Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:13]=[C:12]([O:14][CH:15]([CH3:17])[CH3:16])[NH:11][N:10]=2)[C:5]([N+:18]([O-:20])=[O:19])=[CH:4][CH:3]=1.[F:21][C:22]1[CH:27]=[CH:26][C:25]([C@@H:28]([NH2:30])[CH3:29])=[CH:24][CH:23]=1.CCN(C(C)C)C(C)C>CCCCO>[F:21][C:22]1[CH:27]=[CH:26][C:25]([C@@H:28]([NH:30][C:2]2[N:7]=[C:6]([NH:8][C:9]3[CH:13]=[C:12]([O:14][CH:15]([CH3:17])[CH3:16])[NH:11][N:10]=3)[C:5]([N+:18]([O-:20])=[O:19])=[CH:4][CH:3]=2)[CH3:29])=[CH:24][CH:23]=1
Reactant: C[C@H](N)c1ccc(F)cc1
Reactant: CC(C)Oc1cc(Nc2nc(Cl)ccc2[N+](=O)[O-])n[nH]1
Solvent: CCN(C(C)C)C(C)C
Solvent: CCCCO
Product: CC(C)Oc1cc(Nc2nc(N[C@@H](C)c3ccc(F)cc3)ccc2[N+](=O)[O-])n[nH]1
Temperature: 165 °C
Yield: 97.6 %

Procedure:
A mixture of 6-chloro-N-(5-isopropoxy-1H-pyrazol-3-yl)-3-nitropyridin-2-amine (Method 28, 0.33 g, 1.1 mmol), (S)-1-(4-fluoro-phenyl)-ethylamine (0.16 g, 1.2 mmol) and DIEA (0.21 ml, 1.2 mmol) in n-BuOH (3 ml) was heated in a sealed tube at 165° C. for 4 hours. The solvent was removed under reduced pressure and the residue was purified by column chromatography (hexane-EtOAc=1:1) to give the title compound as a yellow solid (0.43 g, 97%). 1H NMR (400 MHz) δ 12.09, 12.05 & 11.64 (s, 1H), 10.94, 10.87 & 10.72 (s, 1H), 8.98, 8.76 & 8.70 (d, J=7.6 Hz, 1H), 8.16 & 8.11 (d, J=9.6 Hz, 1H), 7.40-7.33 (m, 2H), 7.22-7.10 (m, 2H), 6.25 & 6.04 (d, J=9.6 Hz, 1H), 6.23 & 5.86 (d, J=13.6 Hz, 1H), 5.31, 5.21 & 4.89 (m, 1H), 4.71, 4.59 & 4.27 (m, 1H), 1.52 (m, 3H), 1.26 (m, 6H). MS: Calcd.: 400. Found: [M+H]+ 401.
Reaction SMILES: C(N(CC)CC)C.[C:8]([NH:11][C:12](=[CH:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:13]([OH:15])=[O:14])(=[O:10])[CH3:9].[H][H]>CO>[C:8]([NH:11][C@@H:12]([C:13]([OH:15])=[O:14])[CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)(=[O:10])[CH3:9]
Reactant: CC(=O)NC(=Cc1ccccc1)C(=O)O
Reactant: [H][H]
Solvent: CCN(CC)CC
Solvent: CO
Product: CC(=O)N[C@H](Cc1ccccc1)C(=O)O
Temperature: 40 °C
Reaction time: 22 h

Procedure:
The atmosphere in a 25 mL-recovery flask was substituted with nitrogen, and 3 mL of deoxygenized methanol and triethylamine (20.9 μL, 0.15 mmol) were added to the flask as the reaction solvent. α-Acetamidocinnamic acid (0.20 g, 0.98 mmol) and [Rh(CLPL-S)(COD)]BF4 (3.95 mg, 0.0049 mmol) were weighed in a 50 mL-Pyrex (registered trade name) test tube for autoclaving, the tube was put into an autoclave together with a stirrer in the tube, and the atmosphere in the autoclave was substituted with nitrogen. The reaction solvent in a volume of 2 mL was added to the mixture, the atmosphere in the autoclave was sufficiently substituted with hydrogen, and then pressurized with 2 MPa of hydrogen, and the reaction mixture was stirred at 40° C. for 22 hours. After 22 hours, the atmosphere in the autoclave was returned to ordinary pressure, and the reaction mixture was concentrated in an evaporator. The concentrated residue was added with 5 mL of 2 M aqueous sodium hydroxide for dissolution, and the solution was washed with 5 mL of ethyl acetate. The aqueous layer was separated, and added with diluted hydrochloric acid until pH of the aqueous layer became lower than 2, and the produced oil was extracted with 10 mL of ethyl acetate. The organic layer was concentrated in an evaporator to obtain (R)-N-acetylphenylalanine quantitatively.
Reaction SMILES: Br[CH:2]([CH3:4])[CH3:3].[Br:5][C:6]1[C:7](=[O:16])[NH:8][CH:9]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:11]=1>CCCCCC.C(=O)([O-])[O-].[Ag+2]>[Br:5][C:6]1[C:7]([O:16][CH:2]([CH3:4])[CH3:3])=[N:8][CH:9]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:11]=1
Reactant: CC(C)Br
Reactant: O=c1[nH]cc(C(F)(F)F)cc1Br
Agent: [Ag+2]
Agent: O=C([O-])[O-]
Solvent: CCCCCC
Product: CC(C)Oc1ncc(C(F)(F)F)cc1Br
Temperature: 50 °C
Reaction time: 14 h
Yield: 71.3 %

Procedure:
2-Bromopropane (0.78 ml, 8.3 mmol) was added to a stirred suspension of 3-bromo-5-trifluoromethyl-2(1H)-pyridone (2.0 g, 8.3 mmol) and silver carbonate (1.16 g, 4.2 mmol) in hexane (40 ml) and the mixture stirred at 50° C. for 14 h, then at reflux for 3 h. More 2-bromopropane (0.78 ml) was added and reflux resumed for a further 3 h. On cooling, the mixture was filtered, the filtrate diluted with hexane (100 ml) and washed with water (50 ml). The organic layer was dried (Na2SO4), evaporated, and the residual oil subjected to column chromatography over silica gel, eluting with ethyl acetate/hexane (5:95) to leave the product as a colourless oil (1.68 g).
Reaction SMILES: [Br:1][C:2]1[CH:18]=[C:17](/[CH:19]=[CH:20]/[CH:21]([C:26]2[CH:31]=[C:30]([Cl:32])[C:29]([Cl:33])=[C:28]([Cl:34])[CH:27]=2)[C:22]([F:25])([F:24])[F:23])[CH:16]=[CH:15][C:3]=1[C:4]([NH:6][CH2:7][C:8]([O:10]C(C)(C)C)=[O:9])=[O:5].C(O)(C(F)(F)F)=O>C(Cl)Cl>[Br:1][C:2]1[CH:18]=[C:17](/[CH:19]=[CH:20]/[CH:21]([C:26]2[CH:31]=[C:30]([Cl:32])[C:29]([Cl:33])=[C:28]([Cl:34])[CH:27]=2)[C:22]([F:24])([F:25])[F:23])[CH:16]=[CH:15][C:3]=1[C:4]([NH:6][CH2:7][C:8]([OH:10])=[O:9])=[O:5]
Reactant: CC(C)(C)OC(=O)CNC(=O)c1ccc(/C=C/C(c2cc(Cl)c(Cl)c(Cl)c2)C(F)(F)F)cc1Br
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C(O)CNC(=O)c1ccc(/C=C/C(c2cc(Cl)c(Cl)c(Cl)c2)C(F)(F)F)cc1Br
Temperature: 25 °C
Reaction time: 1 h
Yield: 77.4 %

Procedure:
To a stirred solution of (E)-tert-butyl 2-(2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamido)acetate (440 mg, 0.734 mmol) in DCM (36.0 ml), was added TFA (4.0 mL) and the reaction mixture was stirred at RT for 1 h. The reaction mixture was concentrated under reduced pressure to obtain residue which was washed with n-pentane to afford the title compound as an off-white solid (310 mg, 78%): 1H NMR (400 MHz, CDCl3) δ 13.0 (s, 1H), 8.75 (t, J=5.7 Hz, 1H), 7.93 (m, 2H), 7.62 (d, J=7.5 Hz, 1H), 7.40 (d, J=8.1 Hz, 1H), 6.96 (dd, J=15.3, 9.3 Hz, 1H), 6.78 (d, J=15.3 Hz, 1H), 4.83 (m, 1H), 3.90 (d, J=5.7 Hz, 2H); ESIMS m/z 543.61 ([M+H]+); IR (thin film) 3429, 1635, 1114, 772 cm−1.
Reaction SMILES: [Cl:1][C:2]1[C:9]([CH3:10])=[C:8](F)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[NH2:12][C@@H:13]([C:17]([OH:19])=[O:18])[C@H:14]([CH3:16])[OH:15].C([O-])([O-])=O.[K+].[K+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CS(C)=O>[Cl:1][C:2]1[C:9]([CH3:10])=[C:8]([NH:12][C@H:13]([C@@H:14]([OH:15])[CH3:16])[C:17]([OH:19])=[O:18])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]
Reactant: Cc1c(F)ccc(C#N)c1Cl
Reactant: C[C@H](O)[C@@H](N)C(=O)O
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: Cc1c(N[C@@H](C(=O)O)[C@H](C)O)ccc(C#N)c1Cl
Temperature: 75 °C
Reaction time: 24 h

Procedure:
2-chloro-4-fluoro-3-methylbenzonitrile (CAS 796600-15-2, 45 g, 265.4 mmol) was mixed together with H-D-Thr-OH (37.92 g, 318.4 mmol) in DMSO (250 mL). K2CO3 (73.35 g, 530.7 mmol) was added to the reaction mixture and the reaction mixture stirred at 75° C. for 24 h. The reaction mixture was cooled to room temperature and poured slowly into a 10% citric acid solution and stirred for 10 min at room temperature. The solution was extracted with EtOAc several times to get the crude product. The crude product was chromatographed on silica gel with a gradient of hexanes/EtOAc and then with EtOAc, 100% to get the purified final product (39.0 g, 54%) 1H NMR (500 MHz, Acetone-d6, δ in ppm) 7.49 (d, 9 Hz, 1H), 6.70 (d, J=9 Hz, 1H), 5.38 (d, J=10 Hz, 1H), 4.47 (d, J=6 Hz, 1H), 4.25 (m, 1H), 2.34 (s, 3H), 1.33 (d, J=6 Hz, 3H).
Reaction SMILES: [Si:1](Cl)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].N1C=CN=C1.[C:14]1([C:20]2[C:29]([CH3:30])=[CH:28][C:27]3[C:22](=[C:23]([C@H:31]([OH:34])[CH2:32][OH:33])[CH:24]=[CH:25][CH:26]=3)[N:21]=2)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.O>CN(C)C=O>[C:14]1([C:20]2[C:29]([CH3:30])=[CH:28][C:27]3[C:22](=[C:23]([C@H:31]([OH:34])[CH2:32][O:33][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[CH:24]=[CH:25][CH:26]=3)[N:21]=2)[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: Cc1cc2cccc([C@H](O)CO)c2nc1-c1ccccc1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: O
Product: Cc1cc2cccc([C@H](O)CO[Si](C)(C)C(C)(C)C)c2nc1-c1ccccc1
Reaction time: 16 h
Yield: 92 %

Procedure:
3.7 g (24.3 mmol) of tert-butyldimethylsilyl chloride and 3.4 g of (50 mmol) of imidazole are added at ambient temperature to a solution of 6.5 g (23.2 mmol) of 2-phenyl-3-methyl-8-(1-(S),2-dihydroxyethyl)-quinoline in 200 ml of dimethylformamide. The reaction medium is stirred for 16 hours. After addition of 200 ml of distilled water, the reaction mixture is extracted with 3×200 ml of ethyl acetate. The organic phases are combined, washed with 300 ml of distilled water, dried over magnesium sulfate, filtered and concentrated under vacuum. The residue is purified by silica gel chromatography (eluent: ethyl acetate/cyclohexane to provide 8.4 g of 2-phenyl-3-methyl-8-(1-(S)-hydroxy-2-[tert-butyldimethylsilyloxy]ethyl)quinoline in the form of a colorless oil. (Yield: 85%)
Reaction SMILES: [CH:1]1([NH2:7])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:8]1([C:11]2[N:16]=[C:15]([C:17]([NH:19][C:20]3[CH:28]=[N:27][CH:26]=[CH:25][C:21]=3[C:22](O)=[O:23])=[O:18])[C:14]([NH:29][C:30]3[CH:31]=[N:32][CH:33]=[N:34][CH:35]=3)=[CH:13][CH:12]=2)[CH2:10][CH2:9]1>>[CH:1]1([NH:7][C:22]([C:21]2[CH:25]=[CH:26][N:27]=[CH:28][C:20]=2[NH:19][C:17]([C:15]2[C:14]([NH:29][C:30]3[CH:31]=[N:32][CH:33]=[N:34][CH:35]=3)=[CH:13][CH:12]=[C:11]([CH:8]3[CH2:10][CH2:9]3)[N:16]=2)=[O:18])=[O:23])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=C(O)c1ccncc1NC(=O)c1nc(C2CC2)ccc1Nc1cncnc1
Reactant: NC1CCCCC1
Product: O=C(NC1CCCCC1)c1ccncc1NC(=O)c1nc(C2CC2)ccc1Nc1cncnc1
Yield: 26 %

Procedure:
According to the general method described in step 3 of example 53, reaction of cyclohexylamine with 3-{[6-cyclopropyl-3-(pyrimidin-5-ylamino)-pyridine-2-carbonyl]-amino}-isonicotinic acid provided the title compound (26%) as amorphous yellow solid.
Reaction SMILES: C[O:2][C:3](=O)[C:4]1[CH:9]=[C:8]([O:10][CH3:11])[C:7]([O:12][CH3:13])=[CH:6][C:5]=1[NH:14][C:15](=O)[CH3:16].C([O-])(=O)C.[NH4+:23].C(O)(=O)C>O>[CH3:11][O:10][C:8]1[CH:9]=[C:4]2[C:5](=[CH:6][C:7]=1[O:12][CH3:13])[N:14]=[C:15]([CH3:16])[N:23]=[C:3]2[OH:2]
Reactant: [NH4+]
Reactant: COC(=O)c1cc(OC)c(OC)cc1NC(C)=O
Agent: CC(=O)[O-]
Solvent: CC(=O)O
Solvent: O
Product: COc1cc2nc(C)nc(O)c2cc1OC
Temperature: 25 °C

Procedure:
To the crude 2-acetylamino-4,5-dimethoxy-benzoic acid methyl ester obtained above was added ammonium acetate (7.98 g, 0.104 mol) and acetic acid (10 mL). The mixture was heated at reflux in a pressure tube until the formation of the desired cyclization product, as indicated by LC/MS: m/z 221 (M+H). After cooling to RT, the reaction mixture was diluted with water, and extracted with EtOAc 3 times. The combined organic phase was basified with aq. NaOH solution, and washed 3 times with EtOAc. The aqueous layer was then acidified with aq. HCl and extracted three times with EtOAc. The combined organic extract was dired over Na2SO4 and concentrated in vacuo, affording 6,7-dimethoxy-2-methyl-quinazolin-4-ol (0.15 g), which was used without further purification. LC/MS: m/z 221 (M+H).
Reaction SMILES: [OH:1][C:2]1[C:7]2[C:8]([CH3:16])=[C:9]([CH2:11][CH2:12][C:13]([OH:15])=[O:14])[O:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.[CH2:17](O)[CH3:18]>S(=O)(=O)(O)O>[OH:1][C:2]1[C:7]2[C:8]([CH3:16])=[C:9]([CH2:11][CH2:12][C:13]([O:15][CH2:17][CH3:18])=[O:14])[O:10][C:6]=2[CH:5]=[CH:4][CH:3]=1
Reactant: Cc1c(CCC(=O)O)oc2cccc(O)c12
Reactant: CCO
Agent: O=S(=O)(O)O
Product: CCOC(=O)CCc1oc2cccc(O)c2c1C
Reaction time: 18 h

Procedure:
A mixture of 3-(4-hydroxy-3-methylbenzofuran-2-yl)propionic acid (400 mg, 1.8 mmole) in 1% sulfuric acid in ethanol was kept at room temperature for 18 hours. The mixture was concentrated. The residue was taken up in diethyl ether, washed with water twice, dried with Na2SO4, filtered, concentrated and chromatographed to obtain 280 mg of the title compound, m.p. 61°-63° C.
Reaction SMILES: C[O:2][C:3](=O)[CH:4]=[CH:5][CH:6]=[CH:7][CH2:8][S:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=1)=[O:10].[NH2:20][OH:21].[OH-].[K+].CO>C1COCC1>[OH:21][NH:20][C:3](=[O:2])[CH:4]=[CH:5][CH:6]=[CH:7][CH2:8][S:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=1)=[O:10]
Reactant: COC(=O)C=CC=CCS(=O)c1ccc(OC)cc1
Reactant: NO
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: COc1ccc(S(=O)CC=CC=CC(=O)NO)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 34.3 %

Procedure:
To a solution of 6-(4-methoxybenzenesulfinyl)-hexa-2,4-dienoic acid methyl ester (0.32 g, 1.14 mmol) in distilled THF (6 mL) containing an aqueous solution of hydroxylamine (50%, 0.7 ml, 10.6 mmol) was added at 0° C. a solution of potassium hydroxide in methanol (1M, 1.8 ml, 1.8 mmol) over a period of 30 minutes. After stirring at 0° C. for 1 hour, distilled water (6 mL) was added and the mixture was made neutral by dropwise addition of concentrated hydrochloric acid (10 M) at 0° C. The aqueous solution was extracted with ethyl acetate (3×20 mL) and the combined extracts were dried over anhydrous MgSO4, and evaporated to dryness. The residue was recrystallised from acetone to give the title compound (0.11 g, 34%) as a pale brown powder, mp 145-147° C. (decomp).
Reaction SMILES: [C:1]([O:9]C)(=[O:8])[CH2:2][CH2:3][C:4]([O:6]C)=[O:5].C[O-].[Na+].[CH:14](=O)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>CO>[CH:14](=[C:3]([CH2:2][C:1]([OH:9])=[O:8])[C:4]([OH:6])=[O:5])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: COC(=O)CCC(=O)OC
Reactant: O=Cc1ccccc1
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: O=C(O)CC(=Cc1ccccc1)C(=O)O
Reaction time: 1 h

Procedure:
700 mmol of dimethyl succinate and then 20 ml of methanol are added to 290 mmol of sodium methylate dissolved in 80 ml of methanol. The mixture is brought to reflux, and 236 mmol of benzaldehyde are slowly added, followed by 20 ml of methanol. The mixture is maintained at reflux, with stirring, for one hour, and then 100 ml of methanol are distilled off. 120 ml of water and 120 ml of 10N sodium hydroxide solution are added to the concentrated reaction mixture. The removal of the methanol by distillation is continued. The residue is diluted with 150 ml of water. After the addition of dichloromethane, the diacid is precipitated by the slow addition of 12N hydrochloric acid. The diacid is filtered and washed with dicliloromethane and then with water. Drying yields the expected product.
Reaction SMILES: Br[C:2]1[C:3]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])=[CH:4][C:5]2[C:11]([CH3:13])([CH3:12])[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=2[CH:14]=1.[Li]CCCC.[C:26](=[O:28])=[O:27]>O1CCCC1>[CH2:15]([C:3]1[C:2]([C:26]([OH:28])=[O:27])=[CH:14][C:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:11]([CH3:13])([CH3:12])[C:5]=2[CH:4]=1)[CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]
Reactant: O=C=O
Reactant: CCCCCCc1cc2c(cc1Br)CCCCC2(C)C
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CCCCCCc1cc2c(cc1C(=O)O)CCCCC2(C)C
Reaction time: 0.67 h

Procedure:
This 3.21 g of 2-bromo-3-hexyl-5,5-dimethyl-6,7,8,9-tetrahydro-5H-benzocycloheptene were placed in 30 ml of abs. tetrahydrofuran under Ar and treated at -78° with 6.75 ml of 1.55M nBuLi (hexane) (1.1 eq.). The metal/halogen exchange was followed by gas chromatography (GC). After 40 min., a large excess of CO2 gas was introduced and the cooling bath was removed. After 10 min., the mixture was poured on to ice/NH4Cl solution, extracted with diethyl ether, washed with H2O, dried over Na2SO4 and the solvent was removed in a vacuum. Flash chromatography on SiO2 (hexane/ethyl acetate=8/2) yielded 2.26 g of 3-hexyl-5,5-dimethyl-6,7,8,9-tetrahydro-5H-benzocycloheptene-2-carboxylic acid as white crystals of m.p. 74-75°.
Reaction SMILES: Cl.[F:2][CH:3]([F:13])[O:4][C:5]1[CH:6]=[C:7]([NH:11][NH2:12])[CH:8]=[CH:9][CH:10]=1.[CH:14]([CH:16]([CH:22]=O)[C:17]([O:19][CH2:20][CH3:21])=[O:18])=O>C(O)C.CCCCC>[F:2][CH:3]([F:13])[O:4][C:5]1[CH:6]=[C:7]([N:11]2[CH:22]=[C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH:14]=[N:12]2)[CH:8]=[CH:9][CH:10]=1
Reactant: NNc1cccc(OC(F)F)c1
Reactant: CCOC(=O)C(C=O)C=O
Agent: Cl
Solvent: CCO
Solvent: CCCCC
Product: CCOC(=O)c1cnn(-c2cccc(OC(F)F)c2)c1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
(3-(Difluoromethoxy)phenyl)hydrazine hydrochloride (4.2 g, 19.9 mmol; CAS 479581-64-1) was suspended in ethanol (80 ml) and cooled to 0° C. A solution of ethyl 2-formyl-3-oxopropanoate (2.87 g, 19.9 mmol; CAS 80370-42-9) in ethanol (40 ml) was added, and the reaction was stirred overnight. The solvent was removed under reduced pressure and the residue partitioned between sodium bicarbonate solution and ethyl acetate. The organic layers were combined, dried (MgSO4) and evaporated to yield an orange solid. The solid was suspended in pentane (50 ml) and stirred at 35° C. for 90 min. The suspension was cooled in an ice bath for one hour and the solid was filtered and washed with pentane. After drying 5.12 g (91%) of a yellow solid was obtained MS (ISP): 283.1 ([M+H]+).
Reaction SMILES: [C:1]([C:3]1[CH:42]=[CH:41][C:6]([CH2:7][N:8]2[CH2:13][CH2:12][N:11]([C:14]3[S:15][C:16]([C:19]([NH:21][C:22]4[CH:27]=[C:26]([C:28]5[S:29][CH:30]=[CH:31][CH:32]=5)[CH:25]=[CH:24][C:23]=4[NH:33]C(=O)OC(C)(C)C)=[O:20])=[CH:17][N:18]=3)[CH2:10][CH2:9]2)=[CH:5][CH:4]=1)#[N:2].C(Cl)Cl.C(O)(C(F)(F)F)=O>>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[CH2:13][CH2:12][N:11]([C:14]3[S:15][C:16]([C:19]([NH:21][C:22]4[CH:27]=[C:26]([C:28]5[S:29][CH:30]=[CH:31][CH:32]=5)[CH:25]=[CH:24][C:23]=4[NH2:33])=[O:20])=[CH:17][N:18]=3)[CH2:10][CH2:9]2)=[CH:41][CH:42]=1)#[N:2]
Reactant: CC(C)(C)OC(=O)Nc1ccc(-c2cccs2)cc1NC(=O)c1cnc(N2CCN(Cc3ccc(C#N)cc3)CC2)s1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: N#Cc1ccc(CN2CCN(c3ncc(C(=O)Nc4cc(-c5cccs5)ccc4N)s3)CC2)cc1
Yield: 58.7 %

Procedure:
A solution of compound 340 (96 mg, 0.16 mmol) in 1:1 DCM/TFA (6 mL) was stirred at room temperature for 1 hour. The mixture was concentrated and purified by flash chromatography using EtOAc as an eluent, to afford the title compound 341 (47 mg, 59% yield). 1H NMR: (400.2 MHz, CD3OD) δ (ppm): 7.95 (br.s, 1H), 7.75 (m, 1H), 7.68 (m, 2H), 7.53 (t, 1H, J=7.6 Hz), 7.42 (s, 1H), 7.33 (d, 1H, J=8.2 Hz), 7.20 (m, 2H), 7.00 (m, 1H), 6.87 (d, 1H, J=8.3 Hz), 3.72 (s, 2H), 3.60 (m, 4H), 2.68 (m, 4H). MS: calc: 500.1; found: 501.2 (M+H)
Reaction SMILES: C(N(CC)CC)C.[CH3:8][S:9](Cl)(=[O:11])=[O:10].[Cl:13][C:14]1[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=1[C@@:21]([OH:32])([CH2:26][N:27]1[CH:31]=[N:30][CH:29]=[N:28]1)[C@@H:22]([CH3:25])[CH2:23][OH:24].C(=O)([O-])O.[Na+]>C(Cl)Cl>[Cl:13][C:14]1[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=1[C@:21]([OH:32])([C@@H:22]([CH3:25])[CH2:23][O:24][S:9]([CH3:8])(=[O:11])=[O:10])[CH2:26][N:27]1[CH:31]=[N:30][CH:29]=[N:28]1
Reactant: CS(=O)(=O)Cl
Reactant: C[C@@H](CO)[C@](O)(Cn1cncn1)c1ccc(Cl)cc1Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: C[C@@H](COS(C)(=O)=O)[C@](O)(Cn1cncn1)c1ccc(Cl)cc1Cl
Yield: 101 %

Procedure:
61 mg (0.61 mmole) of triethylamine and 64 mg (0.56 mmole) of methanesulfonyl chloride were added at 0° C., whilst stirring, to a solution of 74 mg (0.231 mmole) of (2S*,3R*)-3-(2,4-dichlorophenyl)-2-methyl-4-(1H-1,2,4-triazol-1-yl)-1,3-butanediol in 2 ml of methylene chloride. Fifteen minutes later the reaction mixture was mixed with a dilute aqueous solution of sodium hydrogencarbonate and extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride, and the solvent was removed by evaporation under reduced pressure, to give 92 mg of a crude product.
Reaction SMILES: C([Li])CCC.C(N[CH:10]([CH3:12])[CH3:11])(C)C.[I:13][C:14]1C(C)=[C:16]([CH:20]=[CH:21][CH:22]=1)[C:17]([OH:19])=[O:18].IC.Cl>O1CCCC1>[I:13][C:14]1[C:12]([CH2:10][CH3:11])=[C:16]([CH:20]=[CH:21][CH:22]=1)[C:17]([OH:19])=[O:18]
Reactant: Cc1c(I)cccc1C(=O)O
Reactant: CC(C)NC(C)C
Agent: Cl
Agent: [Li]CCCC
Solvent: CI
Solvent: C1CCOC1
Product: CCc1c(I)cccc1C(=O)O
Temperature: -50 °C
Reaction time: 0.5 h
Yield: 103.9 %

Procedure:
A n-butyllithium-1.58M n-hexane solution (36.2 ml, 57.2 mmol) was added dropwise to a solution of diisopropylamine (8.02 ml, 57.2 mmol) in tetrahydrofuran (114 ml) under ice-cooling, and the mixture was further stirred for 30 minutes. After the reaction mixture was cooled to −50° C., a solution of 3-iodo-2-methylbenzoic acid (5.00 g, 19.1 mmol) in tetrahydrofuran (38 ml) was added thereto. After the mixture was stirred for 1 hour, iodomethane (9.51 ml, 153 mmol) was added thereto and the temperature of the mixture was raised from −50° C. to −20° C. over 1 hour. The reaction mixture was poured into 1N hydrochloric acid and extracted with ethyl acetate. The organic layer was successively washed with 1N hydrochloric acid, water and a saturated aqueous NaCl solution and dried with anhydrous sodium sulfate. The solvent was removed under reduced pressure to give 3-iodo-2-ethylbenzoic acid (5.48 g, yield: 100%).
Reaction SMILES: [CH:1]1([N:7]2[C:11](=[O:12])[C:10]([NH:13][C:14]([C:16]3[C:20]([CH3:21])=[C:19]([CH:22]=[O:23])[O:18][N:17]=3)=[O:15])=[C:9]([CH3:24])[N:8]2[CH3:25])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:26]([Mg]Br)[CH:27]=[CH2:28].CCOCC.[NH4+].[Cl-]>C1COCC1>[CH:1]1([N:7]2[C:11](=[O:12])[C:10]([NH:13][C:14]([C:16]3[C:20]([CH3:21])=[C:19]([CH:22]([OH:23])[CH2:28][CH:27]=[CH2:26])[O:18][N:17]=3)=[O:15])=[C:9]([CH3:24])[N:8]2[CH3:25])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: Cc1c(C(=O)Nc2c(C)n(C)n(C3CCCCC3)c2=O)noc1C=O
Reactant: C=CC[Mg]Br
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CCOCC
Product: C=CCC(O)c1onc(C(=O)Nc2c(C)n(C)n(C3CCCCC3)c2=O)c1C
Temperature: 25 °C

Procedure:
A solution of N-(2-cyclohexyl-1,5-dimethyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-5-formyl-4-methylisoxazole-3-carboxamide (53 mg, 0.153 mmol) in THF (1.5 mL) was cooled to 0° C. and 1M allylmagnesium bromide in Et2O (337 μl, 0.337 mmol) was added dropwise over 15 mins. The reaction mixture was warmed to room temperature and saturated NH4Cl (aq) was added. The aqueous layer was extracted with DCM (×3). The combined organic extracts were passed through a phase separating cartridge and the organic solvent was removed under reduced pressure. The crude material was adsorbed onto silica and purification by chromatography eluting with 50-100% EtOAc in iso-hexane afforded the title compound.
Reaction SMILES: [CH2:1]([I:12])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH:10]=[CH2:11].[I-].[Na+].[CH2:15]([N:17]([CH2:20][CH3:21])[CH2:18][CH3:19])[CH3:16]>CC(C)=O.C(C(C)=O)C>[I-:12].[CH2:1]([N+:17]([CH2:20][CH3:21])([CH2:18][CH3:19])[CH2:15][CH3:16])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH:10]=[CH2:11].[CH2:1]([I:12])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH:10]=[CH2:11]
Reactant: CCN(CC)CC
Agent: C=CCCCCCCCCCI
Agent: [I-]
Agent: [Na+]
Solvent: CCC(C)=O
Solvent: CC(C)=O
Product: C=CCCCCCCCCC[N+](CC)(CC)CC

Procedure:
Polyalkylenes, which are available, can be prepared by polymerization of olefins, especially the 1-olefins such as 1-butene, 1-pentene, undecylenic acid-trimethylsilyl ester, and the like, using an isotactic catalyst, especially TiCl3AA/diethylaluminum chloride in toluene. Undecylenic acid-trimethylsilyl ester was, for example, prepared from the reaction of undecylenic acid with trimethylsilyl chloride; undecylenyl iodide was prepared from undecylenol; and undecylenol was allowed to react with thionyl chloride and pyridine to form undecylenyl chloride which was then converted to undecylenyl iodide by reaction with sodium iodide in acetone or methyl ethyl ketone. Undecylenyl triethylammonium iodide was formed by the reaction of undecylenyl iodide and triethylamine in alcohol.