Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: N[C:2]1[C:10]2[C:5](=[N:6][C:7]([C:29]([CH3:32])([CH3:31])[CH3:30])=[CH:8][C:9]=2[C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18]([NH:20][C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([CH2:27][CH3:28])[CH:22]=3)=[O:19])=[CH:13][CH:12]=2)[NH:4][N:3]=1.S(=O)(=O)(O)O.N([O-])=O.[Na+]>>[C:29]([C:7]1[N:6]=[C:5]2[NH:4][N:3]=[CH:2][C:10]2=[C:9]([C:11]2[CH:12]=[CH:13][C:14]([NH:17][C:18]([NH:20][C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([CH2:27][CH3:28])[CH:22]=3)=[O:19])=[CH:15][CH:16]=2)[CH:8]=1)([CH3:32])([CH3:31])[CH3:30]
Reactant: CCc1cccc(NC(=O)Nc2ccc(-c3cc(C(C)(C)C)nc4[nH]nc(N)c34)cc2)c1
Agent: O=N[O-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Product: CCc1cccc(NC(=O)Nc2ccc(-c3cc(C(C)(C)C)nc4[nH]ncc34)cc2)c1
Yield: 42.9 %

Procedure:
In analogy to GP 6, reaction of 95.6 mg of 1-[4-(3-amino-6-tert-butyl-1H-pyrazolo-[3,4-b]pyridin-4-yl)-phenyl]-3-(3-ethyl-phenyl)-urea (0.22 mmol, 1 eq.) with 35 μL concentrated sulphuric acid and 38 mg sodium nitrite (2.5 eq.) yielded 39 mg of the desired product (42% yield).
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].CC(OCC1C2C(=CC=CC=2)C(COC(C)=O)=C2C=1C=CC=C2)=[O:9].[C:31]([NH:34][CH:35]([C:48]1[CH:52]=[CH:51][O:50][C:49]=1[Si](CC)(CC)CC)[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH3:47])(=[O:33])[CH3:32].O=O.[BH4-].[Na+]>>[C:31]([NH:34][CH:35]([C:48]1[C:49](=[O:9])[O:50][CH2:51][CH:52]=1)[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH3:47])(=[O:33])[CH3:32]
Reactant: CCCCCCCCCCCCC(NC(C)=O)c1ccoc1[Si](CC)(CC)CC
Reactant: CC(=O)OCc1c2ccccc2c(COC(C)=O)c2ccccc12
Agent: O=O
Agent: [Al+3]
Agent: [BH4-]
Product: CCCCCCCCCCCCC(NC(C)=O)C1=CCOC1=O

Procedure:
Reacting 3-(1-hydroxytridecyl)-2-triethylsilylfuran (Compound 20) with diphenylphosphoryl azide and diethyl azidocarboxylate gives 3-(1-azidotridecyl)-2-triethylsilylfuran (Compound 24). Reducing this intermediate with lithium aluminum hydride, followed by acetylation with acetic anhydide gives 3-(1-acetamido tridecyl)-2-triethylsilylfuran (Compound 25). Singlet oxygen oxidation of this amide, under conditions as in Example 1, followed by reduction with sodium borohydride gives 3-(1-acetamidotridecyl)-2(5H)-furanone (Compound 10).
Reaction SMILES: C[C:2]([C:4]1[C:9]([Cl:10])=[CH:8][C:7]([F:11])=[C:6]([F:12])[CH:5]=1)=[O:3].Cl[O-:14].[Na+].Cl>C(Cl)Cl>[Cl:10][C:9]1[CH:8]=[C:7]([F:11])[C:6]([F:12])=[CH:5][C:4]=1[C:2]([OH:3])=[O:14]
Reactant: [O-]Cl
Reactant: CC(=O)c1cc(F)c(F)cc1Cl
Agent: Cl
Agent: [Na+]
Solvent: ClCCl
Product: O=C(O)c1cc(F)c(F)cc1Cl
Yield: 85.1 %

Procedure:
To 19.1 g (0.1 mol) of 2-chloro-4,5-difluoroacetophenone, 280.4 g (0.4 mol) of a 12% sodium hypochlorite aqueous solution was added, and the mixture was reacted under reflux for 4 hours. After cooling, concentrated hydrochloric acid was dropwise added thereto until the pH became 1. The formed white crystals were dissolved in methylene chloride and separated from the aqueous phase. The separated aqueous phase was extracted twice with methylene chloride, and the extracts were added to the oil phase. Then, the solvent was distilled off to obtain 16.4 g (yield: 85.1%) of 2-chloro-4,5-difluorobenzoic acid as white crystal.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([C:11]2[C:20]3[C:15](=[CH:16][C:17]([O:24][CH2:25][CH3:26])=[C:18]([O:21][CH2:22][CH3:23])[CH:19]=3)[CH:14]=[C:13]([CH2:27][O:28]C(=O)C)[N:12]=2)[CH:7]=[CH:8][C:9]=1[Cl:10])([O-:3])=[O:2].[OH-].[Na+]>>[N+:1]([C:4]1[CH:5]=[C:6]([C:11]2[C:20]3[C:15](=[CH:16][C:17]([O:24][CH2:25][CH3:26])=[C:18]([O:21][CH2:22][CH3:23])[CH:19]=3)[CH:14]=[C:13]([CH2:27][OH:28])[N:12]=2)[CH:7]=[CH:8][C:9]=1[Cl:10])([O-:3])=[O:2]
Reactant: CCOc1cc2cc(COC(C)=O)nc(-c3ccc(Cl)c([N+](=O)[O-])c3)c2cc1OCC
Agent: [Na+]
Agent: [OH-]
Product: CCOc1cc2cc(CO)nc(-c3ccc(Cl)c([N+](=O)[O-])c3)c2cc1OCC

Procedure:
4.98 g (0.0112 M) of 1-(3-nitro-4-chlorophenyl)-3-(acetoxymethyl)-6,7-diethoxy-isoquinoline is refluxed with 50 ml of a 10% aqueous sodium hydroxide solution for 5 hours. During the hydrolysis the product is precipitated . The suspension formed is cooled, filtered, washed with water to remove sodium hydroxide, and dried. The crude product (4.27 g) is purified by treating it with 45 ml of hot, anhydrous ethanol, the suspension is cooled with ice-water, filtered, washed with 3×5 ml of anhydrous ethanol and dried. Yield 3.94 g (87.4%), m. p. 187° to 188° C.
Reaction SMILES: [CH3:1][CH:2]1[C:10]2[CH:9]=[C:8]3[O:11][CH2:12][O:13][C:7]3=[CH:6][C:5]=2[C:4](=[O:14])[N:3]1[CH2:15][CH2:16][CH:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1.O1CCC[CH2:31]1.C([N-]C(C)C)(C)C.[Li+].IC>CCCCCCC.O.C(OCC)(=O)C>[CH3:1][C:2]1([CH3:31])[C:10]2[CH:9]=[C:8]3[O:11][CH2:12][O:13][C:7]3=[CH:6][C:5]=2[C:4](=[O:14])[N:3]1[CH2:15][CH2:16][CH:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:28])([CH3:27])[CH3:29])=[O:24])[CH2:19][CH2:18]1
Reactant: CC1c2cc3c(cc2C(=O)N1CCC1CCN(C(=O)OC(C)(C)C)CC1)OCO3
Reactant: C1CCOC1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: CI
Solvent: CCCCCCC
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N1CCC(CCN2C(=O)c3cc4c(cc3C2(C)C)OCO4)CC1
Temperature: -12.5 °C
Reaction time: 0.5 h
Yield: 54.2 %

Procedure:
To a reaction vessel, 10 g (0.025 mol) compound XIII and 100 ml tetrahydrofuran were added, stirred, under nitrogen, the mixture was cooled to −10-−15° C., 48 ml (0.096 mol, 2 mol/L) solution of lithium diisopropylamide in n-heptane was added dropwise for about 30 min, after the addition was complete, the reaction was kept for 30 min, and then 1.6 ml (0.026 mol) iodomethane was added dropwise, after the addition was complete, the mixture was warmed to room temperature and then stirred for 1 h, after the reaction was complete, 300 ml ethyl acetate and 150 ml water were added, extracted and washed, the organic layer was collected, dried over sodium sulfate, filtered, the filtrate was concentrated to dry under reduced pressure, separated by column chromatography, and 5.6 g compound XIV was obtained, with yield of 54.2%. MS (ESI): m/z 417 [M+H]+.
Reaction SMILES: S(OOS([O-])(=O)=O)([O-])(=O)=O.[NH4+].[NH4+].[C:13]([CH2:15][CH2:16][CH2:17][C:18](O)=O)#[N:14].[CH3:21][N:22]([CH2:24][C:25]1[CH:30]=C[N:28]=[CH:27][CH:26]=1)[CH3:23].S(=O)(=O)(O)O.N>O.[N+]([O-])([O-])=O.[Ag+]>[C:13]([CH2:15][CH2:16][CH2:17][C:18]1[CH:30]=[C:25]([CH2:24][N:22]([CH3:23])[CH3:21])[CH:26]=[CH:27][N:28]=1)#[N:14]
Reactant: CN(C)Cc1ccncc1
Reactant: N#CCCCC(=O)O
Agent: [Ag+]
Agent: N
Agent: O=S(=O)(O)O
Solvent: O
Product: CN(C)Cc1ccnc(CCCC#N)c1
Temperature: 0 °C
Yield: 36.9 %

Procedure:
Ammonium persulphate (54.8 g) in water (150 ml) and 4-cyanobutyric acid (68 g) in water (300 ml) were added separately and simultaneously over 30 minutes to a mixture of 4-dimethylaminomethylpyridine (16.32 g), silver nitrate (4 g), water (200 ml) and concentrated sulphuric acid (25 ml) stirred at 80°. The reaction mixture was stirred at 80° for 1.5 hours, cooled, poured onto crushed ice (400 g) and aqueous ammonia (28% w/w, 200 ml). The solution was extracted with chloroform (900 ml) and the chloroform extracts were washed with dilute sodium hydroxide, dried over magnesium sulphate, and concentrated in vacuo to give 2-(3-cyanopropyl)-4-dimethylaminomethylpyridine (9 g) as a clear oil b.p. 110°-112°/0.1 mm Hg.
Reaction SMILES: [CH3:1]C(C)([O-])C.[K+].C1COCC1.[I-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Si:33]([O:40][CH:41]1[CH2:52][C:51](=[O:53])[O:50][C@H:49](/[C:54](/[CH3:58])=[CH:55]/[CH:56]=O)[C@@H:48]([CH3:59])[CH:47]=[CH:46][C@@H:45]2[O:60][CH:61]([C:63]3[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=3)[O:62][C@:44]2([CH3:69])[CH2:43][CH2:42]1)([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34]>C(OCC)(=O)C>[Si:33]([O:40][C@H:41]1[CH2:52][C:51](=[O:53])[O:50][C@H:49](/[C:54](/[CH3:58])=[CH:55]/[CH:56]=[CH2:1])[C@@H:48]([CH3:59])[CH:47]=[CH:46][C@@H:45]2[O:60][CH:61]([C:63]3[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=3)[O:62][C@:44]2([CH3:69])[CH2:43][CH2:42]1)([C:36]([CH3:38])([CH3:37])[CH3:39])([CH3:35])[CH3:34]
Reactant: CC(C)(C)[O-]
Reactant: C/C(=C\C=O)[C@H]1OC(=O)CC(O[Si](C)(C)C(C)(C)C)CC[C@@]2(C)OC(c3ccccc3)O[C@H]2C=C[C@@H]1C
Agent: C/C(=C\C=O)[C@H]1OC(=O)CC(O[Si](C)(C)C(C)(C)C)CC[C@@]2(C)OC(c3ccccc3)O[C@H]2/C=C/[C@@H]1C
Agent: C=C/C=C(\C)[C@H]1OC(=O)C[C@H](O[Si](C)(C)C(C)(C)C)CC[C@@]2(C)OC(c3ccccc3)O[C@H]2/C=C/[C@@H]1C
Agent: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: C=C/C=C(\C)[C@H]1OC(=O)C[C@H](O[Si](C)(C)C(C)(C)C)CC[C@@]2(C)OC(c3ccccc3)O[C@H]2C=C[C@@H]1C
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Potassium tert-butoxide (38.2 mg, 0.341 mmol) was added to an anhydrous THF (3 ml) solution of methyltriphenylphosphonium iodide (100 mg, 0.247 mmol) at room temperature, and it was stirred at room temperature for 30 minutes. Subsequently, a THF (3 ml) solution of (3aS,4E,6S,7S,13aR)-11-{[tert-butyl(dimethyl)silyl]oxy}-7-[(E)-2-formyl-1-methyletha-1-en-1-yl]-6,13a-dimethyl-2-phenyl-3a,6,7,10,11,12,13,13a-octahydro-9H-[1,3]dioxolo[4,5-f]oxacyclododecin-9-one (150 mg, 0.284 mmol) was added dropwise to this reaction solution at room temperature and the reaction solution was stirred for one hour. The reaction solution was diluted with ethyl acetate and washed with distilled water and brine. After the organic layer was dried over anhydrous sodium sulfate and the drying agent was filtered off, the organic layer was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (Kanto, commercial name Silica Gel 60N, 40-100 μm; heptane:ethyl acetate=20:1) to obtain the title compound (44 mg) as a white solid. The title compound was determined to be a mixture of a benzylidene acetal and β benzylidene acetal in a ratio of 1:3.2 by 1H-NMR.
Reaction SMILES: [SH:1][CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].CC(C)([O-])C.[K+].Br[CH2:15][C:16](=[CH2:24])[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18]>C(O)C>[CH2:6]([O:5][C:3]([CH2:2][S:1][CH2:24][C:16](=[CH2:15])[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[O:4])[CH3:7]
Reactant: C=C(CBr)C(=O)OC(C)(C)C
Reactant: CCOC(=O)CS
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CCO
Product: C=C(CSCC(=O)OCC)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 61.5 %

Procedure:
To a stirred solution of ethyl α-mercaptoacetate (1.6 g) in ethanol (15 ml), potassium tert-butoxide (1.5 g) was added at -10°-0° C. under nitrogen atmosphere, and the mixture was stirred for 10 minutes at room temperature. Under ice-cooling, tert-butyl 2-bromomethylacrylate (2.9 g) dissolved in ethanol (5 ml) was added to the reaction mixture and the mixture was stirred for 1 hour at room temperature. The reaction mixture was concentrated in vacuo and the residue was dissolved in ethyl acetate. The solution was washed with water and saturated sodium chloride solution, dried over anhydrous sodium sulfate and concentrated in vacuo. The oily residue was purified by a silica gel column chromatography to give 2.1 g (60%) of tert-butyl 2-(ethoxycarbonylmethylthiomethyl)acrylate.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:17]2[O:16][CH:15]([CH2:18][NH:19]C(=O)OCC3C=CC=CC=3)[CH2:14][C:13]=2[CH:12]=[CH:11][CH:10]=1.I[Si](C)(C)C>>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:17]2[O:16][CH:15]([CH2:18][NH2:19])[CH2:14][C:13]=2[CH:12]=[CH:11][CH:10]=1
Reactant: O=C(NCC1Cc2cccc(-c3ccc(Cl)cc3Cl)c2O1)OCc1ccccc1
Agent: C[Si](C)(C)I
Product: NCC1Cc2cccc(-c3ccc(Cl)cc3Cl)c2O1
Yield: 81.8 %

Procedure:
Treatment of (−)-benzyl {[7-(2,4-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}carbamate (1.85 g, 4.32 mmol) with iodotrimethylsilane (3.45 g, 17.28 mmol) generally according to the procedure described for Example 129 gave 1.04 g (82%) of (+)-1-[7-(2,4-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt. [α]D25=+2.7 (c 10.0 in dimethylsulfoxide); mp 201-204° C.; Anal. calcd. for C15H13Cl2NOHCl: C, 54.59; H, 4.27; N, 4.24. Found: C, 54.25; H, 4.12; N, 4.16.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH2:10][C:11](=O)[CH3:12])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].[ClH:14].C(N)C.C([N:20]([CH2:23][CH3:24])CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl>ClCCl.C(OCC)C.CO>[ClH:14].[CH3:12][CH:11]([CH2:24][CH2:23][NH2:20])[CH2:10][C:6]1[CH:7]=[CH:8][CH:9]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=1
Reactant: CC(=O)Cc1cccc([N+](=O)[O-])c1
Reactant: CCN(CC)CC
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: CCN
Agent: Cl
Solvent: CCOCC
Solvent: ClCCl
Solvent: CO
Product: CC(CCN)Cc1cccc([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 71.5 %

Procedure:
In dichloromethane (50 ml) was combined 1-(3-nitrophenyl)propan-2-one (1.44 grams, 8 mmole), ethylamine hydrochloride (0.42 grams, 8 mmole), and triethylamine (1.1 ml, 11 mmole). The mixture was stirred under nitrogen at room temperature for 30 minutes. Then sodium triacetoxyborohydride (2.5 grams, 11.7 mmole) was added in one portion. The mixture was stirred under nitrogen 18 hours. Additional ethylamine hydrochloride (0.4 grams) was added. After another 18 hours the mixture was diluted with ethyl ether, washed with 10% sodium hydroxide solution (50 ml), dried over anhydrous magnesium sulfate and the solvent removed under vacuum to give an oil. This oil was taken up into methanol, acidified with 1M hydrochloric acid in ether and the salt was precipitated by further addition of ether. The resulting solid was filtered and air dried to give [2-(1-methyl-2-(3-nitrophenyl)ethyl]ethylamine hydrochloride (1.4 grams, 85%), m.p. 173-175° C., M+H 208.
Reaction SMILES: [NH2:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5]([OH:18])=[CH:4][C:3]=1[O:19][C:20]1C=CC=C[CH:21]=1.[CH3:26][CH:27](CCO)[CH2:28][CH2:29][OH:30].C(=O)([O-])[O-].[K+].[K+]>CN1CCCC1=O>[NH2:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5]([OH:18])=[CH:4][C:3]=1[O:19][CH2:20][CH2:21][CH:27]([CH3:26])[CH2:28][CH2:29][OH:30]
Reactant: CC(CCO)CCO
Reactant: Nc1c(Oc2ccccc2)cc(O)c2c1C(=O)c1ccccc1C2=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN1CCCC1=O
Product: CC(CCO)CCOc1cc(O)c2c(c1N)C(=O)c1ccccc1C2=O

Procedure:
12.5 parts of 1-amino-2-phenoxy-4-hydroxyanthraquinone, 13 parts of 3-methyl-1,5-pentanediol, 25 parts of N-methylpyrrolidone, 3 parts of polyethylene oxide of average molecular weight 300 and 2 parts of anhydrous potassium carbonate are stirred for one hour at 150°C under nitrogen. After working up, 10.5 parts of 1-amino-2-(3'-methyl-5'-hydroxypentanoxy)-4-hydroxyanthraquinone are obtained.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[CH:8]=[CH:9][C:10]3[O:19][CH2:18][CH2:17][C:16]4[N:12]([N:13]=[C:14]([C:20]5[N:21]([CH2:25][C:26]([F:29])([F:28])[F:27])[N:22]=[CH:23][N:24]=5)[CH:15]=4)[C:11]=3[CH:30]=2)[CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:38][CH2:39][O:40]C1CCCCO1.Cl>CN(C=O)C.CO>[F:28][C:26]([F:29])([F:27])[CH2:25][N:21]1[C:20]([C:14]2[CH:15]=[C:16]3[N:12]([C:11]4[CH:30]=[C:7]([CH:4]5[CH2:3][CH2:2][N:1]([CH2:38][CH2:39][OH:40])[CH2:6][CH2:5]5)[CH:8]=[CH:9][C:10]=4[O:19][CH2:18][CH2:17]3)[N:13]=2)=[N:24][CH:23]=[N:22]1
Reactant: FC(F)(F)Cn1ncnc1-c1cc2n(n1)-c1cc(C3CCNCC3)ccc1OCC2
Reactant: BrCCOC1CCCCO1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CO
Product: OCCN1CCC(c2ccc3c(c2)-n2nc(-c4ncnn4CC(F)(F)F)cc2CCO3)CC1
Temperature: 50 °C
Reaction time: 2 h
Yield: 57.8 %

Procedure:
A mixture of 9-piperidin-4-yl-2-[2-(2,2,2-trifluoro-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1,10b-diaza-benzo[e]azulene (180 mg, 0.43 mmol) in DMF (1 mL), potassium carbonate (89 mg, 0.65 mmol) and 2-(2-bromo-ethoxy)-tetrahydro-pyran (97 L, 0.65 mmol) was heated at 50° C. for 18 h. The cooled reaction mixture was partitioned between ethyl acetate and water, the aqueous layer extracted with ethyl acetate and the combined organic extracts dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0 to 10% MeOH (+2M NH3) in DCM) to give a colourless oil. The oil was dissolved in methanol and treated with 1M HCl in methanol (2 mL, 2 mmol) and the reaction mixture stirred for 2 h at RT before concentrating in vacuo. The resultant residue was triturated in a mixture of diethyl ether and methanol to give 142 as a pale yellow solid (115 mg, 54%). 1H NMR (DMSO-d6, 400 MHz): δ 9.81 (br s, 1 H); 8.22 (s, 1 H); 7.70 (s, 1 H); 7.32-7.24 (m, 2 H); 6.99 (s, 1 H); 5.72 (q, J=8.7 Hz, 2 H); 5.36 (br s, 1 H); 4.51 (t, J=6.0 Hz, 2 H); 3.80 (t, J=4.9 Hz, 2 H); 3.67-3.57 (m, 2 H); 3.22-3.06 (m, 6 H); 2.97-2.85 (m, 1 H); 2.10-2.00 (m, 4 H). LCMS: RT=6.62 min, M+H+=463.1
Reaction SMILES: [F:1][C:2]([F:16])([F:15])[C:3]1[N:7]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)[N:6]=[CH:5][CH:4]=1.Cl.Cl[CH2:19][CH2:20][N:21]1[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1>>[F:16][C:2]([F:1])([F:15])[C:3]1[N:7]([C:8]2[CH:9]=[CH:10][C:11]([O:14][CH2:19][CH2:20][N:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]3)=[CH:12][CH:13]=2)[N:6]=[CH:5][CH:4]=1
Reactant: ClCCN1CCCCC1
Reactant: Oc1ccc(-n2nccc2C(F)(F)F)cc1
Agent: Cl
Product: FC(F)(F)c1ccnn1-c1ccc(OCCN2CCCCC2)cc1
Yield: 48 %

Procedure:
The title compound was prepared from 4-(5-trifluoromethyl-pyrazol-1-yl)phenol (0.1 g, 0.43 mmol), 1-(2-chloroethyl)piperidine hydrochloride (0.16 g, 0.88 mmol) using the general procedure C with a yield of 48% (70 mg); 1H NMR (400 MHz, CDCl3) 7.84 (d, J=2 Hz, 1H), 7.58 (d, J=9.2 Hz, 2H), 6.98 (d, J=9.2 Hz, 2H), 6.65 (d, J=1.6 Hz, 1H), 4.14 (t, J=12, 6 Hz, 2H), 2.78 (t, J=12, 6 Hz, 2H), 2.53 (br, 4H), 1.61-1.47 (m, 6H); LC/MS (ESI): 94%.
Reaction SMILES: Cl[C:2]1[N:3]=[C:4]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[C:5]2[S:10][C:9]([C:11]([OH:14])([CH3:13])[CH3:12])=[N:8][C:6]=2[N:7]=1.C(=O)([O-])[O-].[Na+].[Na+].[C:27](#[N:29])[CH3:28]>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>[NH2:7][C:2]1[N:3]=[CH:4][C:28]([C:2]2[N:3]=[C:4]([N:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)[C:5]3[S:10][C:9]([C:11]([OH:14])([CH3:13])[CH3:12])=[N:8][C:6]=3[N:7]=2)=[CH:27][N:29]=1
Reactant: CC(C)(O)c1nc2nc(Cl)nc(N3CCOCC3)c2s1
Reactant: CC#N
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Product: CC(C)(O)c1nc2nc(-c3cnc(N)nc3)nc(N3CCOCC3)c2s1

Procedure:
2-(5-Chloro-7-morpholinothiazolo[4,5-d]pyrimidin-2-yl)propan-2-ol, 5-pyrimidine-2-amine boronic acid (1.2 eq), and trans-dichlorobis(triphenylphosphine)palladium(II) (0.1 eq) were slurried with equal parts 1M sodium carbonate aqueous solution (3 eq) and acetonitrile. The solution was microwaved at 130° C. for 15 minutes. The solution was evaporated to dryness and purified by reverse phase silica gel chromatography to give the product 137.
Reaction SMILES: [Li][CH2:2][CH2:3][CH2:4][CH3:5].[C:6]([N:13]1[C@@H:18]([CH:19]=O)[CH2:17][CH2:16][CH2:15][C@@H:14]1[CH3:21])([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7].CCOC(C)=O.CCCCCC>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1.O>[C:6]([N:13]1[C@@H:14]([CH3:21])[CH2:15][CH2:16][CH2:17][C@@H:18]1[CH:19]=[CH:2][CH2:3][CH2:4][CH3:5])([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7]
Reactant: C[C@H]1CCC[C@H](C=O)N1C(=O)OC(C)(C)C
Reactant: [Li]CCCC
Agent: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Solvent: C1CCOC1
Solvent: O
Solvent: CCCCCC
Product: CCCC=C[C@H]1CCC[C@H](C)N1C(=O)OC(C)(C)C
Temperature: -30 °C
Reaction time: 0.5 h
Yield: 100 %

Procedure:
A suspension of methyltriphenylphosphonium bromide (5.29 g, 13.25 mmol) in 27 mL of THF was cooled to −30° C. and treated with n-BuLi (6.13 mL, 13.44 mmol) dropwise. The deep red solution was slowly warmed to 0° C., stirred for 30 min, and then cooled to −78° C. The ylide was treated with a solution of trans-N-Boc-2-Methyl-6-Piperidinecarboxaldehyde (2.00 g, 9.46 mmol) in 3 mL of THF, and the mixture was slowly warmed to room temperature. The mixture was diluted with water, and the organic layer was separated. The aqueous layer was extracted with ether and the combined extracts were dried over K2CO3 and then concentrated to give a crude product as an oil. Chromatography on silica with 5% EtOAc/hexane afforded 2.53 g (87%) of the product which was homogeneous by TLC analysis. 1H NMR (250 MHz) δ5.48-5.28 (m, 2 H), 4.58-4.54 (m, 1 H), 4.06-4.03 (m, 1 H), 2.10-1.23 (m, 19 H), 1.22-1.18 (d, 3 H), 0.93-0.88 (t, 3 H); , 1 H), 4.07-4.00 (m, 1 H), 2.12-1.38 (m, 15 H), 1.23-1.19 (d, 3 H), 0.97-0.95 (t, 3 H); 13C NMR (62.7 MHz) 155.5 (s), 132.4 (s), 129.2 (s), 78.9 (s), 49.1 (s), 47.5 (s), 29.4 (s), 28.5 (s), 28.2 (s), 27.8 (s), 22.8 (s), 20.2 (s), 15.0 (s), 13.9 (s) ppm.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5](/[CH:13]=[CH:14]\[C:15]2[C:20]([O:21][Si](C(C)(C)C)(C)C)=[C:19]([O:29][Si](C(C)(C)C)(C)C)[CH:18]=[CH:17][CH:16]=2)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].C(O)(=O)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O>C1COCC1>[CH3:12][O:11][C:7]1[CH:6]=[C:5](/[CH:13]=[CH:14]\[C:15]2[C:20]([OH:21])=[C:19]([OH:29])[CH:18]=[CH:17][CH:16]=2)[CH:4]=[C:3]([O:2][CH3:1])[C:8]=1[O:9][CH3:10]
Reactant: COc1cc(/C=C\c2cccc(O[Si](C)(C)C(C)(C)C)c2O[Si](C)(C)C(C)(C)C)cc(OC)c1OC
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: CC(=O)O
Solvent: O
Product: COc1cc(/C=C\c2cccc(O)c2O)cc(OC)c1OC
Reaction time: 1 h
Yield: 94.3 %

Procedure:
A solution of 8 (0.106 g, 0.2 mmol) in 2 mL THF was stirred at 0° while adding acetic acid (0.024 g, 0.4 mmol) and tetrabutylammonium fluoride (1M in THF, 0.4 ml, 0.4 mmol). The solution was stirred at 20° for one hour then cooled to 0° and 0.5 mL water added. The mixture was extracted with TBME three times, dried, evaporated and the residue partitioned between 10 mL heptane/10 mL acetonitrile. Evaporation of the acetonitrile layer gave 0.057 g pale yellow gum which was purified by silica chromatography with 7:3 heptane:ethyl acetate to give ZSB-82 as a colourless gum (0.032 g):
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:12]#[C:13][CH2:14]O)[CH:6]=[CH:7][C:8]=1[N+:9]([O-:11])=[O:10].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1C(=O)N([Cl:42])C(=O)C1>C(Cl)Cl>[Cl:42][CH2:14][C:13]#[C:12][C:5]1[CH:6]=[CH:7][C:8]([N+:9]([O-:11])=[O:10])=[C:3]([O:2][CH3:1])[CH:4]=1
Reactant: O=C1CCC(=O)N1Cl
Reactant: COc1cc(C#CCO)ccc1[N+](=O)[O-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: COc1cc(C#CCCl)ccc1[N+](=O)[O-]
Reaction time: 1 h
Yield: 97.5 %

Procedure:
To 3-[3-(methyloxy)-4-nitrophenyl]-2-propyn-1-ol (1.6 g, 7.72 mmol) in 75 mL of DCM was added, triphenylphosphine (2.7 g, 10.27 mmol), and NCS (1.37 g, 10.27 mmol). The mixture stirred for 1 h. 10 g of silica gel was added. The solvent was rotovaped down and the pre-adsorbed solids were purified by flash chromatography to give the title compound of step B (1.7 g, 7.53 mmol, 97%). 1H NMR (400 MHz, CDCl3) δ ppm 7.80 (d, J=8.42 Hz, 1H), 7.13 (d, J=1.47 Hz, 1H), 7.08 (dd, J=8.33, 1.56 Hz, 1H), 4.37 (s, 2 H), 3.95 (s, 3H).
Reaction SMILES: [CH2:1]([C:5]1[N:6]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[N:33]3[N:37]=[CH:36][O:35][C:34]3=[S:38])=[CH:23][CH:22]=2)[C:7]([CH2:11][O:12][Si](C(C)(C)C)(C)C)=[C:8]([Cl:10])[N:9]=1)[CH2:2][CH2:3][CH3:4].C(#N)C.C([O-])(O)=O.[Na+]>O>[CH2:1]([C:5]1[N:6]([CH2:20][C:21]2[CH:22]=[CH:23][C:24]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[N:33]3[N:37]=[CH:36][O:35][C:34]3=[S:38])=[CH:25][CH:26]=2)[C:7]([CH2:11][OH:12])=[C:8]([Cl:10])[N:9]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1nc(Cl)c(CO[Si](C)(C)C(C)(C)C)n1Cc1ccc(-c2ccccc2-n2ncoc2=S)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CC#N
Product: CCCCc1nc(Cl)c(CO)n1Cc1ccc(-c2ccccc2-n2ncoc2=S)cc1
Yield: 50 %

Procedure:
A solution of 5-[4'-[[2-butyl-4-chloro-5-(t-butyldimethylsilyloxymethyl)-1H-imidazol-1-yl]methyl][1,1'-biphenyl-2-yl]-1,3,4-oxadiazol-2[3H]-thione (100 mg) in 1:9 48% HF/acetonitrile (10 mL) was stirred at room temperature for 3 hours in a plastic flask. The reaction mixture was neutralized by the dropwise addition of saturated aqueous NaHCO3 (to pH 5) and was diluted with water. The resulting precipitate was collected by filtration and washed with water. Recrystallization from ethyl acetate gave pure 5-[4'-[[2-butyl-4-chloro-5-(hydroxymethyl)1H imidazol-1-yl]methyl][1,1'-biphenyl-2-yl]-1,3,4-oxadiazol-2[3H]-thione (40 mg, 50%), mp 193°-194° C. dec.