Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]=[N+:2]=[N-:3].[F:4][C:5]1[CH:6]=[C:7]([C:12](O)([CH3:14])[CH3:13])[CH:8]=[C:9]([F:11])[CH:10]=1.C(O)(C(F)(F)F)=O.[OH-].[Na+]>C(Cl)(Cl)Cl>[N:1]([C:12]([C:7]1[CH:8]=[C:9]([F:11])[CH:10]=[C:5]([F:4])[CH:6]=1)([CH3:14])[CH3:13])=[N+:2]=[N-:3]
Reactant: [N-]=[N+]=N
Reactant: CC(C)(O)c1cc(F)cc(F)c1
Agent: [Na+]
Agent: [OH-]
Solvent: O=C(O)C(F)(F)F
Solvent: ClC(Cl)Cl
Product: CC(C)(N=[N+]=[N-])c1cc(F)cc(F)c1
Temperature: -5 °C
Reaction time: 20 h

Procedure:
Hydrogen azide (2M in toluene, 1.5 mol) was added to the solution of 2-(3,5-difluoro-phenyl)-propan-2-ol (Preparation 50, 145 g, 0.84 mol, 1 eq) in chloroform (1 L) and the content of the flask was cooled to −5° C. The mixture of TFA (2.5 mol, 2.98 eq) with chloroform (1:1) was added dropwise at such a rate to keep the internal temperature below −5° C. After the addition was complete, the reaction mixture was allowed to warm to room temperature and stirring was continued for 20 h. The reaction was poured into 2M sodium hydroxide and layers were separated. The aqueous phase was extracted two times with chloroform and combined organic extracts were washed with brine and dried over anhydrous magnesium sulfate. After removal of the solvent, the title compound was used in the next step without further purification (171 g, 0.87 mol, 100%).
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[N:11][N:12]([C:15]3[CH:23]=[CH:22][C:18]([C:19]([OH:21])=O)=[CH:17][N:16]=3)[C:13]=2[OH:14])=[C:5]([CH3:24])[CH:4]=1)#[N:2].C1C=C2N=NN(O)C2=CC=1.O.Cl.[CH2:37]([N:39]=[C:40]=NCCCN(C)C)C.C(N(CC)CC)C.Cl.CNC.Cl>CN(C=O)C.CO.O>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[N:11][N:12]([C:15]3[CH:23]=[CH:22][C:18]([C:19]([N:39]([CH3:40])[CH3:37])=[O:21])=[CH:17][N:16]=3)[C:13]=2[OH:14])=[C:5]([CH3:24])[CH:4]=1)#[N:2]
Reactant: Cc1cc(C#N)ccc1-c1cnn(-c2ccc(C(=O)O)cn2)c1O
Reactant: CCN=C=NCCCN(C)C
Agent: CNC
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: CO
Product: Cc1cc(C#N)ccc1-c1cnn(-c2ccc(C(=O)N(C)C)cn2)c1O
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 65.6 %

Procedure:
Combined 6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid (107 mg, 0.334 mmol), HOBT hydrate (77 mg, 0.501 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (96 mg, 0.501 mmol) in DMF (2 mL), and added triethylamine (0.188 mL, 1.336 mmol), stirred at ambient temperature for 5 minutes and dimethylamine hydrochloride (54.5 mg, 0.668 mmol) was added. The reaction was stirred at 50° C. for 3 hours, then cooled to ambient temperature and diluted with MeOH (5 mL), water (5 mL), and acidified to pH 5 using 1N aqueous hydrochloric acid, to give a solid which was filtered, washed with water, and dried under vacuum to give the title compound (76.2 mg, 0.219 mmol, 66%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.43 (s, 3 H) 3.01 (br. s., 6 H) 7.65 (dd, J=8.08, 1.52 Hz, 1 H) 7.70-7.82 (m, 2 H) 8.02-8.20 (m, 2 H) 8.37 (br. s., 1 H) 8.56 (dd, J=2.27, 0.76 Hz, 1 H) 13.11 (br. s., 1 H). ESI-MS m/z [M+H]+ 348.3.
Reaction SMILES: [O:1]=[C:2]1[NH:7][C:6]2[CH:8]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[S:10][C:5]=2[C:4](=[O:17])[N:3]1[CH:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]1.Cl[CH2:32][C:33]1[O:34][C:35]([CH2:38][CH3:39])=[N:36][N:37]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH2:38]([C:35]1[O:34][C:33]([CH2:32][N:7]2[C:6]3[CH:8]=[C:9]([C:11]4[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=4)[S:10][C:5]=3[C:4](=[O:17])[N:3]([CH:18]3[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]3)[C:2]2=[O:1])=[N:37][N:36]=1)[CH3:39]
Reactant: CC(C)(C)OC(=O)N1CCC(n2c(=O)[nH]c3cc(-c4ccccc4)sc3c2=O)CC1
Reactant: CCc1nnc(CCl)o1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCc1nnc(Cn2c(=O)n(C3CCN(C(=O)OC(C)(C)C)CC3)c(=O)c3sc(-c4ccccc4)cc32)o1

Procedure:
According to GP1 tert-butyl 4-(2,4-dioxo-6-phenyl-1,4-dihydrothieno[3,2-d]pyrimidin-3(2H)-yl)piperidine-1-carboxylate (750 mg; compound B50) is reacted with 2-(chloromethyl)-5-ethyl-1,3,4-oxadiazole (257 mg; compound D4) in the presence of potassium carbonate (242 mg) in DMF (10 ml). Using WU1 the title compound is obtained as a solid.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.[C:16]([CH2:20][CH2:21][C:22](Cl)=[O:23])([O:18][CH3:19])=[O:17]>O1CCCC1>[OH:8][C:4]1[CH:3]=[C:2]([NH:1][C:22](=[O:23])[CH2:21][CH2:20][C:16]([O:18][CH3:19])=[O:17])[CH:7]=[CH:6][CH:5]=1
Reactant: Nc1cccc(O)c1
Reactant: COC(=O)CCC(=O)Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: COC(=O)CCC(=O)Nc1cccc(O)c1
Temperature: 25 °C
Yield: 88 %

Procedure:
To an ice cold solution of 3-aminophenol (21.8 g, 0.2 mol) and triethylamine (21.3 g, 0.2 mol) in tetrahydrofuran (250 ml) is added a solution of 3-carbomethoxypropanoyl chloride (30.1 g, 0.2 mol) in tetrahydrofuran. The reaction is allowed to warm to room temperature and is filtered through a pad of Celite and silica gel. The solvent is removed in vacuo to give a solid. Recrystallization from ethyl acetate gives 39.3 g (88% yield) of product, m.p. 144.5°-146° C.
Reaction SMILES: [CH3:1][C:2]([CH3:9])([CH3:8])[C@@H:3]([OH:7])[CH2:4][C:5]#[CH:6].C(N(CC)CC)C.FC(F)(F)S(O[Si:23]([CH2:28][CH3:29])([CH2:26][CH3:27])[CH2:24][CH3:25])(=O)=O.C(=O)(O)[O-].[Na+]>ClCCl>[CH3:1][C:2]([CH3:9])([CH3:8])[C@@H:3]([O:7][Si:23]([CH2:28][CH3:29])([CH2:26][CH3:27])[CH2:24][CH3:25])[CH2:4][C:5]#[CH:6]
Reactant: C#CC[C@H](O)C(C)(C)C
Reactant: CC[Si](CC)(CC)OS(=O)(=O)C(F)(F)F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: C#CC[C@H](O[Si](CC)(CC)CC)C(C)(C)C
Temperature: 0 °C
Reaction time: 0.67 h
Yield: 92.3 %

Procedure:
A mixture of (S)-5,5-dimethyl-1-hexyn-4-ol (1.96 g 16 mmol), triethylamine (4.5 ml, 32 mmol) and dry dichloromethane (30 ml) was cooled to 0° C. under a nitrogen atmosphere. Triethylsilyl trifluoromethanesulphonate (5.4 ml, 24 mmol) was slowly added and the mixture stirred at 0° C. for a further 40 min. The mixture was treated with saturated sodium bicarbonate solution (60 ml) and the organic layer separated. The aqueous layer was extracted with dichloromethane (3×20 ml) and the combined dichloromethane extracts dried (MgSO4) and evaporated. The residue was purified by column chromatorgaphy (silica eluted with Petroleum ether 40-60°) to yield the title compound 3.55 g (95%).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]([CH2:41][C:42](=[O:68])/[CH:43]=[CH:44]/[C:45]2[CH:50]=[CH:49][C:48]([O:51][C:52](=[O:67])[C:53]3[CH:58]=[CH:57][C:56]([O:59][CH2:60][CH2:61][CH2:62][C:63]([F:66])([F:65])[F:64])=[CH:55][CH:54]=3)=[CH:47][CH:46]=2)[C:11]([C:14](=[O:40])/[CH:15]=[CH:16]/[C:17]2[CH:22]=[CH:21][C:20]([O:23][C:24](=[O:39])[C:25]3[CH:30]=[CH:29][C:28]([O:31][CH2:32][CH2:33][CH2:34][C:35]([F:38])([F:37])[F:36])=[CH:27][CH:26]=3)=[CH:19][CH:18]=2)([OH:13])[OH:12])=[CH:6][CH:5]=1)([O-])=O.CCCCCC.C[N:76](C)C=O>O.[Zn]>[NH2:76][C:8]1[CH:9]=[C:4]([NH2:1])[CH:5]=[CH:6][C:7]=1[CH:10]([CH2:41][C:42](=[O:68])/[CH:43]=[CH:44]/[C:45]1[CH:50]=[CH:49][C:48]([O:51][C:52](=[O:67])[C:53]2[CH:58]=[CH:57][C:56]([O:59][CH2:60][CH2:61][CH2:62][C:63]([F:66])([F:65])[F:64])=[CH:55][CH:54]=2)=[CH:47][CH:46]=1)[C:11]([C:14](=[O:40])/[CH:15]=[CH:16]/[C:17]1[CH:22]=[CH:21][C:20]([O:23][C:24](=[O:39])[C:25]2[CH:30]=[CH:29][C:28]([O:31][CH2:32][CH2:33][CH2:34][C:35]([F:38])([F:37])[F:36])=[CH:27][CH:26]=2)=[CH:19][CH:18]=1)([OH:13])[OH:12]
Reactant: CN(C)C=O
Reactant: O=C(/C=C/c1ccc(OC(=O)c2ccc(OCCCC(F)(F)F)cc2)cc1)CC(c1ccc([N+](=O)[O-])cc1)C(O)(O)C(=O)/C=C/c1ccc(OC(=O)c2ccc(OCCCC(F)(F)F)cc2)cc1
Agent: [Zn]
Solvent: CCCCCC
Solvent: O
Product: Nc1ccc(C(CC(=O)/C=C/c2ccc(OC(=O)c3ccc(OCCCC(F)(F)F)cc3)cc2)C(O)(O)C(=O)/C=C/c2ccc(OC(=O)c3ccc(OCCCC(F)(F)F)cc3)cc2)c(N)c1

Procedure:
7.60 g (7.64 mmol) of 2-(4-nitrophenyl)-1,3 di[(2E)-3-{4-[(4-(4,4,4-trifluorobutoxy)benzoyl)oxy]phenyl}prop-2-enoyl]propanediol are dissolved in a mixture of 45 ml of N,N-dimethylformamide and 5 ml water. 12.39 g (45.84 mmol) ferric chloride hexahydrate are added. 4.99 g (76.4 mmol) Zinc powder are added portionwise within 40 min. The mixture is allowed to react for 2 hours. The reaction mixture is then partitioned between ethyl acetate and water and filtered. The organic phase is washed repeatedly with water, dried over sodium sulfate, filtered and concentrated by rotary evaporation. Chromatography of the residue on 1000 g silica gel using toluene:ethyl acetate 1:1 as eluant and crystallization form ethylacetate:hexane mixture to yield 4.30 g of 2-(2,4-Diaminophenyl)-1,3 di[(2E)-3-{4-[(4-(4,4,4-trifluorobutoxy)benzoyl)oxy]phenyl}prop-2-enoyl]propanediol.
Reaction SMILES: [CH:1]12[N:7]([C:8]3[CH:9]=[CH:10][C:11]([N+:20]([O-])=O)=[C:12]([C:14]#[C:15][CH2:16][N:17]([CH3:19])[CH3:18])[CH:13]=3)[CH:4]([CH2:5][CH2:6]1)[CH2:3][CH2:2]2>O.[Fe]>[CH:1]12[N:7]([C:8]3[CH:9]=[CH:10][C:11]([NH2:20])=[C:12]([C:14]#[C:15][CH2:16][N:17]([CH3:19])[CH3:18])[CH:13]=3)[CH:4]([CH2:5][CH2:6]1)[CH2:3][CH2:2]2
Reactant: CN(C)CC#Cc1cc(N2C3CCC2CC3)ccc1[N+](=O)[O-]
Agent: [Fe]
Solvent: O
Product: CN(C)CC#Cc1cc(N2C3CCC2CC3)ccc1N
Yield: 48.2 %

Procedure:
3-[5-(7-Azabicyclo[2.2.1]heptan-7-yl)-2-nitro-phenyl]-N,N-dimethyl-prop-2-yn-1-amine 26 (340 mg, 1.14 mmol), iron (634 mg, 11.36 mmol) and ferrous sulfate heptahydrate (316 mg, 1.136 mmol) were suspended in water (1 mL) and refluxed for 20 min. The reaction was filtered and the solid washed with methanol and dichloromethane. The filtrate was concentrated and purified by silica gel chromatography using (0-5% methanol in dichloromethane) to provide 4-(7-azabicyclo[2.2.1]heptan-7-yl)-2-(3-dimethylaminoprop-1-ynyl)aniline 27 (148 mg, 48% yield). LC/MS m/z 270.3 [M+H]+, retention time 0.25 min (RP-C18, 10-99% CH3CN/0.05% TFA over 3 min).
Reaction SMILES: CCCCCC.C([Li])CCC.[C:12]1([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH:17]=[CH:16][C:15]([C:18]2[N:23]=[C:22]([C:24]3[CH:29]=[CH:28][C:27]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[CH:26][CH:25]=3)[N:21]=[C:20]([C:36]3[CH:41]=[CH:40][C:39](Br)=[CH:38][CH:37]=3)[N:19]=2)=[CH:14][CH:13]=1.Br[C:50]1[N:55]=[C:54]([C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][N:57]=2)[CH:53]=[CH:52][CH:51]=1>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.O1CCCC1>[C:12]1([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH:17]=[CH:16][C:15]([C:18]2[N:23]=[C:22]([C:24]3[CH:29]=[CH:28][C:27]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[CH:26][CH:25]=3)[N:21]=[C:20]([C:36]3[CH:41]=[CH:40][C:39]([C:58]4[N:57]=[C:56]([C:54]5[CH:53]=[CH:52][CH:51]=[CH:50][N:55]=5)[CH:61]=[CH:60][CH:59]=4)=[CH:38][CH:37]=3)[N:19]=2)=[CH:14][CH:13]=1
Reactant: Brc1ccc(-c2nc(-c3ccc(-c4ccccc4)cc3)nc(-c3ccc(-c4ccccc4)cc3)n2)cc1
Reactant: Brc1cccc(-c2ccccn2)n1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: c1ccc(-c2ccc(-c3nc(-c4ccc(-c5ccccc5)cc4)nc(-c4ccc(-c5cccc(-c6ccccn6)n5)cc4)n3)cc2)cc1
Temperature: -78 °C
Reaction time: 0.25 h
Yield: 67.2 %

Procedure:
Under a stream of argon, 2.1 ml of a hexane solution containing 3.3 mmol of butyl lithium was slowly added to 70 ml of tetrahydrofuran cooled to −78° C. in which 1.62 g of 2,4-bis(4-biphenylyl)-6-(4-bromophenyl)-1,3,5-triazine obtained in Reference Example 3 had been dissolved. After stirring at −78° C. for 15 minutes, 0.91 g of dichloro(tetramethylethylenediamine)zinc(II) was added thereto and stirred at −78° C. for 10 minutes and then at room temperature for 2 hours. A 20 ml portion of tetrahydrofuran prepared by dissolving 0.85 g of 6-bromo-2,2′-bipyridyl and 0.14 g of tetrakis(triphenylphosphine)palladium(0) therein was added to this solution and stirred under heating reflux for 4 hours. The reaction solution was concentrated under a reduced pressure and the thus obtained solid was recrystallized from dichloromethane-methanol. The thus obtained crude product was washed with chloroform to obtain a white solid of the intended 6-{4-[4,6-bis(4-biphenylyl)-1,3,5-triazin-2-yl]phenyl}-2,2′-bipyridyl (1.24 g, yield 67%).
Reaction SMILES: [Cl:1][C:2]([Cl:28])([Cl:27])[CH2:3][O:4][C:5](=[O:26])[NH:6][C:7]1[CH:12]=[CH:11][C:10]([S:13][C:14]2[CH:19]=[CH:18][C:17]([C:20](Cl)=[O:21])=[CH:16][C:15]=2[N+:23]([O-:25])=[O:24])=[CH:9][CH:8]=1.[S:29]1[CH:33]=[N:32][N:31]=[C:30]1[NH2:34]>C1(C)C=CC=CC=1>[Cl:1][C:2]([Cl:28])([Cl:27])[CH2:3][O:4][C:5](=[O:26])[NH:6][C:7]1[CH:12]=[CH:11][C:10]([S:13][C:14]2[CH:19]=[CH:18][C:17]([C:20](=[O:21])[NH:34][C:30]3[S:29][CH:33]=[N:32][N:31]=3)=[CH:16][C:15]=2[N+:23]([O-:25])=[O:24])=[CH:9][CH:8]=1
Reactant: Nc1nncs1
Reactant: O=C(Nc1ccc(Sc2ccc(C(=O)Cl)cc2[N+](=O)[O-])cc1)OCC(Cl)(Cl)Cl
Solvent: Cc1ccccc1
Product: O=C(Nc1ccc(Sc2ccc(C(=O)Nc3nncs3)cc2[N+](=O)[O-])cc1)OCC(Cl)(Cl)Cl
Yield: 100 %

Procedure:
The product of Example 162b (300 mg, 0.6197 mmol) and [1,3,4]Thiadiazol-2-ylamine (62 mg, 0.6197 mmol) in toluene (10 mL) were reacted as in Example 162c to yield the title compound (340 mg, 100% yield).
Reaction SMILES: [CH2:1]([N:8]1[CH2:12][CH2:11][CH2:10][C:9]1=[CH:13][C:14]1C=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH3:23])[CH:15]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C(O)C.[Pt].[H][H]>[CH2:1]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[CH:14]=[CH:15][C:16]([O:22][CH3:23])=[C:17]([O:20][CH3:21])[CH:18]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COc1ccc(C=C2CCCN2Cc2ccccc2)cc1OC
Reactant: [H][H]
Agent: [Pt]
Solvent: CCO
Product: COc1ccc(C2CCCN2Cc2ccccc2)cc1OC

Procedure:
Dissolve 3 g of 1-benzyl-2-(3,4-dimethoxybenzylidene)pyrrolidine in ethanol and hydrogenate with platinum/hydrogen. Distil the hydrogenated product under a vacuum to obtain 2.3 g (77% of theory) of title compound (b.p. 173° at 0.007 mm of Hg).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([C:13]3[CH:18]=[CH:17][C:16]([S:19]([CH3:22])(=[O:21])=[O:20])=[CH:15][CH:14]=3)=[CH:11][CH:10]=[C:9]2[CH3:23])=[CH:4][CH:3]=1.C=O.[OH-].[Na+].CCCCCC.[C:34]([O:37][CH2:38]C)(=[O:36])[CH3:35]>CC(O)=O>[C:34]([O:37][CH2:38][C:10]1[CH:11]=[C:12]([C:13]2[CH:18]=[CH:17][C:16]([S:19]([CH3:22])(=[O:21])=[O:20])=[CH:15][CH:14]=2)[N:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[C:9]=1[CH3:23])(=[O:36])[CH3:35]
Reactant: Cc1ccc(-c2ccc(S(C)(=O)=O)cc2)n1-c1ccc(F)cc1
Reactant: CCOC(C)=O
Agent: C=O
Agent: [Na+]
Agent: [OH-]
Solvent: CCCCCC
Solvent: CC(=O)O
Product: CC(=O)OCc1cc(-c2ccc(S(C)(=O)=O)cc2)n(-c2ccc(F)cc2)c1C
Temperature: 52.5 °C
Yield: 22 %

Procedure:
To a solution of 1-(4-fluorophenyl)-2-methyl-5-[4-(methylsulfonyl)phenyl]-1H-pyrrole (Example 1) (500 mg, 2.87 mmol) in AcOH (5 ml), formaldehyde (0.22 ml, 40% solution in water, 2.87 mmol) was added. After heating at 50-55° C. for 90 minutes, the reaction mixture was cooled and poured over ice. The solution was made alkaline with 2N NaOH and extracted with methylene chloride. The organic fractions were washed with water and with brine, dried (MgSO4), filtered and concentrated to give the crude product (780 mg) as a yellowish liquid. Chromatography (silica gel, hexane/ethyl acetate, 6/4) gave [1-(4-fluorophenyl)-2-methyl-5-[4-(methylsulfonyl)phenyl]-1H-pyrrol-3-yl]methyl acetate (250 mg, 22%) as a white solid: mp (DSC) 151° C. Anal Calc'd. for C21H20NSFO4 : C, 62.83; H, 5.02; N, 3.49. Found: C, 62.48; H, 5.16; N, 3.37.
Reaction SMILES: [C:1]1([C:7]2([C:10]#[N:11])[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:12][S:13](O)(=[O:15])=[O:14]>C(Cl)(Cl)Cl>[C:10]([C:7]1([C:1]2[CH:6]=[CH:5][C:4]([S:13]([Cl:12])(=[O:15])=[O:14])=[CH:3][CH:2]=2)[CH2:8][CH2:9]1)#[N:11]
Reactant: N#CC1(c2ccccc2)CC1
Reactant: O=S(=O)(O)Cl
Solvent: ClC(Cl)Cl
Product: N#CC1(c2ccc(S(=O)(=O)Cl)cc2)CC1
Temperature: 25 °C

Procedure:
To a solution of 1-phenylcyclopropanecarbonitrile (0.5 g, 3.5 mmol) in 5 mL of chloroform was added 0.5 mL of ClSO3H at 0° C. After stirring at rt stirred overnight, the reaction mixture was poured into ice-water (50 mL) and the product was extracted with CHCl3 (75 mL). The extracts were washed with water (50 mL) and brine (50 mL), dried over anhydrous MgSO4, and concentrated to give the title compound. 1H NMR (500 MHz, CD3OD): δ 8.08 (2H, d), 7.77 (2H, d), 1.60 (2H, t), 1.21 (2H, t).
Reaction SMILES: [CH3:1][C:2]([CH3:14])([CH3:13])[CH:3]=[N:4][C@H:5]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH3:6].CC(C)(C)C(=O)[C:18]([OH:20])=[O:19]>C(OCC)C>[CH3:14][C:2]([CH3:13])([CH3:1])[C:3](=[N:4][C@H:5]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH3:6])[C:18]([OH:20])=[O:19]
Reactant: C[C@H](N=CC(C)(C)C)c1ccccc1
Reactant: CC(C)(C)C(=O)C(=O)O
Solvent: CCOCC
Product: C[C@H](N=C(C(=O)O)C(C)(C)C)c1ccccc1
Temperature: 0 °C
Reaction time: 6 h
Yield: 81.2 %

Procedure:
8.9 g (47 mmol) of (S)-(2,2-dimethylpropylidene)-(1-phenylethyl)-amine (J. L. Fauchure, C. Petermann, Helv. Chim. Acta 1980, 63, 824) were dissolved in 10 ml of diethyl ether with the exclusion of moisture. 8.1 g (50 mmol) of trimethylpyruvic acid in 10 ml of diethyl ether were added dropwise to this solution while cooling with ice. Subsequently, the mixture was stirred at 0° C. for a further 2 hours and at room temperature for 6 hours. Colorless crystals form over 2 days and these were suspended in 50 ml of diethyl ether, filtered off and washed twice with 5 ml of diethyl ether each time. After drying in a vacuum there were obtained 8.9 g (81%) of (S)-3,3-dimethyl-2-(1-phenylethylimino)-butyric acid (internal salt) of melting point 135°-136° C. [α]=-14.4 (c=0.16, CH2Cl2).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:17]=[CH:16][C:6]([CH2:7][O:8][C:9]2[C:14](=[O:15])[CH:13]=[CH:12][NH:11][CH:10]=2)=[CH:5][CH:4]=1.[Br:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21](Br)[N:20]=1>CS(C)=O>[Br:18][C:19]1[N:20]=[C:21]([N:11]2[CH:12]=[CH:13][C:14](=[O:15])[C:9]([O:8][CH2:7][C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:17][CH:16]=3)=[CH:10]2)[CH:22]=[CH:23][CH:24]=1
Reactant: Brc1cccc(Br)n1
Reactant: COc1ccc(COc2c[nH]ccc2=O)cc1
Solvent: CS(C)=O
Product: COc1ccc(COc2cn(-c3cccc(Br)n3)ccc2=O)cc1

Procedure:
A mixture of 3-[(4-methoxybenzyl)oxyJpyridin-4(1H)-one (2.31 g, 10 mmol), 2,6-dibromopyridine (4.74 g, 20 mmol), and K2C03 (3.45 g, 25 mmol) in DMSO was heated at 120° C. overnight. After cooling to it, the solid was removed by filtration and the DMSO solution was purified by flash chromatography to give 6′-bromo-3-[(4-methoxybenzyl)oxy]-4H-1,2′-bipyridin-4-one. ′H NMR (600 MHz, DMSO): δ 8.42 (dd, J−7.7, 2.4 Hz, 1H); 8.22 (d, J=2.4 Hz, 1H); 8.03-7.96 (m, 1H); 7.96-7.89 (m, 1H); 7.71 (t, J−7.7 Hz, 1H); 7.40 (d, J=8.4 Hz, 2H); 6.96 (d, J=8.4 Hz, 2H); 6.42 (d, J=7.7 Hz, 1H); 5.03 (s, 2H); 3.76 (s, 3H). 264.1; MS (M+H)+387.
Reaction SMILES: Cl[C:2]1[N:3]=[C:4]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[C:5]2[S:10][C:9]([CH2:11][N:12]([CH3:20])[S:13]([CH2:16][CH2:17][CH2:18][Cl:19])(=[O:15])=[O:14])=[CH:8][C:6]=2[N:7]=1.CC1(C)C(C)(C)OB([C:35]2[CH:43]=[CH:42][CH:41]=[C:40]3[C:36]=2[CH:37]=[N:38][NH:39]3)O1>>[NH:39]1[C:40]2[C:36](=[C:35]([C:2]3[N:3]=[C:4]([N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[C:5]4[S:10][C:9]([CH2:11][N:12]([CH3:20])[S:13]([CH2:16][CH2:17][CH2:18][Cl:19])(=[O:15])=[O:14])=[CH:8][C:6]=4[N:7]=3)[CH:43]=[CH:42][CH:41]=2)[CH:37]=[N:38]1
Reactant: CN(Cc1cc2nc(Cl)nc(N3CCOCC3)c2s1)S(=O)(=O)CCCCl
Reactant: CC1(C)OB(c2cccc3[nH]ncc23)OC1(C)C
Product: CN(Cc1cc2nc(-c3cccc4[nH]ncc34)nc(N3CCOCC3)c2s1)S(=O)(=O)CCCCl

Procedure:
3-Chloro-propane-1-sulfonic acid (2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-methylamide was reacted with 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-indazole in general procedure A. Purification on silica yielded 3-chloro-propane-1-sulfonic acid [2-(1H-indazol-4-yl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl]-methyl-amide.
Reaction SMILES: [C:1]([C:3]1[C:4]([C:17]([F:20])([F:19])[F:18])=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:12][C:13](=[NH:16])[NH:14][OH:15])[CH:7]=[CH:6]2)#[N:2].[Br:21][C:22]1[CH:23]=[C:24]([CH:28]=[CH:29][CH:30]=1)[C:25](O)=O>>[Br:21][C:22]1[CH:23]=[C:24]([C:25]2[O:15][N:14]=[C:13]([CH2:12][N:8]3[C:9]4[C:5](=[C:4]([C:17]([F:19])([F:20])[F:18])[C:3]([C:1]#[N:2])=[CH:11][CH:10]=4)[CH:6]=[CH:7]3)[N:16]=2)[CH:28]=[CH:29][CH:30]=1
Reactant: N#Cc1ccc2c(ccn2CC(=N)NO)c1C(F)(F)F
Reactant: O=C(O)c1cccc(Br)c1
Product: N#Cc1ccc2c(ccn2Cc2noc(-c3cccc(Br)c3)n2)c1C(F)(F)F

Procedure:
Synthesized as described in Example 72 from 2-[5-cyano-4-(trifluoromethyl)-1H-indol-1-yl]-N-hydroxyethanimidamide and 3-bromobenzoic acid: MS (ESI): m/z 449 (M+1).
Reaction SMILES: [C:1]([O:5][C:6]([C@@H:8]1[CH2:12][CH2:11][C:10](=[O:13])[N:9]1[C:14](=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[CH2:21]Br)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:24]([O:26][P:27]([O:31]CC)[O:28][CH2:29][CH3:30])[CH3:25]>>[C:1]([O:5][C:6]([C@@H:8]1[CH2:12][CH2:11][C:10](=[O:13])[N:9]1[C:14](=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[CH2:21][P:27]([O:28][CH2:29][CH3:30])([O:26][CH2:24][CH3:25])=[O:31])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CCOP(OCC)OCC
Reactant: CC(C)(C)OC(=O)[C@@H]1CCC(=O)N1C(=O)c1ccccc1CBr
Product: CCOP(=O)(Cc1ccccc1C(=O)N1C(=O)CC[C@H]1C(=O)OC(C)(C)C)OCC
Temperature: 70 °C
Yield: 82.7 %

Procedure:
A mixture of (S)-1-(2-bromomethyl-benzoyl)-5-oxo-pyrrolidine-2-carboxylic acid tert-butyl ester (898 mg, 2.4 mmol) and triethylphosphite (432 mg, 2.4 mmol) was heated at 70° C. for 4 h. After cooling, the residue was purified by flash chromatography (ethyl acetate) to afford the title compound as a clear viscous oil (872 mg, 84%): 1H NMR (400 MHz, CDCl3) δ 1.17 (3H, t, J=7.0 Hz), 1.26 (3H, t, J=7.0 Hz), 1.53 (9H, s), 2.07-2.14 (1H, m), 2.43-2.69 (3H, m), 3.12 (1H, dd, J 22.4, 15.0 Hz), 3.62 (1H, dd, J 22.1, 15.0 Hz), 3.84-4.06 (4H, m), 4.87 (1H, dd, J 8.9, 4.8 Hz), 7.31-7.46 (4H, m).
Reaction SMILES: O[CH2:2][CH:3]([CH2:5][OH:6])O.[CH:7]([CH:9]=[CH2:10])=[O:8]>>[C:5]([OH:6])(=[O:8])[CH:3]=[CH2:2].[CH:7]([CH:9]=[CH2:10])=[O:8]
Reactant: OCC(O)CO
Agent: C=CC=O
Product: C=CC(=O)O

Procedure:
In the process for producing acrylic acid from glycerin via acrolein, it is preferred that: glycerin is introduced into a first reactor to conduct the dehydration reaction in the dehydration step; the acrolein-containing gas discharged from the first reactor is introduced into a condenser to be cooled at a pressure Pc lower than atmospheric pressure in the partial-condensation step; the purified gas discharged from the condenser is introduced into a second reactor to conduct the oxidation reaction of acrolein in the acrolein oxidation step; and the purified gas obtained by the partial-condensation step is introduced into the second reactor while acrolein contained in the purified gas remains in a gaseous state, wherein an inlet pressure of the second reactor is adjusted at a pressure Ps higher than the pressure Pc. When acrylic acid is produced from glycerin via acrolein in this manner, it becomes possible to efficiently produce acrylic acid while suppressing loss of acrolein due to polymerization of acrolein. For raising the pressure of the acrolein-containing gas, a pressure riser may be employed. Specifically, it is preferred that the pressure of the acrolein-containing gas is adjusted at the pressure Ps by introducing the purified gas discharged from the condenser into a pressure riser, followed by introducing an adjustment gas into the pressure riser or compressing in the pressure riser.