Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [I:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.C1(C)C=C(C)C=C(C)C=1S(O[NH2:20])(=O)=O.[C:22]1([C:28]#[C:29][C:30]([O:32][CH3:33])=[O:31])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(=O)([O-])[O-].[K+].[K+]>ClCCl.CN(C)C=O.C(OCC)C>[I:1][C:2]1[CH:7]=[CH:6][C:5]2[N:4]([N:20]=[C:28]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:29]=2[C:30]([O:32][CH3:33])=[O:31])[CH:3]=1
Reactant: Cc1cc(C)c(S(=O)(=O)ON)c(C)c1
Reactant: COC(=O)C#Cc1ccccc1
Reactant: Ic1cccnc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: CN(C)C=O
Solvent: CCOCC
Product: COC(=O)c1c(-c2ccccc2)nn2cc(I)ccc12
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 11.7 %

Procedure:
Dichloromethane (10 mL) and 3-Iodopyridine (928 mg, 4.53 mmol) were charged to a 100 mL round-bottomed flask equipped with a magnetic stir bar. This colorless solution was cooled on an ice bath and O-(mesitylsulfonyl)hydroxylamine (975 mg, 4.53 mmol) in dichloromethane (10 mL) was added dropwise over 5 minutes. After to stirring at room temperature for 30 minutes, the solvent was removed by rotory evaporation to give a white solid. Methyl phenylpropiolate (1000 mg, 6.24 mmol) was added in dimethylformamide (9 mL). Potassium carbonate (2504 mg, 18.12 mmol) was added. Reaction slowly turned dark green. After stirring at room temp for 2 hours, the reaction was poured into diethyl ether (300 mL and extracted 8×25 mL water. The solvent was removed from the organic portion by rotory evaporation. The crude product was dissolved in a minimum amount of dichloromethane and charged to a 90 g “Single Sep” silica gel cartridge and eluted with 0 to 40% ethyl acetate in hexanes over 1000 mL. The title compound (200 mg, 12%) was isolated as an orange solid. 1H NMR (500 MHz, CHLOROFORM-D) δ ppm 3.83 (s, 3H) 7.46 (m, 3H) 7.59 (dd, J=9.16, 1.53 Hz, 1H) 7.75 (m, 2H) 8.00 (dd, J=9.31, 0.76 Hz, 1H) 8.82 (s, 1H). LCMS: 2.4 minutes, M+1=379.
Reaction SMILES: O1CC[CH2:4]OO1.[F:7][C:8]([F:17])([F:16])[O:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[ClH:18]>[Cl-].[Zn+2].[Cl-]>[F:7][C:8]([F:16])([F:17])[O:9][C:10]1[CH:15]=[CH:14][C:13]([CH2:4][Cl:18])=[CH:12][CH:11]=1
Reactant: Cl
Reactant: FC(F)(F)Oc1ccccc1
Reactant: C1COOOC1
Agent: [Cl-]
Agent: [Zn+2]
Product: FC(F)(F)Oc1ccc(CCl)cc1
Temperature: 25 °C

Procedure:
A mixture of trioxane (355 mg), zinc chloride (340 mg) and trifluoromethoxybenzene (600 mg) is heated at 73° C. while hydrogen chloride gas is bubbled through the reaction mixture. The reaction is cooled to room temperature and diluted with ether. The organic phase is washed with saturated sodium carbonate solution and water. Removal of the solvents gives the product as a colorless liquid (1.42 g).
Reaction SMILES: Br[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[Cl:8][C:9]1[CH:16]=[C:15]([C:17]([F:20])([F:19])[F:18])[CH:14]=[C:13]([Cl:21])[C:10]=1[CH:11]=[O:12].COB(OC)OC.Cl>O1CCCC1.[Zn].C(O)(=O)C>[Cl:8][C:9]1[CH:16]=[C:15]([C:17]([F:19])([F:20])[F:18])[CH:14]=[C:13]([Cl:21])[C:10]=1[CH:11]([OH:12])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4]
Reactant: O=Cc1c(Cl)cc(C(F)(F)F)cc1Cl
Reactant: CCOC(=O)CBr
Agent: COB(OC)OC
Agent: Cl
Agent: [Zn]
Solvent: C1CCOC1
Solvent: CC(=O)O
Product: CCOC(=O)CC(O)c1c(Cl)cc(C(F)(F)F)cc1Cl
Temperature: 25 °C

Procedure:
Ethyl bromoacetate (13.7 ml) was added to a suspension of 30.0 g of 2,6-dichloro-4-trifluoromethylbenzaldehyde (7), 50 ml of trimethoxyborane and 8.5 g of zinc powder in 50 ml of anhydrous tetrahydrofuran with vigorous stirring at room temperature, and the mixture was stirred overnight. The reaction mixture was poured into a mixture of 100 ml of 10% hydrochloric acid and 10 ml of acetic acid, and the resulting mixture was filtered through Celite. The aqueous filtrate was neutralized with a 5% aqueous solution of sodium hydrogencarbonate, followed by extraction with ethyl acetate, drying over anhydrous magnesium sulfate and concentration under reduced pressure, affording 40.7 g of the desired compound in the form of a pale green oil (quantitative crude yield).
Reaction SMILES: [CH2:1](Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[C:15]1([N:21]2[C:29](=[O:30])[C:28]3[C@@H:27]4[C:31]([CH3:33])([CH3:32])[C@@:24]([CH3:34])([CH2:25][CH2:26]4)[C:23]=3[NH:22]2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>CC(C)=O.CO>[CH2:1]([N:22]1[C:23]2[C@@:24]3([CH3:34])[C:31]([CH3:33])([CH3:32])[C@H:27]([CH2:26][CH2:25]3)[C:28]=2[C:29](=[O:30])[N:21]1[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC1(C)[C@@H]2CC[C@@]1(C)c1[nH]n(-c3ccccc3)c(=O)c12
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: CO
Product: CC1(C)[C@@H]2CC[C@@]1(C)c1c2c(=O)n(-c2ccccc2)n1Cc1ccccc1
Temperature: 25 °C
Yield: 4 %

Procedure:
A mixture of benzyl bromide (1.54 mL, 13.0 mmol), potassium carbonate (3.58 g, 25.9 mmol), and (4S,7R)-2-phenyl-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 6; 1.74 g, 6.5 mmol) in acetone (20 mL) and methanol (3 mL) was heated at reflux overnight, then a further portion of benzyl bromide (0.75 mL, 6.3 mmol) was added and the reaction mixture was allowed to stir at room temperature over the weekend. The solvent was evaporated and the residue was partitioned between water and dichloromethane. The organic layer was evaporated and the residue was chromatographed (0-50% ethyl acetate/hexanes), and recrystallized from ethyl acetate/hexanes to give (4S,7R)-1-benzyl-7,8,8-trimethyl-2-phenyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (94 mg, 3%) as a white solid. APCI-MS (M+H) 359.
Reaction SMILES: [C:1]1(=[O:19])[N:5]([CH2:6][CH2:7][CH2:8][C:9]2[N:10]=[CH:11][NH:12][CH:13]=2)[C:4](=[O:14])[C:3]2=[CH:15][CH:16]=[CH:17][CH:18]=[C:2]12.F[C:21]1[CH:34]=[CH:33][C:24]([C:25]([CH:27]([CH3:32])[CH2:28][C:29]([OH:31])=[O:30])=[O:26])=[CH:23][CH:22]=1>>[C:4]1(=[O:14])[N:5]([CH2:6][CH2:7][CH2:8][C:9]2[N:10]=[CH:11][N:12]([C:21]3[CH:34]=[CH:33][C:24]([C:25]([CH:27]([CH3:32])[CH2:28][C:29]([OH:31])=[O:30])=[O:26])=[CH:23][CH:22]=3)[CH:13]=2)[C:1](=[O:19])[C:2]2=[CH:18][CH:17]=[CH:16][CH:15]=[C:3]12
Reactant: CC(CC(=O)O)C(=O)c1ccc(F)cc1
Reactant: O=C1c2ccccc2C(=O)N1CCCc1c[nH]cn1
Product: CC(CC(=O)O)C(=O)c1ccc(-n2cnc(CCCN3C(=O)c4ccccc4C3=O)c2)cc1

Procedure:
Prepared by a method analogous to that of Example (a) from 2.6 g (10.2 mmol) of 4-(3-phthalimidopropyl)-imidazole and 2.2 g (10.5 mmol) of 3-(4-fluorobenzoyl)-butyric acid. 3.4 g (75%) of a brownish, viscous oil is obtained which is used without further purification for the next stage.
Reaction SMILES: [OH:1][C@H:2]1[CH2:6][CH2:5][N:4]([CH2:7][C:8]#[CH:9])[C:3]1=[O:10].[C:11](OC(=O)C)(=[O:13])[CH3:12].N1C=CC=CC=1.C(Cl)Cl>CN(C)C1C=CN=CC=1.CO>[C:11]([O:1][C@H:2]1[CH2:6][CH2:5][N:4]([CH2:7][C:8]#[CH:9])[C:3]1=[O:10])(=[O:13])[CH3:12]
Reactant: C#CCN1CC[C@H](O)C1=O
Reactant: CC(=O)OC(C)=O
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Solvent: CO
Solvent: ClCCl
Product: C#CCN1CC[C@H](OC(C)=O)C1=O
Reaction time: 0.33 h

Procedure:
A solution of 4.3 g of (S)-3-hydroxy-1-(2-propynyl)-2-pyrrolidinone, 10.6 ml of acetic anhydride, 0.6 ml of pyridine, 0.1 g of 4-(dimethylamino)pyridine and 85 ml of methylene chloride is stirred at room temperature for 18 hours. Twenty-five ml of methyl alcohol is added and the reaction stirred for 20 minutes. The mixture is washed with 1N hydrochloric acid and saturated sodium bicarbonate. The organic layer is dried, passed thorough a pad of hydrous magnesium silicate and concentrated in vacuo to give 4.9 g of the desired product as a pale yellow oil.
Reaction SMILES: [CH3:1][O:2][C@@H:3]([C@@H:33]([N:38]([CH3:46])[C:39](=[O:45])[C@H:40]([CH:42]([CH3:44])[CH3:43])[NH2:41])[C@@H:34]([CH3:37])[CH2:35][CH3:36])[CH2:4][C:5]([N:7]1[CH2:11][CH2:10][CH2:9][C@H:8]1[C@H:12]([O:31][CH3:32])[C@@H:13]([CH3:30])[C:14](=[O:29])[NH:15][C@H:16]([C:24]1[S:25][CH:26]=[CH:27][N:28]=1)[CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:6].[C:47]([O:51][C:52]([N:54]([CH3:61])[C:55]([CH3:60])([C:57](O)=[O:58])[CH3:56])=[O:53])([CH3:50])([CH3:49])[CH3:48].C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl>[C:47]([O:51][C:52]([N:54]([CH3:61])[C:55]([CH3:60])([C:57]([NH:41][C@H:40]([C:39]([N:38]([C@@H:33]([C@@H:34]([CH3:37])[CH2:35][CH3:36])[C@H:3]([O:2][CH3:1])[CH2:4][C:5]([N:7]1[CH2:11][CH2:10][CH2:9][C@H:8]1[C@H:12]([O:31][CH3:32])[C@@H:13]([CH3:30])[C:14](=[O:29])[NH:15][C@H:16]([C:24]1[S:25][CH:26]=[CH:27][N:28]=1)[CH2:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)=[O:6])[CH3:46])=[O:45])[CH:42]([CH3:44])[CH3:43])=[O:58])[CH3:56])=[O:53])([CH3:50])([CH3:49])[CH3:48]
Reactant: CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@@H](Cc1ccccc1)c1nccs1)OC)N(C)C(=O)[C@@H](N)C(C)C
Reactant: CN(C(=O)OC(C)(C)C)C(C)(C)C(=O)O
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@@H](Cc1ccccc1)c1nccs1)OC)N(C)C(=O)[C@@H](NC(=O)C(C)(C)N(C)C(=O)OC(C)(C)C)C(C)C
Reaction time: 8 h
Yield: 55.5 %

Procedure:
To a mixture of #86 (80.3 mg, 0.122 mmol, 1 eq.) in dichloromethane (4 mL, 0.03 M) was added N-(tert-butoxycarbonyl)-N,2-dimethylalanine (29.1 mg, 0.134 mmol, 1.1 eq.) followed by diisopropylethylamine (64 μL, 0.365 mmol, 3 eq.) and HATU (71.7 mg, 0.183 mmol, 1.5 eq.) After stirring overnight, the reaction mixture was concentrated in vacuo. The residue was taken up in ethyl acetate (6 mL) and washed with 1 M aqueous hydrochloric acid solution (2×2 mL) and with brine. The organic solvent was dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was taken up in dichloromethane and filtered; the filtrate was concentrated in vacuo onto silica and purified by silica gel chromatography (Gradient: 0% to 50% acetone in heptane) to afford #87 (58 mg, 50%) as a white solid. LC-MS: m/z 857.7 [M+H+], 879.7 [M+Na+], retention time=0.99 minute; 1H NMR (400 MHz, DMSO-d6), presumed to be a mixture of rotamers, characteristic signals: δ [8.64 (br d, J=8 Hz) and 8.87 (br d, J=9 Hz), total 1H], [7.77 (d, J=3.3 Hz) and 7.80 (d, J=3.3 Hz), total 1H], [7.63 (d, J=3.2 Hz) and 7.66 (d, J=3.2 Hz), total 1H], 7.13-7.31 (m, 5H), [6.95 (br d, J=8 Hz) and 7.06 (br d, J=8 Hz), total 1H], 5.35-5.42 and 5.51-5.58 (2 m, total 1H), 3.15, 3.19, 3.20 and 3.26 (4 s, total 6H), 2.94 and 3.03 (2 br s, total 3H), 2.83 and 2.84 (2 s, total 3H), [1.05 (d, J=6.7 Hz) and 1.11 (d, J=6.7 Hz), total 3H].
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[C:5]([OH:10])=[CH:4][C:3]=1[C:11](=O)[CH3:12].Cl.[N+:15]([C:18]1[CH:26]=[CH:25][C:21]([CH2:22][O:23][NH2:24])=[CH:20][CH:19]=1)([O-:17])=[O:16].N1C=CN=C1.C(OCC)(=O)C.CCCCCC>CCO>[N+:15]([C:18]1[CH:19]=[CH:20][C:21]([CH2:22][O:23]/[N:24]=[C:11](/[C:3]2[CH:4]=[C:5]([OH:10])[C:6]([O:8][CH3:9])=[CH:7][C:2]=2[Br:1])\[CH3:12])=[CH:25][CH:26]=1)([O-:17])=[O:16]
Reactant: COc1cc(Br)c(C(C)=O)cc1O
Reactant: NOCc1ccc([N+](=O)[O-])cc1
Agent: Cl
Agent: c1c[nH]cn1
Solvent: CCOC(C)=O
Solvent: CCO
Solvent: CCCCCC
Product: COc1cc(Br)c(/C(C)=N/OCc2ccc([N+](=O)[O-])cc2)cc1O

Procedure:
A magnetically stirred solution of ketone 39 (162 mg, 0.661 mmol) in EtOH (2.0 mL) was treated with compound 19 (271 mg, 1.32 mmol) and imidazole (68 mg, 0.999 mmol) then the resulting mixture stirred at reflux for 2 h before being cooled and concentrated under reduced pressure. The ensuing residue was partitioned between CH2Cl2 (10 mL) and H2O (10 mL) and the separated aqueous fraction extracted with CH2Cl2 (1×10 ml). The combined organic fractions were then dried (MgSO4), filtered and concentrated under reduced pressure. The resulting mixture was subjected to flash chromatography (15:85 v/v ethyl acetate/hexane) to afford a ca. 3:1 mixture of the E- and Z-isomeric foams of the title compound CP302108 (229 mg, 88%) as a pale-yellow solid, Rf 0.5 in 1:1 v/v ethyl acetate/hexane. Recrystallisation of this material (twice from isopropanol) afforded the major isomer, CP302108-major, as a pale-yellow solid, m.p. 136.8-138.4° C.
Reaction SMILES: [CH3:1][C:2]1([CH3:14])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:10]=[N:11][NH:12][CH:13]=2)[O:3]1.CS(O[CH:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1)(=O)=O>C(#N)C>[O:23]1[CH2:24][CH2:25][CH:20]([N:12]2[CH:13]=[C:9]([B:4]3[O:5][C:6]([CH3:7])([CH3:8])[C:2]([CH3:14])([CH3:1])[O:3]3)[CH:10]=[N:11]2)[CH2:21][CH2:22]1
Reactant: CC1(C)OB(c2cn[nH]c2)OC1(C)C
Reactant: CS(=O)(=O)OC1CCOCC1
Solvent: CC#N
Product: CC1(C)OB(c2cnn(C3CCOCC3)c2)OC1(C)C
Temperature: 90 °C
Reaction time: 2 h
Yield: 81.7 %

Procedure:
A mixture of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (30.0 mg, 0.154 mmol), and tetrahydro-2H-pyran-4-yl methanesulfonate (0.150 g, 0.460 mmol) in acetonitrile (1.0 mL) was stirred at 90° C. for 2 hours. The reaction was quenched with water, extracted with ethyl acetate. The combined organic layer was dried over MgSO4, then filtered and concentrated under reduced pressure to afford the desired product (35 mg, 80%), which was used directly in the next step without further purification. LCMS calculated for C14H24BN2O3 (M+H)+: m/z=279.2. Found: 279.2.
Reaction SMILES: Cl.[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1[O:14][CH3:15])[C:10](=[CH:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[C:19]([O:25][CH3:26])[CH:18]=1)[NH:9][CH2:8][CH2:7]2.N1C=CC=CC=1.[CH:33]1([C:36](Cl)=[O:37])[CH2:35][CH2:34]1>O>[CH:33]1([C:36]([N:9]2[CH2:8][CH2:7][C:6]3[C:11](=[CH:12][C:13]([O:14][CH3:15])=[C:4]([O:3][CH3:2])[CH:5]=3)/[C:10]/2=[CH:16]/[C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[C:19]([O:25][CH3:26])[CH:18]=2)=[O:37])[CH2:35][CH2:34]1
Reactant: O=C(Cl)C1CC1
Reactant: COc1ccc(C=C2NCCc3cc(OC)c(OC)cc32)cc1OC
Agent: Cl
Solvent: O
Solvent: c1ccncc1
Product: COc1ccc(/C=C2/c3cc(OC)c(OC)cc3CCN2C(=O)C2CC2)cc1OC

Procedure:
To a suspension of 6 parts of 3,4-dihydro-6,7-dimethoxy-1-[(3,4-dimethoxyphenyl)methylene]isoquinoline hydrochloride in 40 parts of pyridine is added 6 parts of cyclopropanecarbonyl chloride. The resultant mixture is stirred at room temperatures for 18 hours, then poured into 500 parts of water. The mixture thus obtained is extracted with chloroform. The chloroform extract is washed with 5% hydrochloric acid, dried over anhydrous sodium sulfate, and stripped of solvent by vacuum distillation. The residue is crystallized from a mixture of ethyl acetate and dichloromethane to give (Z)-2-cyclopropylcarbonyl-1,2,3,4-tetrahydro-6,7-dimethoxy-1-[(3,4-dimethoxyphenyl)methylene]isoquinoline melting at 148°-151°.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:12][CH2:13][N:14]1[CH2:18][CH2:17][CH2:16][CH2:15]1)[C:7]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[C:6]2[CH3:24])#[CH:2].[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]2[CH:33]=[CH:34][C:35](I)=[N:36][CH:37]=2)=[CH:28][CH:27]=1.N1CCCCC1>C1COCC1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[Cl:25][C:26]1[CH:27]=[CH:28][C:29]([C:32]2[CH:33]=[CH:34][C:35]([C:2]#[C:1][C:3]3[CH:4]=[C:5]4[C:9](=[CH:10][CH:11]=3)[N:8]([CH2:12][CH2:13][N:14]3[CH2:15][CH2:16][CH2:17][CH2:18]3)[C:7]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[C:6]4[CH3:24])=[N:36][CH:37]=2)=[CH:30][CH:31]=1
Reactant: C#Cc1ccc2c(c1)c(C)c(C(=O)OCC)n2CCN1CCCC1
Reactant: Clc1ccc(-c2ccc(I)nc2)cc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: O
Solvent: C1CCNCC1
Solvent: C1CCOC1
Product: CCOC(=O)c1c(C)c2cc(C#Cc3ccc(-c4ccc(Cl)cc4)cn3)ccc2n1CCN1CCCC1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
Under an argon atmosphere 11 mg (0.02 mmol) Pd(PPh3)2Cl2 and 3 mg (0.02 mmol) CuI are added to a solution of 250 mg (0.77 mmol) ethyl 5-ethynyl-3-methyl-1-(2-pyrrolidin-1-yl-ethyl)-1H-indole-2-carboxylate and 243 mg (0.77 mmol) 5-(4-chloro-phenyl)-2-iodo-pyridine in 1.52 mL (15.4 mmol) piperidine and 25 mL THF and the reaction mixture is stirred for 4 h at RT. It is diluted with water, extracted exhaustively with EtOAc, the combined organic phases are washed with water and saturated NaCl solution and dried over Na2SO4. After the desiccant and solvent have been eliminated the residue is purified first by chromatography (silica gel, cyc/EtOAc 2:1) and then by HPLC.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]=[CH:9][C:10]2[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=2[CH2:12][Br:13])=[CH:4][CH:3]=1.[C:18]1([P:24]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>C1(C)C(C)=CC=CC=1>[Br-:13].[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]=[CH:9][C:10]2[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=2[CH2:12][P+:24]([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)=[CH:4][CH:3]=1
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Reactant: Fc1ccc(C=Cc2ccccc2CBr)cc1
Solvent: Cc1ccccc1C
Product: Fc1ccc(C=Cc2ccccc2C[P+](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Product: [Br-]
Reaction time: 0.5 h

Procedure:
37.47 g (0.15 mol) of 2-(2-(4-fluorophenyl)ethenyl)benzyl bromide (Example 9 g) were dissolved together with 39.3 g (0.15 mol) of triphenylphosphine in 220 ml of xylene, and the solution was heated under reflux for about 3-6 hours. After about 1/2 hour, the insoluble phosphonium salt which was formed began to separate out. The course of the reaction was followed by thin-layer chromatography on silica gel plates in CH3OH/CH2CL2 =1/1. After the reaction was complete, the mixture was cooled, the solid salt was filtered off with suction, washed with diethyl ether and dried at 150° C. in vacuo.
Reaction SMILES: C(C1C=C(C2ON=C(C3C=C(C)C(OCC(O)CNC(=O)CO)=C(C)C=3)N=2)C=CC=1)=O.[CH:32]([C:34]1[CH:35]=[C:36]([CH:40]=[CH:41][C:42]=1[CH3:43])[C:37]([OH:39])=O)=[O:33].[CH2:44]([C:46]1[CH:61]=[C:60]([C:62](=[NH:65])[NH:63]O)[CH:59]=[C:58]([CH3:66])[C:47]=1[O:48][CH2:49][C@@H:50]([OH:57])[CH2:51][NH:52][C:53](=[O:56])[CH2:54][OH:55])[CH3:45]>>[CH2:44]([C:46]1[CH:61]=[C:60]([C:62]2[N:65]=[C:37]([C:36]3[CH:40]=[CH:41][C:42]([CH3:43])=[C:34]([CH:32]=[O:33])[CH:35]=3)[O:39][N:63]=2)[CH:59]=[C:58]([CH3:66])[C:47]=1[O:48][CH2:49][C@@H:50]([OH:57])[CH2:51][NH:52][C:53](=[O:56])[CH2:54][OH:55])[CH3:45]
Reactant: CCc1cc(C(=N)NO)cc(C)c1OC[C@@H](O)CNC(=O)CO
Reactant: Cc1ccc(C(=O)O)cc1C=O
Agent: Cc1cc(-c2noc(-c3cccc(C=O)c3)n2)cc(C)c1OCC(O)CNC(=O)CO
Product: CCc1cc(-c2noc(-c3ccc(C)c(C=O)c3)n2)cc(C)c1OC[C@@H](O)CNC(=O)CO
Yield: 43.4 %

Procedure:
The title compound (405 mg) is prepared in analogy to rac-N-(3-{4-[5-(3-formyl-phenyl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide, starting from 3-formyl-4-methyl-benzoic acid (338 mg, 2.06 mmol) and N—((S)-3-[2-ethyl-4-(N-hydroxycarbamimidoyl)-6-methyl-phenoxy]-2-hydroxy-propyl)-2-hydroxy-acetamide (670 mg, 2.06 mmol). LC-MS**: tR=0.68 min; [M+1]+=454.17; 1H NMR (D6-DMSO): δ 1.23 (t, J=7.5 Hz, 3H), 2.35 (s, 3H), 2.70-2.78 (m, 5H), 3.21-3.29 (m, 1H), 3.39-3.48 (m, 1H), 3.71-3.80 (m, 2H), 3.84 (d, J=5.5 Hz, 2H), 3.93-4.01 (m, 1H), 5.32 (d, J=5.3 Hz, 1H), 5.56 (t, J=5.5 Hz, 1H), 7.66 (d, J=8.3 Hz, 1H), 7.71 (t, J=5.5 Hz, 1H), 7.81 (s, 2H), 8.33 (dd, J=8.0, 1.8 Hz, 1H), 8.60 (d, J=1.8 Hz, 1H), 10.37 (s, 1H).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][S:4](=[O:8])(=[O:7])[CH2:3][CH:2]1[C:9]([O:11][CH3:12])=[O:10].[C:13]([NH:20][CH2:21][CH:22]=O)([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH3:17][C:16]([O:15][C:13]([NH:20][CH2:21][CH2:22][N:1]1[CH2:6][CH2:5][S:4](=[O:7])(=[O:8])[CH2:3][CH:2]1[C:9]([O:11][CH3:12])=[O:10])=[O:14])([CH3:19])[CH3:18]
Reactant: CC(C)(C)OC(=O)NCC=O
Reactant: COC(=O)C1CS(=O)(=O)CCN1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCCl
Product: COC(=O)C1CS(=O)(=O)CCN1CCNC(=O)OC(C)(C)C
Temperature: 25 °C

Procedure:
To a stirred solution of methyl 3-thiomorpholinecarboxylate 1,1-dioxide (D16; 1.08 g, 5.6 mmol) in 14 ml of anhydrous 1,2-dichloroethane was added N-boc-2-aminoacetaldehyde (1.1 g, 6.7 mmol) and acetic acid (0.316 ml, 5.6 mmol). After 30 min. sodium triacetoxyborohydride (1.78 g, 8.4 mmol) was added and the solution stirred at room temperature. Additional aliquots of N-boc-2-aminoacetaldehyde and sodium triacetoxyborohydride (1.0 g, 4.7 mmol) were added and the reaction continued overnight.
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([CH:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1)=[O:11].C(C(O)=O)(F)(F)F.[CH3:25][O:26][C:27]1[CH:32]=[CH:31][C:30]([CH2:33][CH2:34]Br)=[CH:29][CH:28]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([CH:12]1[CH2:17][CH2:16][N:15]([CH2:34][CH2:33][C:30]2[CH:31]=[CH:32][C:27]([O:26][CH3:25])=[CH:28][CH:29]=2)[CH2:14][CH2:13]1)=[O:11]
Reactant: COc1ccc(CCBr)cc1
Reactant: O=C(c1nc2ccccc2s1)C1CCNCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O=C(O)C(F)(F)F
Solvent: CN(C)C=O
Product: COc1ccc(CCN2CCC(C(=O)c3nc4ccccc4s3)CC2)cc1
Temperature: 25 °C

Procedure:
Mix (2-benzothiazolyl)(4-piperidinyl)methanone.CF3CO2H (331 g, 9.19 mmol), 2-(4-methoxyphenyl)ethyl bromide (2.07 g, 9.64 mmol), potassium carbonate (3.33 g, 24.mmol and dimethylformamide (35 mL) and heat at 90° C. overnight. Cool to room temperature and partition between a 2:1 mixture of ethyl acetate/toluene and water. Separate the aqueous phase and wash the organic phase with water and brine. Dry (MgSO4) and evaporate the solvent in vacuo. Purify by chromatography (30% ethyl acetate/hexane) and recrystallize (cyclohexane) to give the title compound as a tan powder; mp 119°-20° C.
Reaction SMILES: Br[CH2:2][CH2:3][O:4][N:5]=[C:6]([C:12]1([O:17][CH2:16][CH2:15][O:14]1)[CH3:13])[C:7]([O:9][CH2:10][CH3:11])=[O:8].[CH3:18]C(C)([O-])C.[K+]>CN(C)C=O>[CH:3]1([O:4][N:5]=[C:6]([C:12]2([O:17][CH2:16][CH2:15][O:14]2)[CH3:13])[C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:18][CH2:2]1
Reactant: CCOC(=O)C(=NOCCBr)C1(C)OCCO1
Reactant: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)C(=NOC1CC1)C1(C)OCCO1
Temperature: 0 °C
Yield: 38.2 %

Procedure:
To a solution of ethyl 2-(2-bromoethoxyimino)-3,3-ethylenedioxybutyrate (syn isomer)(50 g) in N,N-dimethylformamide (100 ml) was portionwise added potassium tert-butoxide (21 g) under -10° C. and the resulted mixture was allowed to be stirred under ice-cooling for 20 minutes. The mixture was poured into ice-water (400 ml) and extracted with methylene chloride (200 ml). The extract was washed with water (200 ml×3) and saturated aqueous solution of sodium chloride (400 ml) successively, dried over magnesium sulfate, and added methylene iodide (16.2 ml). To the solution was dropwise added a 35% (W/W) solution of diethylzinc in cyclohexane (55 ml) under reflux during 40 minutes under nitrogen. atmosphere. After refluxed for 18 hours, the mixture was poured into ice-water (400 ml) and adjusted to 40 with 1N hydrochloric acid. The organic layer was separated, washed with an aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride successively, dried over magnesium sulfate, and concentrated in vacuo. The residue was subjected to column chromatography on silica gel (50 g) using diisopropyl ether as an eluent to give ethyl 2-cyclopropyloxyimino-3,3-ethylenedioxybutyrate (syn isomer)(15 g), the physical data of which were identical to those of the compound prepared in Preparation 10.
Reaction SMILES: [S:1]([O-:5])([O-:4])(=[O:3])=[O:2].[K+:6].[K+].[Cl:8]Cl>>[S:1]([O-:5])([O-:4])(=[O:3])=[O:2].[K+:6].[K+:6].[Cl-:8].[K+:6].[S:1](=[O:3])(=[O:2])([OH:5])[OH:4]
Reactant: ClCl
Agent: O=S(=O)([O-])[O-]
Agent: [K+]
Product: O=S(=O)(O)O
Product: [Cl-]

Procedure:
An object of this invention is to provide a process for preparing a dry-converted potassium sulfate having a residual chlorine content of less than 3.5%, particularly of less than 2.0% from a dry-converted potassium sulfate obtained under the condition of a potassium chloride to sulfuric acid molar ratio of from 2.0 to 2.2.