Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C@@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH2:7][CH2:8][C:9]1[O:10][C:11]2[CH:17]=[CH:16][C:15]([C:18]3[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][CH:19]=3)=[CH:14][C:12]=2[CH:13]=1.[O-:26][Mn](=O)(=O)=O.[K+].[O-]S([O-])(=O)=O.[Mg+2]>CC(C)=O.O>[CH3:1][C@@H:2]1[CH2:6][CH2:5][C:4](=[O:26])[N:3]1[CH2:7][CH2:8][C:9]1[O:10][C:11]2[CH:17]=[CH:16][C:15]([C:18]3[CH:19]=[CH:20][C:21]([C:22]#[N:23])=[CH:24][CH:25]=3)=[CH:14][C:12]=2[CH:13]=1
Reactant: O=[Mn](=O)(=O)[O-]
Reactant: C[C@@H]1CCCN1CCc1cc2cc(-c3ccc(C#N)cc3)ccc2o1
Agent: O=S(=O)([O-])[O-]
Agent: [K+]
Agent: [Mg+2]
Solvent: O
Solvent: CC(C)=O
Product: C[C@@H]1CCC(=O)N1CCc1cc2cc(-c3ccc(C#N)cc3)ccc2o1
Yield: 2 %

Procedure:
The mono-(L)-tartaric acid salt of the product of Example 1D (96 mg, 0.20 mmol) was suspended in acetone (10 mL) and treated with a solution of KMnO4 (158 mg, 1.0 mmol) and MgSO4 (120 mg, 1.0 mmol) in water (5 mL) over 30 minutes. After the purple color had disappeared, the solids were filtered off. The filtrate was diluted with EtOAc, washed with aqueous potassium dihydrogen phosphate, concentrated, and purified by HPLC [Waters Nova-Pak HR C18 column (25 mm×100 mm, 6 μm particle size) using a gradient of 10% to 100% MeCN/0.1% aqueous TFA over 8 min (10 min run time) at a flow rate of 40 mL/min.] to provide the title compound (2% yield). MS (ESI APCI) m/z 345 (M+H)+; 1HNMR (300 MHz, CD3OD) δ 1.22 (d, 3 H), 1.55-1.64 (m, 1 H), 2.15-2.32 (m, 2 H), 2.34-2.42 (m, 1 H), 2.99-3.13 (m, 2 H), 3.39-3.46 (m, 1 H), 3.68-3.76 (m, 1 H), 3.89-3.97 (m, 1 H), 6.65 (s, 1 H), 7.51-7.56 (m, 2 H), 7.76-7.84 (m, 5 H).
Reaction SMILES: C1(=O)[O:6][C:4](=[O:5])[CH:3]=[CH:2]1.[OH-].[Na+].[C:10]([OH:14])(=[O:13])[CH:11]=[CH2:12].OO.S(OOS([O-])(=O)=O)([O-])(=O)=O.[Na+].[Na+]>O>[C:4]([OH:6])(=[O:5])[CH:3]=[CH2:2].[C:4]([OH:6])(=[O:5])/[CH:12]=[CH:11]\[C:10]([OH:14])=[O:13]
Reactant: O=C1C=CC(=O)O1
Agent: C=CC(=O)O
Agent: O=S(=O)([O-])OOS(=O)(=O)[O-]
Agent: OO
Solvent: O
Product: O=C(O)/C=C\C(=O)O
Reaction time: 0.83 h

Procedure:
First of all, 310 g of ion-exchanged water and 400 g of maleic anhydride (473.7 g as maleic acid) were charged into a SUS-made separable flask of 5 liters in capacity as fitted with a reflux condenser, a stirrer, and a thermometer. Thereto, 708.3 g of 48 wt % aqueous sodium hydroxide solution (hereinafter referred to as 48%NaOHaq) was gradually added under stirring, so that the initial neutralization degree was 85 mol %, and that the initial solid component concentration was 50.9 wt %. Thereafter, while being stirred, the aqueous solution in the flask was heated to its boiling point under normal pressure. Next, under stirring, 450 g of 80 wt % aqueous acrylic acid solution (hereinafter referred to as 80%AAaq), 114.3 g of 35 wt % aqueous hydrogen peroxide solution (hereinafter referred to as 35%H2O2aq), 166.7 g of 15 wt % aqueous sodium persulfate solution (hereinafter referred to as 15%NaPSaq), and 33.3 g of ion-exchanged water were dropped from different nozzles respectively as follows: 80%AAaq was dropped over a period of 120 minutes; 35%H2O2aq was dropped over a period of 50 minutes starting at the same time with the dropping of 80%AAaq; 15%NaPSaq and ion-exchanged water were dropped over a period of 80 minutes since the dropping end of 35%H2O2aq, namely, starting 50 minutes later than the dropping start of 80%AAaq, and ending 10 minutes later than the dropping end of 80%AAaq. After the dropping end of all components, the reaction solution was kept in a boiling point reflux state for another 20 minutes to complete the polymerization, thus obtaining an acrylic acid-maleic acid copolymer (salt) having a neutralization degree of 64.5 mol % and a solid component concentration of 50 wt % at the end of the polymerization. Thereafter, the pH of this acrylic acid-maleic acid copolymer (salt) was adjusted to 8 with a 48 wt % aqueous NaOH solution.
Reaction SMILES: [Cl:1][C:2]1[C:3]([F:26])=[CH:4][C:5]([N+:23]([O-])=O)=[C:6]([S:8]([NH:11][C:12]2[CH:13]=[CH:14][C:15]([Cl:22])=[C:16]3[C:21]=2[N:20]=[CH:19][CH:18]=[CH:17]3)(=[O:10])=[O:9])[CH:7]=1.Cl[Sn]Cl>Cl.CCO>[NH2:23][C:5]1[CH:4]=[C:3]([F:26])[C:2]([Cl:1])=[CH:7][C:6]=1[S:8]([NH:11][C:12]1[CH:13]=[CH:14][C:15]([Cl:22])=[C:16]2[C:21]=1[N:20]=[CH:19][CH:18]=[CH:17]2)(=[O:9])=[O:10]
Reactant: O=[N+]([O-])c1cc(F)c(Cl)cc1S(=O)(=O)Nc1ccc(Cl)c2cccnc12
Agent: Cl
Agent: Cl[Sn]Cl
Solvent: CCO
Product: Nc1cc(F)c(Cl)cc1S(=O)(=O)Nc1ccc(Cl)c2cccnc12
Yield: 7.8 %

Procedure:
In a similar fashion using route 1 general procedure 4, 5-chloro-N-(5-chloro-quinolin-8-yl)-4-fluoro-2-nitro-benzenesulfonamide (Intermediate 285) (210 mg, 5.0 mmol), SnCl2 (382 mg, 2.0 mmol), 6N HCl (4 drops) and EtOH (5 ml) for 30 h at 90° C. gave the title compound (150 mg, 77%) after purification by column chromatography with DCM as the eluent.
Reaction SMILES: NC(N)=S.ClCC([N:9]1[CH2:18][CH2:17][C:16]2[C:11](=[CH:12][C:13]([O:21][CH3:22])=[C:14]([O:19][CH3:20])[CH:15]=2)[CH:10]1[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=O>CCO>[O:19]([C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][C:13]=1[O:21][CH3:22])[CH:10]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[NH:9][CH2:18][CH2:17]2)[CH3:20]
Reactant: COc1cc2c(cc1OC)C(c1ccccc1)N(C(=O)CCl)CC2
Agent: NC(N)=S
Solvent: CCO
Product: COc1cc2c(cc1OC)C(c1ccccc1)NCC2

Procedure:
Heat a mixture of thiourea (45 mg), the product of step B and etanol (8 mL) at reflux for 3 h. Remove the solvent in vacuo, dissolve the residue in chloroform and filter. Concentrate the filtrate to give 153 mg of the title compound. 1H NMR (CDCl3); δ 7.4-7.18 (5 H, m); 6.63 (1 H, s); 6.24 (1 H, s); 5.03 (1 H, s); 3.85 (3 H, s); 3.61 (3 H, s); 3.28-2.65 (4 H, m); 2.3 (1 H, br. s).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([C:8](=[O:10])[CH3:9])[CH:5]=[CH:6][CH:7]=1.[CH:11]1([Mg]Cl)[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1>C(OCC)C>[CH:11]1([C:8]([C:4]2[CH:3]=[C:2]([OH:1])[CH:7]=[CH:6][CH:5]=2)([OH:10])[CH3:9])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1
Reactant: Cl[Mg]C1CCCCC1
Reactant: CC(=O)c1cccc(O)c1
Solvent: CCOCC
Product: CC(O)(c1cccc(O)c1)C1CCCCC1

Procedure:
By using 3′-hydroxyacetophenone (200 mg) and a 2 M solution of cyclohexylmagnesium chloride in diethyl ether (2.2 ml) as starting materials, the title compound (69.6 mg) was obtained in the same manner as that of Reference Example 69.
Reaction SMILES: C[O:2][C:3]1[CH:4]=[C:5]2[C:13](=[CH:14][CH:15]=1)[N:12]([CH3:16])[C:11]1[C:6]2=[CH:7][CH:8]=[C:9]2[N:19]([CH3:20])[N:18]=[CH:17][C:10]2=1.[Al+3].[Cl-].[Cl-].[Cl-].CCS.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH3:20][N:19]1[C:9]2=[CH:8][CH:7]=[C:6]3[C:11]([N:12]([CH3:16])[C:13]4[C:5]3=[CH:4][C:3]([OH:2])=[CH:15][CH:14]=4)=[C:10]2[CH:17]=[N:18]1
Reactant: COc1ccc2c(c1)c1ccc3c(cnn3C)c1n2C
Agent: O=C([O-])O
Agent: [Al+3]
Agent: [Cl-]
Solvent: CCS
Solvent: ClCCl
Product: Cn1ncc2c1ccc1c3cc(O)ccc3n(C)c12
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A mixture of 7-methoxy-3,10-dimethyl-3,10-dihydro-2,3,10-triaza-cyclopenta[a]fluorene (55 mg, 0.21 mmol), AlCl3 (0.84 mmol, 4.0 eq.) and EtSH (0.63 mmol, 3.0 eq.) in CH2Cl2 (2 mL) was stirred at room temperature for 16 hours. The reaction mixture was poured into cold saturated NaHCO3 solution, extracted with CH2Cl2, washed with brine and dried, concentrated to yield the crude product. The crude product was then purified by chromatography to yield the title compound as a white solid.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:14]([NH2:15])[C:13]([CH2:16][CH2:17][CH3:18])=[N:12][C:7]=3[CH:8]=[N:9][C:10]=2[CH:11]=1.CO[C:21](OC)([CH3:23])[CH3:22]>C(#N)C.C(O)(=O)C.C(Cl)(Cl)Cl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:14]([N:15]=[C:21]([CH3:23])[CH3:22])[C:13]([CH2:16][CH2:17][CH3:18])=[N:12][C:7]=3[CH:8]=[N:9][C:10]=2[CH:11]=1
Reactant: CCCc1nc2cnc3cc(Br)ccc3c2n1N
Reactant: COC(C)(C)OC
Solvent: CC(=O)O
Solvent: CC#N
Solvent: ClC(Cl)Cl
Product: CCCc1nc2cnc3cc(Br)ccc3c2n1N=C(C)C
Temperature: 100 °C
Reaction time: 16 h
Yield: 92.4 %

Procedure:
A suspension of 7-bromo-2-propyl-1H-imidazo[4,5-c]quinolin-1-amine (17.6 g, 57.7 mmol) in 160 mL of acetonitrile and 40 mL of glacial acetic acid was treated with 2,2-dimethoxypropane (35.5 mL, 288 mmol). The reaction mixture was heated to 100° C. under an atmosphere of nitrogen. After 16 h, the reaction was cooled to ambient temperature and concentrated under reduced pressure to yield a brown oil. The oil was dissolved in CHCl3 (200 mL). The CHCl3 solution was washed with saturated NaHCO3 solution (2×50 mL), water (50 mL) and brine (50 mL). The organic portion was then dried over Na2SO4, filtered and concentrated under reduced pressure to yield 18.4 g of N-(7-bromo-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)isopropylideneamine as a red/brown foam.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([OH:11])[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9].[O:12]1[CH:17]=[CH:16][CH2:15][CH2:14][CH2:13]1.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>ClCCl>[O:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH:13]1[O:11][C:4]1[CH:5]=[CH:6][C:7]([N+:8]([O-:10])=[O:9])=[C:2]([F:1])[CH:3]=1
Reactant: C1=COCCC1
Reactant: O=[N+]([O-])c1ccc(O)cc1F
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: O=[N+]([O-])c1ccc(OC2CCCCO2)cc1F
Reaction time: 8 h

Procedure:
To the mixture of 3-fluoro-4-nitrophenol (25 g, 0.160 mol) and 3,4-dihydro-2H-pyran (14 g, 0.167 mol)in dicloromethane (200 ml), pyridinium p-toluenesulfonate (4.0 g, 16 mol) was added portionly under ice-water bath. After overnight at room temperature, the reaction mixture was pored to Si-column chromatography. Eluting by Hexane Ethyl acetate (3:1), the desired product was obtained at 35.5 g (92%) as light yellow solid.
Reaction SMILES: Cl.[C:2]([C:4]1[CH:5]=[C:6]([N:10]2[CH2:15][C@@H:14]3[CH2:16][C@H:11]2[CH2:12][N:13]3[C:17]2[CH:29]=[CH:28][C:20]([C:21]([O:23]C(C)(C)C)=[O:22])=[CH:19][CH:18]=2)[CH:7]=[CH:8][CH:9]=1)#[N:3]>[N+](C)([O-])=O>[C:2]([C:4]1[CH:5]=[C:6]([N:10]2[CH2:15][C@@H:14]3[CH2:16][C@H:11]2[CH2:12][N:13]3[C:17]2[CH:29]=[CH:28][C:20]([C:21]([OH:23])=[O:22])=[CH:19][CH:18]=2)[CH:7]=[CH:8][CH:9]=1)#[N:3]
Reactant: CC(C)(C)OC(=O)c1ccc(N2C[C@@H]3C[C@H]2CN3c2cccc(C#N)c2)cc1
Agent: Cl
Solvent: C[N+](=O)[O-]
Product: N#Cc1cccc(N2C[C@@H]3C[C@H]2CN3c2ccc(C(=O)O)cc2)c1
Reaction time: 2 h
Yield: 43.6 %

Procedure:
To a saturated mixture of HCl (gas) and nitromethane (25 mL) was added title compound 247 (0.85 g, 2.264 mmol). The clear solution was stirred 2 h then concentrated. The beige residue was triturated with ether overnight and filtered to afford title compound 248 (315 mg, 39%) as a beige solid. LRMS (ESI): (calc.) 319.13 (found) 320.3 (MH)+.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:11](=O)[CH2:12][C:13](=O)[C:14]([F:17])([F:16])[F:15])[CH:5]=[C:6]([F:10])[C:7]=1[S:8][CH3:9].Cl.[F:21][C:22]1[CH:27]=[CH:26][C:25]([NH:28][NH2:29])=[CH:24][CH:23]=1>C(O)C.Cl>[F:1][C:2]1[CH:3]=[C:4]([C:11]2[N:28]([C:25]3[CH:26]=[CH:27][C:22]([F:21])=[CH:23][CH:24]=3)[N:29]=[C:13]([C:14]([F:17])([F:16])[F:15])[CH:12]=2)[CH:5]=[C:6]([F:10])[C:7]=1[S:8][CH3:9]
Reactant: CSc1c(F)cc(C(=O)CC(=O)C(F)(F)F)cc1F
Reactant: NNc1ccc(F)cc1
Agent: Cl
Solvent: CCO
Product: CSc1c(F)cc(-c2cc(C(F)(F)F)nn2-c2ccc(F)cc2)cc1F
Temperature: 25 °C
Reaction time: 72 h

Procedure:
1-[3,5-difluoro-4-(methylthio)phenyl]-4,4,4-trifluoro-butane-1,3-dione (1.09 g, 3.6 mmol) dissolved in ethanol (150 mL). One drop of concentrated hydrochloric acid was added and 4-fluorophenylhydrazine hydrochloride (0.69 g, 4.0 mmol). The reaction was stirred at ambient temperature for 72 hours. Solvent was removed in vacuo and the residue was dissolved in ethyl acetate (100 mL) extracted with water (2×100 mL), saturated ammonium chloride (2×150 mL) and dried over sodium sulfate. The solvent was removed in vacuo and the 5-[3,5-difluoro-4-(methylthio)-phenyl]-1-(4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazole was obtained by crystallization from ethyl acetate and hexanes (0.71 g, 50%). 1H NMR (CDCl3/300 MHz) 7.36-7.29 (m, 2H), 7.18-7.13 (m, 2H), 6.81-6.77 (m, 3H), 2.53 (s, 3H). ESHRMS m/z 389.0557 (M+H+, Calcd 389.0547). Anal. Calcd for C17H10F6N2S: C, 52.58; H, 2.34; N, 7.21; Found: C, 52.45; H, 2.34; N, 7.15.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([N:10]3[CH2:15][CH2:14][O:13][CH2:12][CH2:11]3)[CH:8]=2)[CH:3]=[CH:2]1.[CH3:16][C:17]1[C:22](/[CH:23]=[CH:24]/[N+:25]([O-:27])=[O:26])=[CH:21][CH:20]=[CH:19][C:18]=1[NH:28][C:29](=[O:38])[O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>C1COCC1>[CH3:16][C:17]1[C:22]([CH:23]([C:3]2[C:4]3[C:9](=[CH:8][C:7]([N:10]4[CH2:15][CH2:14][O:13][CH2:12][CH2:11]4)=[CH:6][CH:5]=3)[NH:1][CH:2]=2)[CH2:24][N+:25]([O-:27])=[O:26])=[CH:21][CH:20]=[CH:19][C:18]=1[NH:28][C:29](=[O:38])[O:30][CH2:31][C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1
Reactant: Cc1c(/C=C/[N+](=O)[O-])cccc1NC(=O)OCc1ccccc1
Reactant: c1cc2ccc(N3CCOCC3)cc2[nH]1
Solvent: C1CCOC1
Product: Cc1c(NC(=O)OCc2ccccc2)cccc1C(C[N+](=O)[O-])c1c[nH]c2cc(N3CCOCC3)ccc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 33.7 %

Procedure:
A solution of 4-(1H-indol-6-yl)morpholine (1.1132 g, 5.50 mmol) and (E)-benzyl 2-methyl-3-(2-nitrovinyl)phenylcarbamate (2.58 g, 8.26 mmol) in THF (50 mL) was concentrated in vacuo. The residue was melted at 137° C. and stirred overnight. After cooling to room temperature, the crude product was purified by flash chromatography using an ISCO 330 g column (solid loading) eluting with 40-80% EtOAc/hexanes to give the desired product (0.9544 g, 1.855 mmol, 33.7% yield) as a light brown solid.
Reaction SMILES: [NH2:1][C:2]1[CH:27]=[CH:26][C:5]([O:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:21][CH2:22][CH2:23][O:24][CH3:25])=[C:14]([C:17]([O:19][CH3:20])=[O:18])[CH:15]=3)[N:10]=[CH:9][CH:8]=2)=[CH:4][C:3]=1[Cl:28].N1C=CC=CC=1.O1CCCC1.Cl[C:41]([O:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)=[O:42]>O>[Cl:28][C:3]1[CH:4]=[C:5]([CH:26]=[CH:27][C:2]=1[NH:1][C:41]([O:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)=[O:42])[O:6][C:7]1[C:16]2[C:11](=[CH:12][C:13]([O:21][CH2:22][CH2:23][O:24][CH3:25])=[C:14]([C:17]([O:19][CH3:20])=[O:18])[CH:15]=2)[N:10]=[CH:9][CH:8]=1
Reactant: O=C(Cl)Oc1ccccc1
Reactant: COCCOc1cc2nccc(Oc3ccc(N)c(Cl)c3)c2cc1C(=O)OC
Solvent: C1CCOC1
Solvent: c1ccncc1
Solvent: O
Product: COCCOc1cc2nccc(Oc3ccc(NC(=O)Oc4ccccc4)c(Cl)c3)c2cc1C(=O)OC
Reaction time: 0.67 h

Procedure:
Methyl 4-(4-amino-3-chlorophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxylate (3.2 g), pyridine (0.71 ml) and tetrahydrofuran (50 ml) were stirred while cooling on ice, and then 1.1 ml of phenyl chloroformate was added dropwise. After 40 minutes, 0.8 ml of pyridine and 1.1 ml of phenyl chloroformate were added and the mixture was stirred for an additional 10 minutes. Water was added, extraction was performed with ethyl acetate, and the extract solution was passed through a glass filter coated with silica gel. The silica gel was washed with ethyl acetate, the solvent was distilled off under reduced pressure, hexane and ethyl acetate were added to the residue and the solid was filtered out to obtain 3.2 g of a faint red solid.
Reaction SMILES: [OH-].[K+].C(O)C.[Cl:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([Cl:13])[C:8]=1[OH:14].[Cl:15][C:16]1[N:21]=[C:20](Cl)[CH:19]=[C:18]([Cl:23])[N:17]=1>O1CCCC1>[Cl:15][C:16]1[N:17]=[C:18]([Cl:23])[C:19]([O:14][C:8]2[C:7]([Cl:6])=[CH:12][CH:11]=[CH:10][C:9]=2[Cl:13])=[CH:20][N:21]=1
Reactant: Clc1cc(Cl)nc(Cl)n1
Reactant: Oc1c(Cl)cccc1Cl
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: C1CCOC1
Product: Clc1ncc(Oc2c(Cl)cccc2Cl)c(Cl)n1
Yield: 55.1 %

Procedure:
Potassium hydroxide/ethanol (10%; 0.035 mol) was added to a solution of 2,6-dichlorophenol (0.035 mol) in tetrahydrofuran (100 ml). The mixture was stirred and 2,4,6-trichloropyrimidine (0.044 mol) was added. The mixture was stirred overnight at 60° C. The reaction was quenched with NaOH 1N solution. The aqueous layers were extracted with EtOAc several times and then the organic layers were combined and washed with NaOH 3N and saturated NaCl, dried and concentrated. The residue was recrystallized from CH2Cl2/hexane. The precipitate was filtered off and dried, yielding 5.98 g 2,4-dichloro-(2,6-dichlorophenoxy)pyrimidine (55%) (interm. 12).
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].C(=O)([O-])[O-].[K+].[K+].Cl.[BH4-].[Na+].[C:19](O)(=O)[CH2:20][C:21](CC(O)=O)(C(O)=O)O>CN(C)C=O.BrC(C)C.CO>[CH:20]([O:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4][OH:5])([CH3:21])[CH3:19]
Reactant: O=Cc1ccccc1O
Reactant: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [BH4-]
Solvent: CC(C)Br
Solvent: CN(C)C=O
Solvent: CO
Product: CC(C)Oc1ccccc1CO
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 2-hydroxybenzaldehyde (0.5 ml) in dimethylformamide (5 ml), 1.35 ml of 2-bromopropane and 1.98 g of potassium carbonate were added, and the reaction solution was stirred overnight at room temperature. To the reaction solution was added 1N hydrochloric acid, and the mixture was extracted with ethyl acetate. The combined organic layers were washed with a saturated saline solution and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to afford a crude product as a yellow oil. To a solution of the crude product in methanol (5 ml), 362 mg of sodium borohydride was added under ice-cooling, and the reaction solution was stirred at room temperature for 30 minutes. To the reaction solution was added 10% aqueous citric acid, and the mixture was extracted with ethyl acetate. The combined organic layers were washed with a saturated saline solution and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue obtained was purified by silica gel column chromatography (eluent: hexane/ethyl acetate (98:2-50:50)) to afford the title compound as a colorless oil.
Reaction SMILES: [C:1]12([CH2:11]O)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.C12(CBr)CC3CC(CC(C3)C1)C2.Br.[ClH:26]>[Br-].[Zn+2].[Br-].[Cl-].[Zn+2].[Cl-]>[C:1]12([CH2:11][Cl:26])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2
Reactant: OCC12CC3CC(CC(C3)C1)C2
Reactant: Cl
Agent: Br
Agent: BrCC12CC3CC(CC(C3)C1)C2
Agent: [Br-]
Product: ClCC12CC3CC(CC(C3)C1)C2
Yield: 91 %

Procedure:
Chlorination reaction of 1-adamantyl methylalcohol which was obtained by the same method described in (1) was carried out under the same conditions for the bromination reaction shown in (2) except that zinc bromide and hydrobromic acid were replaced by zinc chloride and hydrochloric acid respectively. The product was purified by recrystallized from methanol. Melting point of 1-adamantyl methyl chloride thus obtained was 32°-34° C and the yield was 91%.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.[F-].[Cs+].BrC1C=CC(OC[CH2:21][NH:22][CH2:23][C@@H:24]([C:26]2[CH:27]=[CH:28][C:29]([O:46][CH2:47][O:48][CH2:49][CH2:50][Si:51]([CH3:54])([CH3:53])[CH3:52])=[C:30]([N:32](OCOCC[Si](C)(C)C)[S:33]([CH3:36])(=[O:35])=[O:34])[CH:31]=2)[OH:25])=CC=1>C(O)C.O1CCOCC1.O1CCCC1.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>[OH:25][C@H:24]([C:26]1[CH:27]=[CH:28][C:29]([O:46][CH2:47][O:48][CH2:49][CH2:50][Si:51]([CH3:52])([CH3:53])[CH3:54])=[C:30]([N:32]([CH2:47][O:48][CH2:49][CH2:50][Si:51]([CH3:54])([CH3:53])[CH3:52])[S:33]([CH3:36])(=[O:34])=[O:35])[CH:31]=1)[CH2:23][NH:22][CH2:21][CH2:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)=[CH:5][CH:4]=1
Reactant: COc1ccc(B(O)O)cc1
Reactant: C[Si](C)(C)CCOCOc1ccc([C@@H](O)CNCCOc2ccc(Br)cc2)cc1N(OCOCC[Si](C)(C)C)S(C)(=O)=O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cs+]
Agent: [F-]
Solvent: C1CCOC1
Solvent: C1COCCO1
Solvent: CCO
Product: COc1ccc(-c2ccc(OCCNC[C@H](O)c3ccc(OCOCC[Si](C)(C)C)c(N(COCC[Si](C)(C)C)S(C)(=O)=O)c3)cc2)cc1
Temperature: 100 °C
Reaction time: 12 h

Procedure:
A solution of 4-methoxyphenylboronic acid (0.013 g) in ethanol (0.06 mL), an aqueous solution (0.10 mL) of cesium fluoride (0.019 g) and a solution of tetrakis(triphenylphosphine)palladium (0.003 g) in 1,4-dioxane (0.10 mL) were added successively to a solution of N-[5-{(R)-2-[2-(4-bromophenoxy)-ethylamino]-1-hydroxyethyl}-2-(2-trimethylsilylethoxymethoxy)phenyl]-N-(2-trimethylsilylethoxymethoxy)methanesulfonamide (0.03 g) in 1,4-dioxane (0.20 mL), and the mixture was stirred at 100° C. for 12 hrs. After being cooled to room temperature, the reaction mixture was diluted with tetrahydrofuran, and purified by SCX ion exchange column chromatography (Varian Bond Elut 500 mg, preconditioning: tetrahydrofuran, washing solvent: tetrahydrofuran, eluent: 2 mol/L ammonia in methanol). The solvent was evaporated under reduced pressure to afford N-[5-{(R)-1-hydroxy-2-[2-(4′-methoxybiphenyl-4-yloxy)ethylamino]ethyl}-2-(2-trimethylsilylethoxymethoxy)phenyl]-N-(2-trimethylsilylethoxymethyl)methanesulfonamide.
Reaction SMILES: [C:1]([O-:4])([O-:3])=[O:2].[K+].[K+].O[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH:14][C:15](=[O:19])[C:16]([CH3:18])=[CH2:17]>O1CCCC1>[C:16]([O:2][C:1]([O:4][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH:14][C:15](=[O:19])[C:16]([CH3:18])=[CH2:17])=[O:3])([CH3:18])([CH3:17])[CH3:15]
Reactant: O=C([O-])[O-]
Reactant: C=C(C)C(=O)Nc1ccccc1O
Agent: [K+]
Solvent: C1CCOC1
Product: C=C(C)C(=O)Nc1ccccc1OC(=O)OC(C)(C)C

Procedure:
K2CO3 (30 g) is added to a solution of 20.0 g (0.112 tool) of N-(2-hydroxyphenyl)methacrylamide in tetrahydrofuran (THF). A solution of 27 g (0.124 tool) of di-tert-butyl pyrocarbonate (di-tert-butyl dicarbonate) in THF is then added dropwise at room temperature while stirring. The reaction is complete after a few hours. The reaction mixture is poured onto ice and extracted with ethyl acetate, the organic phase is dried and the solvent is distilled off. A yellowish oil is obtained which decomposes on distillation. The product is used for polymerization without further purification.
Reaction SMILES: Br[C:2]1[CH:6]=[CH:5][N:4]([CH3:7])[N:3]=1.[CH2:8]([C:12]1[S:13][C:14]2[CH:20]=[CH:19][CH:18]=[CH:17][C:15]=2[N:16]=1)[CH2:9][C:10]#[CH:11]>>[CH3:7][N:4]1[CH:5]=[CH:6][C:2]([C:11]#[C:10][CH2:9][CH2:8][C:12]2[S:13][C:14]3[CH:20]=[CH:19][CH:18]=[CH:17][C:15]=3[N:16]=2)=[N:3]1
Reactant: C#CCCc1nc2ccccc2s1
Reactant: Cn1ccc(Br)n1
Product: Cn1ccc(C#CCCc2nc3ccccc3s2)n1
Yield: 21 %

Procedure:
The title compound was prepared in accordance with the general method of Example 108(C), from 3-bromo-1-methyl-1H-pyrazole (100 mg, 0.62 mmol) and 2-but-3-ynyl-benzo[d]thiazole (233 mg, 1.24 mmol, Example 35(A)). The crude residue was purified by flash chromatography (cyclohexane/AcOEt 7:3) to yield 35 mg (0.13 mmol, 21%) of 2-(4(1-methyl-1H-pyrazol-3-yl)but-3-ynyl)benzo[d]thiazole as a brown semi-solid.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[C:11]([I:12])=[C:10](S(C)=O)[N:9]=[C:8]([NH2:16])[N:7]=1.[C:17]1([CH2:23][CH2:24][CH2:25][NH2:26])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C1COCC1>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[N:7]=[C:8]([NH2:16])[N:9]=[C:10]([NH:26][CH2:25][CH2:24][CH2:23][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:11]=1[I:12]
Reactant: NCCCc1ccccc1
Reactant: CS(=O)c1nc(N)nc(-c2ccco2)c1I
Solvent: C1CCOC1
Product: Nc1nc(NCCCc2ccccc2)c(I)c(-c2ccco2)n1

Procedure:
From 4-furan-2-yl-5-iodo-6-methanesulfinyl-pyrimidin-2-yl-amine and 3-phenylpropylamine in THF. ES-MS m/e (%): 421 (M+H+, 100).