3P)4 (0.031 g, 0.027 mmol). The reaction vial was sealed and stirred with heating at 85° C. (heat block) for 3 h. The mixture was then diluted into water and 20% THF/EtOAc. The contents were stirred and the layers were separated. The organic layer was washed with brine, dried over MgSO4, filtered through Celite, and concentrated in vacuo. The residue was dried on hi-vacuum pump overnight. The crude product was purified by silica gel chromatography (eluent: 5-80% gradient chloroform (containing 10% 2M ammonia in methanol) in DCM). The collected product was purified by reverse phase HPLC (Gradient B: 15-75%; A: Water+0.1% TFA. B: CH3CN+0.1% TFA). The product was suspended in 10% MeOH/CHCl3. Next added 0.5 g Silicycle carbonate resin and stirred for 15 min. After standing for 10 min, the contents were filtered through celite and concentrated in vacuo. The product was further concentrated from DCM and MTBE and then dried in hi-vac oven at 45° C. overnight. The title compound was collected as a white solid (38 mg, 30%); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.47-1.52 (m, 6H), 1.64-1.73 (m, 2H), 1.80-1.91 (m, 2H), 1.92-2.02 (m, 2H), 2.06-2.15 (m, 5H), 2.18-2.23 (m, 3H), 4.28-4.38 (m, 2H), 5.25 (quin, J=7.07 Hz, 1H), 5.52 (s, 1H), 5.84-5.91 (m, 1H), 7.54 (d, J=1.01 Hz, 1H), 7.93 (s, 1H), 8.35 (s, 1H), 8.60 (t, J=4.93 Hz, 1H), 11.51 (br. s., 1H); LC-MS (ES) m/z=446.9 [M+H]
Reaction SMILES: [CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3]1.[C:11](Cl)(=[O:15])[C:12]([Cl:14])=[O:13]>C(OCC)C>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([C:11](=[O:15])[C:12]([Cl:14])=[O:13])=[CH:3]1
Reactant: Cn1ccc2ccccc21
Reactant: O=C(Cl)C(=O)Cl
Solvent: CCOCC
Product: Cn1cc(C(=O)C(=O)Cl)c2ccccc21
Yield: 72.2 %

Procedure:
To a 100 ml volume three-necked flask, N-methylindole (5.0 g) and diethylether (35 ml) were added under a nitrogen atmosphere, and added oxalyl chloride (9.7 g) at less than 5° C. The mixture was stirred under ice-cooling for 3 hours, and the precipitated solids were collected by suction filtration, washed with cold diethylether, and dried under reduced pressure to give 6.1 g of 2-(1-methyl-1H-indol-3-yl)-2-oxoacetyl chloride (26-a).
Reaction SMILES: [CH:1]([O:8][CH2:9][CH3:10])([O:5]CC)OCC.[F:11][CH:12]([F:21])[C:13](=[O:20])[CH2:14][C:15]([O:17][CH2:18][CH3:19])=O>>[CH2:9]([O:8][C:1](=[O:5])/[C:14](=[CH:15]\[O:17][CH2:18][CH3:19])/[C:13](=[O:20])[CH:12]([F:21])[F:11])[CH3:10]
Reactant: CCOC(OCC)OCC
Reactant: CCOC(=O)CC(=O)C(F)F
Product: CCO/C=C(\C(=O)OCC)C(=O)C(F)F
Temperature: 95 °C
Reaction time: 0.5 h

Procedure:
Process step c): 778.1 g (5.25 mol) of triethyl orthoformate were charged in a stirred vessel, the pressure within the vessel was slowly reduced to 170 mbar and the triethyl orthoformate was heated to 92° C. 134.3 g (0.35 mol-100% conversion in process steps a) and b) assumed) of ethyl 4,4-difluoroacetoacetate (in the form of a suspension coming from process step b)) were added at 92° C. to 95° C. within 4 hours. Thereafter, the reaction mixture was stirred at 95° C. for further 30 minutes. During the entire reaction time low boiling compounds were continuously removed by distillation under reduced pressure. Afterwards, the triethyl orthoformate was distilled by lowering the pressure accordingly. The resulting concentrated product suspension was cooled down to room temperature and 70.2 g of xylenes were added. The resulting suspension (178 g) comprised 40.0% (w/w) of the desired product (GC analysis, quantification with internal standard). This corresponds to an overall yield over the two synthetic steps of 91.6%, based on ethyl difluoroacetate used.
Reaction SMILES: [F:1][C:2]([F:11])([F:10])[C:3]1[CH:4]=[C:5]([CH2:8][OH:9])[S:6][CH:7]=1.[H-].[Na+].Br[C:15]1[CH:20]=[CH:19][N:18]([C:21]2[CH:22]=[CH:23][C:24]3[N:28]=[C:27]([CH:29]4[CH2:31][CH2:30]4)[N:26]([CH3:32])[C:25]=3[CH:33]=2)[C:17](=[O:34])[CH:16]=1.O>CC(N(C)C)=O>[CH:29]1([C:27]2[N:26]([CH3:32])[C:25]3[CH:33]=[C:21]([N:18]4[CH:19]=[CH:20][C:15]([O:9][CH2:8][C:5]5[S:6][CH:7]=[C:3]([C:2]([F:10])([F:1])[F:11])[CH:4]=5)=[CH:16][C:17]4=[O:34])[CH:22]=[CH:23][C:24]=3[N:28]=2)[CH2:30][CH2:31]1
Reactant: Cn1c(C2CC2)nc2ccc(-n3ccc(Br)cc3=O)cc21
Reactant: OCc1cc(C(F)(F)F)cs1
Agent: [H-]
Agent: [Na+]
Solvent: CC(=O)N(C)C
Solvent: O
Product: Cn1c(C2CC2)nc2ccc(-n3ccc(OCc4cc(C(F)(F)F)cs4)cc3=O)cc21
Temperature: 120 °C
Reaction time: 0.5 h
Yield: 15 %

Procedure:
To a solution of (4-(trifluoromethyl)thiophen-2-yl)methanol (50 mg) in DMA (2 ml) was added NaH (60% in oil, 18.3 mg) at room temperature, and the mixture was stirred for 30 min. 4-Bromo-1-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one (79 mg) was added to the mixture, and the mixture was heated at 120° C. for 30 min under microwave irradiation. The mixture was poured into water and extracted with EtOAc. The organic layer was separated, washed with saturated NaHCO3 solution and brine successively, dried over MgSO4 and concentrated in vacuo. The residue was purified by column chromatography (EtOAc/MeOH), followed by crystallized from hot EtOAc to give the title compound (15.3 mg) as pale yellow crystals.
Reaction SMILES: C(O)(=O)[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1.C(O)(=O)C1C=CC=C(C(O)=O)C=1.C[NH:26][CH2:27][CH2:28][CH2:29][CH2:30]CCN(C)C.C(O)(=O)CCCCC(O)=O.C(O)(=O)CCCCCCCC(O)=O.NC1CCC(C(C2CCC(N)CC2)(C)C)CC1>>[CH2:10]([CH2:2][CH2:3][CH2:4][CH2:5][C:6]([OH:8])=[O:7])[CH2:9][CH2:30][CH2:29][CH2:28][CH2:27][NH2:26]
Reactant: O=C(O)c1ccc(C(=O)O)cc1
Reactant: CNCCCCCCN(C)C
Agent: CC(C)(C1CCC(N)CC1)C1CCC(N)CC1
Agent: O=C(O)CCCCC(=O)O
Agent: O=C(O)CCCCCCCC(=O)O
Product: NCCCCCCCCCCC(=O)O

Procedure:
as well as polyamides resulting from terephthalic acid and/or isophthalic acid and trimethyl hexamethylene diamine, polyamides resulting from adipic acid and meta xylylenediamines, polyamides resulting from adipic acid, azelaic acid and 2,2-bis(p-aminocyclohexyl)propane and polyamides resulting from terephthalic acid and 4,4'-diamino-dicyclohexylmethane.
Reaction SMILES: [CH:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[O:15][N:14]=[C:13]([C:16]3[CH:21]=[CH:20][C:19]([CH2:22][OH:23])=[CH:18][CH:17]=3)[N:12]=2)=[CH:7][CH:6]=1)([CH3:3])[CH3:2].C(C1C=CC(C2N=C(C3C=CC(C=O)=NC=3)ON=2)=CC=1)C(C)C>>[CH:1]([O:4][C:5]1[CH:6]=[CH:7][C:8]([C:11]2[O:15][N:14]=[C:13]([C:16]3[CH:21]=[CH:20][C:19]([CH:22]=[O:23])=[CH:18][CH:17]=3)[N:12]=2)=[CH:9][CH:10]=1)([CH3:3])[CH3:2]
Reactant: CC(C)Oc1ccc(-c2nc(-c3ccc(CO)cc3)no2)cc1
Agent: CC(C)Cc1ccc(-c2noc(-c3ccc(C=O)nc3)n2)cc1
Product: CC(C)Oc1ccc(-c2nc(-c3ccc(C=O)cc3)no2)cc1

Procedure:
The title compound was prepared from 4-[5-(4-isopropoxy-phenyl)-[1,2,4]oxadiazol-3-yl]-phenylmethanol by procedures analogous to those described in Preparation 4F for the preparation of 5-[3-(4-isobutyl-phenyl)-[1,2,4]oxadiazol-5-yl]-pyridine-2-carbaldehyde.
Reaction SMILES: Br[C:2]1[CH:8]=[C:7]([F:9])[C:5]([NH2:6])=[C:4]([Cl:10])[CH:3]=1.[CH2:11]([O:13][C:14]1[C:15]([F:23])=[C:16](B(O)O)[CH:17]=[CH:18][CH:19]=1)[CH3:12]>>[Cl:10][C:4]1[CH:3]=[C:2]([C:16]2[CH:17]=[CH:18][CH:19]=[C:14]([O:13][CH2:11][CH3:12])[C:15]=2[F:23])[CH:8]=[C:7]([F:9])[C:5]=1[NH2:6]
Reactant: Nc1c(F)cc(Br)cc1Cl
Reactant: CCOc1cccc(B(O)O)c1F
Product: CCOc1cccc(-c2cc(F)c(N)c(Cl)c2)c1F
Yield: 43.2 %

Procedure:
The title compound (65 mg) was prepared from 4-bromo-2-chloro-6-fluoroaniline (120 mg, 0.53 mmol) and 3-ethoxy-2-fluorophenylboronic acid (120 mg, 0.69 mmol) as a colourless liquid.
Reaction SMILES: [Cl:1][C:2]1[C:3]2[CH:10]=[CH:9][N:8]([S:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)(=[O:13])=[O:12])[C:4]=2[N:5]=[CH:6][N:7]=1.[Li+].CC([N-]C(C)C)C.[I:28]I.O>C1COCC1.C(Cl)Cl>[Cl:1][C:2]1[C:3]2[CH:10]=[C:9]([I:28])[N:8]([S:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)(=[O:13])=[O:12])[C:4]=2[N:5]=[CH:6][N:7]=1
Reactant: II
Reactant: O=S(=O)(c1ccccc1)n1ccc2c(Cl)ncnc21
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: ClCCl
Solvent: O
Solvent: C1CCOC1
Product: O=S(=O)(c1ccccc1)n1c(I)cc2c(Cl)ncnc21
Reaction time: 3 h

Procedure:
To a stirred solution of 4-chloro-7-(phenylsulfonyl)-7H-pyrrolo[2,3-d]-pyrimidine (5.0 g, 0.017 mol) in THF (200 mL) under inert atmosphere, at −78° C., was added 2.0 M LDA solution (9.8 mL, 0.0195 mol) over a period of 15 min. After 1 h a solution of iodine (4.97 g, 0.0196 mol) in THF (50 mL) was added dropwise over a period of 15 min. The resulting solution was stirred for a further 3 h. Water (10 mL) was then added and the mixture allowed to reach r.t. The mixture was diluted with DCM (1 l), washed with brine (2×100 mL), dried and concentrated under reduced pressure. The resulting solid was triturated with MeCN to afford the 4-chloro-6-iodo-7-(phenylsulfonyl)-7H-pyrrolo[2,3-d]pyrimidine. 1H NMR (CDCl3, 400 MHz) 7.05 (1H, s), 7.50 (2H, t), 7.60 (1H, t), 8.20 (2H, d) and 8.65 (1H, br s).
Reaction SMILES: [C:1]([OH:7])(=[O:6])[CH2:2][CH2:3][CH2:4][CH3:5].[CH:8]#[C:9][CH2:10][NH:11][C@H:12]1[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[CH2:14][CH2:13]1>C(OC(C)C)(C)C>[CH:8]#[C:9][CH2:10][NH:11][C@H:12]1[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[CH2:14][CH2:13]1.[C:1]([O-:7])(=[O:6])[CH2:2][CH2:3][CH2:4][CH3:5]
Reactant: CCCCC(=O)O
Agent: C#CCN[C@@H]1CCc2ccccc21
Solvent: CC(C)OC(C)C
Product: CCCCC(=O)[O-]
Reaction time: 1.5 h

Procedure:
To a solution of 60 mg (0.58 mmol, 1.0 eq) pentanoic acid in 0.5 ml diisopropyl ether a solution of 100 mg (0.58 mmol) rasagiline in 0.5 ml diisopropyl ether was added. After stirring for 90 min the solvent was removed in vacuo. The residue was dried in high vacuum for 5 h to yield a thick oil (158 mg, 0.58 mmol, quant.).
Reaction SMILES: C[O:2][C:3](=[O:20])[CH:4]=[CH:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]([CH3:15])([CH3:14])[CH3:13])=[CH:8][C:7]=1[NH:16][CH:17]([CH3:19])[CH3:18].[OH-].[Na+].Cl>CO.O>[C:12]([C:9]1[CH:10]=[CH:11][C:6]([CH:5]=[CH:4][C:3]([OH:20])=[O:2])=[C:7]([NH:16][CH:17]([CH3:19])[CH3:18])[CH:8]=1)([CH3:15])([CH3:13])[CH3:14]
Reactant: COC(=O)C=Cc1ccc(C(C)(C)C)cc1NC(C)C
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: CC(C)Nc1cc(C(C)(C)C)ccc1C=CC(=O)O
Temperature: 25 °C
Reaction time: 12 h
Yield: 99.9 %

Procedure:
3-(4-tert-butyl-2-isopropylaminophenyl)acrylic acid methyl ester (0.14 mmol, 37.7 mg) and NaOH (0.68 mmol, 27.39 mg) were added in methanol and water. The reaction mixture was stirred for 12 hrs at room temperature. The reaction mixture was acidified with 5% HCl solution. The mixture was concentrated in vacuo to yield a yellow solid (36.56 mg, 100%).
Reaction SMILES: [NH2:1][C:2]1[C:7]([NH2:8])=[CH:6][CH:5]=[CH:4][N:3]=1.[OH-].[K+].[C:11](=S)=[S:12].Cl>C(Cl)Cl.O.C(O)C>[SH:12][C:11]1[NH:8][C:7]2[CH:6]=[CH:5][CH:4]=[N:3][C:2]=2[N:1]=1
Reactant: S=C=S
Reactant: Nc1cccnc1N
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: ClCCl
Solvent: CCO
Product: Sc1nc2ncccc2[nH]1
Reaction time: 1 h
Yield: 112.9 %

Procedure:
A solution of 2,3-diaminopyridine (10.0 g, 92 mmol), potassium hydroxide (6.8 g, 123 mmol)k, CS2 (9.4 g, 123 mmol), ethanol (100 mL), and water (20 mL) was stirred at reflux for 5 hours, then at ambient temperature overnight. Evaporation in vacuo gave a residue which was dissolved in CH2Cl2, acidified to pH 5 with 2N hydrochloric acid, and stirred for 1 hour. The resultant suspension was filtered to give 15.7 g of 2-mercaptoimidazopyridine as a brown solid. A solution of the 2-mercaptoimidazopyridine (4.23 g, 28 mmol) and geranyl chloride (4.8 g, 28 mmol) in methanol (40 mL) and 2N NaOH/H2O (40 mmol) was stirred in 16 hours at ambient temperature, evaporated, dissolved in CH2Cl2, washed with water, and dried over Na2SO4. Flash chromatography (Merck Kieselgel, 5% MeOH/CH2Cl2) gave 2.0 g (25%) of 2-[(3,7-dimethyl-2,6(E)-octadienyl)thio]-1H-imidazo[4,5-6]pyridine, 1.0 g of which was converted to its oxalate salt. m.p. 118°-121° C. NMR (DMSO-d6)δ8.20(d, J=5 Hz, 1H), 7.60(m, 2H), 5.40(d, J=7 Hz, 1H), 5.10(d, J=6 Hz, 1H), 4.00(d, J=6 Hz, 2H), 2.00(m, 4H), 1.70(s, 3H), 1.61(s, 3H), 1.60(s, 3H).
Reaction SMILES: [C:1]([O:5][C:6](=[O:33])[CH:7]=[C:8](OS(C(F)(F)F)(=O)=O)[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]C1C=CC2CCCNC=2N=1)([CH3:4])([CH3:3])[CH3:2].S1C(B(O)O)=CC2C=CC=CC1=2.C(=O)([O-])[O-].[K+].[K+].C(=O)([O-])O.[Na+]>C1(C)C=CC=CC=1>[C:1]([O:5][C:6](=[O:33])[CH:7]=[CH:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)C=C(CCCCCCc1ccc2c(n1)NCCC2)OS(=O)(=O)C(F)(F)F
Agent: O=C([O-])O
Agent: O=C([O-])[O-]
Agent: OB(O)c1cc2ccccc2s1
Solvent: Cc1ccccc1
Product: CCCCCCC=CC(=O)OC(C)(C)C
Temperature: 95 °C

Procedure:
To a stirred solution of 9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-3-(trifluoromethanesulfonyloxy)-non-2-enoic acid tert-butyl ester 29-6 (100 mg, 0.20 mmol) in toluene (2.5 mL) was added palladium(tetrakis)-triphenylphosphine (23 mg, 0.020 mmol), benzo[b]thiophene-2-boronic acid (50 mg, 0.41 mmol) and potassium carbonate (56 mg, 0.41 mmol). The resulting suspension was heated at 90-100° C. for 2 hours, and then was allowed to cool to ambient temperature. The reaction mixture was then poured into saturated aqueous sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried with anhydrous magnesium sulfate, filtered, and concentrated at reduced pressure. The resulting oil was purified by flash column chromatography over silica gel with 4:1 ethyl acetate/hexanes to give 29-7b as a colorless oil.