Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3](=[O:15])[C:4](=[N+]=[N-])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][CH:7]=1.[CH:16]1([CH2:20][OH:21])[CH2:19][CH2:18][CH2:17]1>C1C=CC=CC=1>[Cl:12][C:9]1[CH:10]=[CH:11][C:6]([CH2:5][CH:4]([O:21][CH2:20][CH:16]2[CH2:19][CH2:18][CH2:17]2)[C:3]([O:2][CH3:1])=[O:15])=[CH:7][CH:8]=1
Reactant: COC(=O)C(Cc1ccc(Cl)cc1)=[N+]=[N-]
Reactant: OCC1CCC1
Solvent: c1ccccc1
Product: COC(=O)C(Cc1ccc(Cl)cc1)OCC1CCC1
Temperature: 90 °C

Procedure:
To a solution of 500 mg (2.23 mmol) of methyl-2-diazo-3-(4-chlorophenyl)propanoate (obtained from Step A) and 1.05 mL (5 eq; 11.1 mmol) of cyclobutanemethanol in 5 mL benzene in a pressure tube was added 10 mg (1 mole %) of Rh2(OAc)4 catalyst. The tube was sealed and heated to 90° C. for 1.5 h. The solvents were evaporated under reduced pressure and the crude material was taken up in CH2Cl2 and purified by flash chromatography via gradient elution using mixtures of hexane and EtOAc (100:1 to 50:1). This provided the title compound as a clear oil. TLC Rf=0.53 (4:1 hexanes:EtOAc). 500 MHz 1H NMR (CDCl3): δ 1.68 (m, 2H); 1.85 (m, 1H); 1.88 (m, 1H); 2.01 (m, 2H); 2.53 (sep, 1H); 2.98 (m, 2H); 3.24 (dd, 1H); 3.58 (dd, 1H); 3.76 (s, 3H); 3.98 (dd, 1H); 7.20 (d, 2H); 7.28 (d, 2H).
Reaction SMILES: F[B-](F)(F)F.[F:6][S:7]([F:19])([F:18])([F:17])([F:16])[C:8]1[CH:13]=[CH:12][C:11]([N+]#N)=[CH:10][CH:9]=1.[C:20]1([C:26]#[CH:27])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.[I-].[Na+].C(N(CC)CC)C>C(O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[F:6][S:7]([F:19])([F:18])([F:17])([F:16])[C:8]1[CH:13]=[CH:12][C:11]([C:27]#[C:26][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:10][CH:9]=1
Reactant: C#Cc1ccccc1
Reactant: N#[N+]c1ccc(S(F)(F)(F)(F)F)cc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: F[B-](F)(F)F
Solvent: CCN(CC)CC
Solvent: CCO
Product: FS(F)(F)(F)(F)c1ccc(C#Cc2ccccc2)cc1
Temperature: 70 °C
Reaction time: 22 h
Yield: 8.9 %

Procedure:
(Bowden, et al., Tetrahedron 2000, 56, 3393-3408) Diazonium salt 1 (11.7 mg, 0.0368 mmol) was added to a mixture of phenylacetylene (11.4 mg, 0.0805 mmol), sodium iodide (9.8 mg, 0.065 mmol), and Pd(OAc)2 (0.5 mg, 0.002 mmol) in 0.23 g of 95% ethanol. Then triethylamine (10.6 mg, 0.077 mmol) was added to the mixture. The reaction mixture was stirred at 70° C. for 22 h, then filtered through a pad of SiO2 with the help of hexane. Removal of the solvent gave a pale yellow crystalline solid which were purified by SiO2 column chromatography with hexane to give 24a as a colorless oil (1.0 mg; 9%); m.p. 88.0-89.0° C. IR (ATR): {tilde over (v)}=2926, 2222, 1603, 1503, 1445, 1402, 1094, 835 cm−1. MS (GC, EI): m/z=304 [M+], 196. 1H NMR (500 MHz, CDCl3): δ=7.74 (d, J=9.0 Hz, 2H), 7.60 (d, J=9.0 Hz, 2H), 7.55 (m, 2H), 7.39-7.37 (m, 3H) ppm. 13C NMR (125 MHz, CDCl3): δ=153.0 (C), 131.8 (2CH), 131.6 (2CH), 129.0 (CH), 128.5 (2CH), 127.0 (C), 126.0 (2CH), 122.2 (C), 92.2 (C), 87.2 (C) ppm. 19F NMR (470 MHz, CDCl3): δ=84.0 (quint, J=150 Hz, 1 F), 62.7 (d, J=150 Hz, 4 F) ppm.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:9](=[N:10][C:11]=1[N:12]1[CH2:17][CH2:16][N:15]([C:18](=[O:23])[C:19]([F:22])([F:21])[F:20])[CH2:14][CH2:13]1)[NH:8][CH:7]=[C:6]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[C:5]2=[O:29].[CH2:30](I)[CH3:31].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH2:30]([N:8]1[C:9]2[C:4](=[CH:3][C:2]([F:1])=[C:11]([N:12]3[CH2:13][CH2:14][N:15]([C:18](=[O:23])[C:19]([F:21])([F:20])[F:22])[CH2:16][CH2:17]3)[N:10]=2)[C:5](=[O:29])[C:6]([C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:7]1)[CH3:31]
Reactant: CCI
Reactant: CCOC(=O)c1c[nH]c2nc(N3CCN(C(=O)C(F)(F)F)CC3)c(F)cc2c1=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)c1cn(CC)c2nc(N3CCN(C(=O)C(F)(F)F)CC3)c(F)cc2c1=O

Procedure:
Ethyl 6-fluoro-1,4-dihydro-4-oxo-7-(4-trifluoroacetyl-1-piperazinyl)-1,8-naphthyridine-3-carboxylate was treated with ethyl iodide and potassium carbonate in dimethyl formamide by the same procedure as described in Example 1 to form ethyl 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(4-trifluoroacetyl-1-piperazinyl)-1,8-naphthyridine-3-carboxylate. This product was hydrolyzed by treating with aqueous potassium carbonate in a mixture of chloroform and methanol to give ethyl 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-1,8-naphthyridine-3-carboxylate, m.p. 150°-151° C.
Reaction SMILES: Cl[C:2]1[N:3]=[C:4]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[C:5]2[CH:10]=[C:9]([CH2:11][N:12]3[CH2:17][CH2:16][N:15]([C:18](=[O:21])[CH2:19][OH:20])[CH2:14][CH2:13]3)[S:8][C:6]=2[N:7]=1.CC1(C)C(C)(C)OB([C:36]2[CH:37]=[CH:38][C:39]([NH2:42])=[N:40][CH:41]=2)O1>>[NH2:42][C:39]1[N:40]=[CH:41][C:36]([C:2]2[N:3]=[C:4]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[C:5]3[CH:10]=[C:9]([CH2:11][N:12]4[CH2:17][CH2:16][N:15]([C:18](=[O:21])[CH2:19][OH:20])[CH2:14][CH2:13]4)[S:8][C:6]=3[N:7]=2)=[CH:37][CH:38]=1
Reactant: CC1(C)OB(c2ccc(N)nc2)OC1(C)C
Reactant: O=C(CO)N1CCN(Cc2cc3c(N4CCOCC4)nc(Cl)nc3s2)CC1
Product: Nc1ccc(-c2nc(N3CCOCC3)c3cc(CN4CCN(C(=O)CO)CC4)sc3n2)cn1

Procedure:
1-(4-((2-Chloro-4-morpholinothieno[2,3-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-hydroxyethanone (265 mg) was reacted with 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine via General Procedure A to give 16.5 mg of 181. MS (Q1) 470.2 (M)+
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[NH:21]C2C=CC=CC=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)(=[O:3])[CH3:2].[Br:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[N:35]=[C:36]=[O:37]>>[C:1]([NH:4][C:5]1[CH:6]=[CH:7][C:8]([S:11]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[NH:21][C:36]([NH:35][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=2[Br:28])=[O:37])(=[O:13])=[O:12])=[CH:9][CH:10]=1)(=[O:3])[CH3:2]
Reactant: O=C=Nc1ccccc1Br
Reactant: CC(=O)Nc1ccc(S(=O)(=O)Nc2ccccc2Nc2ccccc2)cc1
Product: CC(=O)Nc1ccc(S(=O)(=O)Nc2ccccc2NC(=O)Nc2ccccc2Br)cc1
Yield: 23.8 %

Procedure:
The urea was synthesized from 2-[(4-acetamidophenyl)sulfonylamino]phenyl aniline(1 mmol) and 2-bromo phenyl isocyanate(1 mmol) by general Method B. It was purified by dilution with methylene chloride and precipitation with hexane. Filtering afforded the desired compound(0.12 g, 24%). EI-MS m/z 501(M-H)-
Reaction SMILES: C(OC([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C:13](=[O:26])[NH:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([O:21][C:22]([F:25])([F:24])[F:23])[CH:16]=1)=O)(C)(C)C.[C:27]([OH:33])([C:29]([F:32])([F:31])[F:30])=[O:28]>C(Cl)Cl>[F:24][C:22]([F:23])([F:25])[O:21][C:17]1[CH:16]=[C:15]([NH:14][C:13]([C@@H:9]2[CH2:10][CH2:11][CH2:12][NH:8]2)=[O:26])[CH:20]=[CH:19][CH:18]=1.[C:27]([OH:33])([C:29]([F:32])([F:31])[F:30])=[O:28]
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1C(=O)Nc1cccc(OC(F)(F)F)c1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C(Nc1cccc(OC(F)(F)F)c1)[C@@H]1CCCN1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To a solution of (S)-2-(3-trifluoromethoxy-phenylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (8.52 g, 22.6 mmol) in CH2Cl2 (50 mL) was added TFA (8.65 mL, 113 mmol) and solution was stirred at RT for 12 h. The crude reaction mixture was concentrated under vacuum, Et2O was added and the white precipitate was filtered off to give the desired compound as a TFA salt. MS (LC/MS): 275.2 [M+H]+, 273.3 [M−H]−; tR (HPLC conditions a) 2.47 min.
Reaction SMILES: [NH:1]1[CH:5]=[C:4]([C:6]2[N:11]=[C:10]3[N:12]([CH2:15][C:16]4[CH:17]=[C:18]5[C:23](=[CH:24][CH:25]=4)[N:22]=[CH:21][CH:20]=[CH:19]5)[N:13]=[N:14][C:9]3=[N:8][CH:7]=2)[CH:3]=[N:2]1.C([O-])([O-])=O.[Cs+].[Cs+].[CH3:32][C:33]1([CH3:36])[CH2:35][O:34]1>CN(C=O)C>[CH3:32][C:33]([OH:34])([CH3:36])[CH2:35][N:2]1[CH:3]=[C:4]([C:6]2[N:11]=[C:10]3[N:12]([CH2:15][C:16]4[CH:17]=[C:18]5[C:23](=[CH:24][CH:25]=4)[N:22]=[CH:21][CH:20]=[CH:19]5)[N:13]=[N:14][C:9]3=[N:8][CH:7]=2)[CH:5]=[N:1]1
Reactant: CC1(C)CO1
Reactant: c1cnc2ccc(Cn3nnc4ncc(-c5cn[nH]c5)nc43)cc2c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CC(C)(O)Cn1cc(-c2cnc3nnn(Cc4ccc5ncccc5c4)c3n2)cn1
Temperature: 80 °C
Reaction time: 16 h
Yield: 22 %

Procedure:
To a suspension of 6-[6-(1H-pyrazol-4-yl)-[1,2,3]triazolo[4,5-b]pyrazin-1-ylmethyl]-quinoline (50 mg, 0.15 mmol) and Cs2CO3 (50 mg, 0.15 mmol) in DMF (2 mL) was added 2,2-dimethyl-oxirane. The reaction was stirred at 80° C. for 16 hours. The reaction was then purified with a reverse-phased preparative HPLC eluting with acetonitrile-water having 0.1% acetic acid to yield 2-methyl-1-[4-(3-quinolin-6-ylmethyl-3H-[1,2,3]triazolo[4,5-b]pyrazin-5-yl)-pyrazol-1-yl]-propan-2-ol (13 mg, 22% yield).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([S:12]([NH:15][C@H:16]2[CH2:21][CH2:20][CH2:19][C@@H:18]([N:22]3[CH:26]=[N:25][N:24]=[CH:23]3)[CH2:17]2)(=[O:14])=[O:13])[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[CH2:27]([O:31]C=C)[CH2:28]CC.C(N(CC)CC)C>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:27]([C:2]1[CH:3]=[C:4]([S:12]([NH:15][C@H:16]2[CH2:21][CH2:20][CH2:19][C@@H:18]([N:22]3[CH:26]=[N:25][N:24]=[CH:23]3)[CH2:17]2)(=[O:14])=[O:13])[CH:5]=[C:6]([C:8]([F:11])([F:9])[F:10])[CH:7]=1)(=[O:31])[CH3:28]
Reactant: C=COCCCC
Reactant: O=S(=O)(N[C@H]1CCC[C@@H](n2cnnc2)C1)c1cc(Br)cc(C(F)(F)F)c1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CC(=O)c1cc(C(F)(F)F)cc(S(=O)(=O)N[C@H]2CCC[C@@H](n3cnnc3)C2)c1
Temperature: 80 °C
Reaction time: 6 h

Procedure:
Palladium acetate (9.9 mg, 0.044 mmol) was added to a stirred solution of 3a (100 mg, 0.221 mmol), n-butylvinyl ether (221 mg, 2.206 mmol) and triethylamine (92.0 μL, 0.662 mmol) in DMF (2.00 mL), and the resulting mixture was degassed and heated to 80° C. After 6 h, the reaction mixture was cooled to 0° C., 1M HCl was added, and the resulting mixture was allowed to warm to rt and stirred overnight. The reaction mixture was quenched with satd. aq. NaHCO3 and extracted with EtOAc. The combined organics were dried (MgSO4), filtered and concentrated in vacuo. The crude residue was purified by preparative thin layer chromatography on silica gel (10% MeOH/DCM as eluent) to afford the title compound, 9a. m/z (ES) 417 (MH)+
Reaction SMILES: [CH3:1][C:2]1([CH3:15])[O:11][C:10]2[C:5](=[CH:6][C:7]([C:12]#[N:13])=[CH:8][CH:9]=2)[CH:4]2[O:14][CH:3]12.[CH2:16]([O:18][C:19]1[CH:20]=[CH:21][C:22]2[S:26][C:25]([NH2:27])=[N:24][C:23]=2[CH:28]=1)[CH3:17]>>[CH2:16]([O:18][C:19]1[CH:20]=[CH:21][C:22]2[S:26][C:25]([NH:27][CH:4]3[C:5]4[C:10](=[CH:9][CH:8]=[C:7]([C:12]#[N:13])[CH:6]=4)[O:11][C:2]([CH3:15])([CH3:1])[CH:3]3[OH:14])=[N:24][C:23]=2[CH:28]=1)[CH3:17]
Reactant: CC1(C)Oc2ccc(C#N)cc2C2OC21
Reactant: CCOc1ccc2sc(N)nc2c1
Product: CCOc1ccc2sc(NC3c4cc(C#N)ccc4OC(C)(C)C3O)nc2c1

Procedure:
Following the procedure in Example 1, using (±)-2,2-dimethyl-1a,7b-dihydro-2H-1,3-dioxa-cyclopropa[a]naphthalene-6-carbonitrile and 5-ethoxy-benzothiazol-2-ylamine as starting material, the title compound was prepared as a white solid.
Reaction SMILES: [Mg].C[SiH](OC(C)(C)C)C.Br[C:11]1[CH:16]=[CH:15][C:14]([CH2:17][CH2:18][OH:19])=[CH:13][CH:12]=1.BrC(Br)C.[B:24](OC)([O:27]C)[O:25]C.Cl>O1CCCC1>[OH:19][CH2:18][CH2:17][C:14]1[CH:15]=[CH:16][C:11]([B:24]([OH:27])[OH:25])=[CH:12][CH:13]=1
Reactant: COB(OC)OC
Reactant: OCCc1ccc(Br)cc1
Agent: CC(Br)Br
Agent: C[SiH](C)OC(C)(C)C
Agent: Cl
Solvent: C1CCOC1
Product: OCCc1ccc(B(O)O)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a suspension of magnesium (0.264 g, 11 mmol) in dry tetrahydrofuran (10 ml) under nitrogen gas was added dropwise over 1/2 hour the t-butyl dimethyl silyl ether of 4-bromophenyl ethyl alcohol (a, 3.45 g, 10.9 mmol) in tetrahydrofuran (10 ml). Magnesium was then activated by the addition of dibromoethane (0.1 g). The metal went into solution slowly over a period of 8 hours. The Grignard reagent was then cooled to -78° C. and treated with freshly distilled trimethyl borate (1.15 g, 11 mmol) added dropwise with stirring. The reaction mixture was then warmed to room temperature and stirred overnight. It was then treated with 2N hydrochloric acid till acidic and the tetrahydrofuran layer was separated from the aqueous layer. The aqueous portion was thoroughly extracted with ethyl acetate (5×50 ml) and the combined organic layer was washed with water and finally with saturated sodium chloride. The organic phase was then dried, concentrated and the residue was purified by chromatography (silica gel). Elution with ethyl acetate/methanol (95:5) provided the boronic acid, which was recrystallized from ethyl acetate/hexane. Yield: 0.69 g (38%), m.p. 218°-220° C., M.S. 184 (M+NH4), 156, 140, 1H NMR (DMSO-d6): δ2.7 (t, 2H), 4.6 (t, 2H), 7.1 and 7.7 (2d, 4H) and 7.9 (s, 2H).
Reaction SMILES: [CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].C[CH:8]([OH:10])[CH3:9]>C(Cl)(Cl)Cl>[C:3]1([C@H:9]2[CH2:8][O:10]2)[CH:2]=[CH:1][CH:6]=[CH:5][CH:4]=1
Reactant: CCCCCC
Reactant: CC(C)O
Solvent: ClC(Cl)Cl
Product: c1ccc([C@H]2CO2)cc1
Yield: 69 %

Procedure:
Colorless oily substance, 69% yield, >99% ee (CHIRALCEL OD-H, hexane/iPrOH 99.9:0.1); [α]D23 +26.1° (c=0.48, CHCl3); 1H NMR (CDCl3): δ7.39-7.26 (m, 5H), 3.88-3.85 (dd, J=2.6, 4.0 Hz, 1H), 3.17-3.13 (dd, J=4.0, 5.6 Hz, 1H), 2.82-2.79 ppm (dd, J=2.6, 5.6 Hz, 1H).
Reaction SMILES: C([N:8](CC1C=CC=CC=1)[S:9]([C:12]1[CH:13]=[CH:14][C:15]2[CH:23]=[CH:22][C:21]3[N:20]([C:24](=[O:29])[C:25]([F:28])([F:27])[F:26])[CH2:19][CH:18](CCl)[C:17]=3[C:16]=2[CH:32]=1)(=[O:11])=[O:10])C1C=CC=CC=1.CCOC(C)=O>OS(O)(=O)=O>[F:28][C:25]([F:26])([F:27])[C:24]([N:20]1[C:21]2[CH:22]=[CH:23][C:15]3[CH:14]=[CH:13][C:12]([S:9]([NH2:8])(=[O:10])=[O:11])=[CH:32][C:16]=3[C:17]=2[CH2:18][CH2:19]1)=[O:29]
Reactant: O=C(N1CC(CCl)c2c1ccc1ccc(S(=O)(=O)N(Cc3ccccc3)Cc3ccccc3)cc21)C(F)(F)F
Agent: O=S(=O)(O)O
Solvent: CCOC(C)=O
Product: NS(=O)(=O)c1ccc2ccc3c(c2c1)CCN3C(=O)C(F)(F)F
Temperature: 0 °C
Reaction time: 2 h
Yield: 108.6 %

Procedure:
Sulfonamide 215 (750 mg, 1.31 mmol) was cooled to 0° C., dissolved in conc. H2SO4 (20 mL) at 0° C., and the solution was stirred at this temperature for 2 h. Ice water and EtOAc were added and the mixture was extracted with EtOAc (×3). The combined extracts were washed with brine (×3), dried, and evaporated to give 1-chloromethyl)-3-(trifluoroacetyl)-1,2-dihydro-3H-benzo[e]indole-8-sulfonamide (216) (490 mg, 96%). A sample was recrystallised from CH2Cl2/EtOAc as yellow crystals: mp 229-231° C.; 1H NMR [(CD3)2SO] δ 8.45 (d, J=9.0 Hz, 1H), 8.42 (s, 1H), 8.21 (d, J=8.7 Hz, 1H), 8.11 (d, J=9.0 Hz, 1H), 7.87 (dd, J=8.7, 1.7H, 1H), 7.51 (s, 2H), 4.65-4.57 (m, 1H), 4.57-4.50 (m, 1H), 4.44 (d, J=10.8 Hz, 1H), 4.18 (dd, J=11.3, 3.1 Hz, 1H), 4.05 (dd, J=11.3, 5.9 Hz, 1H). Anal. (C15H12ClF3N2O3S.½H2O) C, H, N.
Reaction SMILES: Br[C:2]1[N:6]([S:7]([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)(=[O:9])=[O:8])[CH:5]=[C:4]([C:17]([O:19][CH3:20])=[O:18])[C:3]=1[CH3:21].[C:22]1(B(O)O)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(=O)([O-])[O-].[Na+].[Na+].O>COCCOC.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>[F:16][C:13]1[CH:14]=[CH:15][C:10]([S:7]([N:6]2[C:2]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[C:3]([CH3:21])[C:4]([C:17]([O:19][CH3:20])=[O:18])=[CH:5]2)(=[O:9])=[O:8])=[CH:11][CH:12]=1
Reactant: COC(=O)c1cn(S(=O)(=O)c2ccc(F)cc2)c(Br)c1C
Reactant: OB(O)c1ccccc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: COCCOC
Product: COC(=O)c1cn(S(=O)(=O)c2ccc(F)cc2)c(-c2ccccc2)c1C
Temperature: 70 °C
Reaction time: 12 h
Yield: 84 %

Procedure:
Under an argon atmosphere, a suspension of methyl 5-bromo-1-[(4-fluorophenyl)sulfonyl]-4-methyl-1H-pyrrole-3-carboxylate (2.10 g), phenylboronic acid (1.42 g), tetrakis(triphenylphosphine)palladium (0.65 g), sodium carbonate (1.77 g) in 1,2-dimethoxyethane (11 mL)-water (11 mL) was stirred at 70° C. for 12 hr. After cooling, the reaction mixture was filtered through celite, and celite was washed with ethyl acetate. The organic layer was separated from the filtrate, washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=19:1→7:3) to give the title compound as a colorless oil (yield 1.75 g, 84%).
Reaction SMILES: C([O:4][C@@H:5]1[C@@H:9]([CH2:10][O:11]C(=O)C)[O:8][C@@H:7]([N:15]2[CH:22]=[CH:21][C:19](=[O:20])[NH:18][C:16]2=[O:17])[C@@H:6]1Br)(=O)C.C([SnH](CCCC)CCCC)CCC.C([Sn](Cl)(CCCC)CCCC)CCC.[BH4-].[Na+].N>C(O)C>[C@@H:7]1([N:15]2[CH:22]=[CH:21][C:19](=[O:20])[NH:18][C:16]2=[O:17])[O:8][C@H:9]([CH2:10][OH:11])[C@@H:5]([OH:4])[CH2:6]1
Reactant: CC(=O)OC[C@H]1O[C@@H](n2ccc(=O)[nH]c2=O)[C@H](Br)[C@@H]1OC(C)=O
Agent: CCCC[SnH](CCCC)CCCC
Agent: CCCC[Sn](Cl)(CCCC)CCCC
Agent: N
Solvent: CCO
Product: O=c1ccn([C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)[nH]1

Procedure:
For example, addition of excess acetyl bromide (3.2 eq) plus 30% HBr in acetic acid (1.2 eq) to uridine at 55°-60° C. gave the desired 3',5'-di-O-acetyl-2'-bromo-2'-deoxyuridine 2 (FIG. 1; X=O in uridine and uridine derivatives) in excellent yield (>95%). 3',4'-Di-O-acetyl-2'-bromo-2'-deoxyuridine 2 was then reduced to 3 by tributyltin hydride (provided either as the premade compound or prepared by in situ generation through the reaction of tributyltin chloride with sodium borohydride) in absolute ethanol in excellent yield (>95%). 2',3'-Di-O-acetyl-2'-deoxyuridine was treated with methanolic ammonia to obtain an excellent yield of 2'-deoxyuridine. The overall yield of this process was 72-76% without chromatography.
Reaction SMILES: [N:1]1([C:7]([C:9]2[C:10]3[CH2:27][S:26](=[O:29])(=[O:28])[C:25]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[C:11]=3[N:12]([CH:14]3[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]3)[N:13]=2)=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C(N(CC)CC)C.[CH3:37][S:38](Cl)(=[O:40])=[O:39].O>C1COCC1>[CH3:37][S:38]([N:17]1[CH2:18][CH2:19][CH:14]([N:12]2[C:11]3[C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][C:25]=4[S:26](=[O:29])(=[O:28])[CH2:27][C:10]=3[C:9]([C:7]([N:1]3[CH2:2][CH2:3][O:4][CH2:5][CH2:6]3)=[O:8])=[N:13]2)[CH2:15][CH2:16]1)(=[O:40])=[O:39]
Reactant: CS(=O)(=O)Cl
Reactant: O=C(c1nn(C2CCNCC2)c2c1CS(=O)(=O)c1ccccc1-2)N1CCOCC1
Solvent: CCN(CC)CC
Solvent: O
Solvent: C1CCOC1
Product: CS(=O)(=O)N1CCC(n2nc(C(=O)N3CCOCC3)c3c2-c2ccccc2S(=O)(=O)C3)CC1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To a solution of 3-(morpholin-4-ylcarbonyl)-1-piperidin-4-yl-1,4-dihydrothiochromeno[4,3-c]pyrazole 5,5-dioxide (30 mg, 0.066 mmol) in THF (10 mL) is added triethylamine (40 □l, 0.26 mmol) and the reaction mass is cooled to 0° C. after which methane sulfonyl chloride (0.01 mL, 0.099 mmol) is slowly added. The reaction mixture is slowly warmed to RT then stirred for 12 h. After this time, water is added to the reaction mixture that is then extracted with EtOAc. The organic layer is separated, dried under sodium sulphate and concentrated under reduced pressure. Compound is then purified by neutral alumina column chromatography (0.2% MeOH in chloroform) to afford the title compound as an off white solid. 1H NMR (DMSO-d6, 400 MHz): δ 8.20-8.18 (d, J=7.0 Hz, 1H), 7.78-7.75 (m, 1H), 7.67-7.64 (m, 1H), 7.52-7.49 (m, 1H), 4.70 (m, 3H), 4.18 (m, 2H), 4.05 (m, 2H), 3.81 (s, 6H), 2.99-2.94 (t, J=11.4 Hz, 2H), 2.80 (s, 3H), 2.47-2.42 (m, 2H), 2.24-2.18 (m, 2H). MS (ESI+): 495.0. HPLC (max plot) 93.19%; Rt 3.18 min.
Reaction SMILES: C([N:4]1[C:12]2[C:7](=[CH:8][C:9]([C:13]3[NH:14][C:15]4[N:16]([N:20]=[C:21]([CH2:23][CH3:24])[N:22]=4)[C:17](=[O:19])[CH:18]=3)=[CH:10][CH:11]=2)[CH:6]=[N:5]1)(=O)C.C(=O)([O-])[O-].[K+].[K+].O>CO>[CH2:23]([C:21]1[N:22]=[C:15]2[NH:14][C:13]([C:9]3[CH:8]=[C:7]4[C:12](=[CH:11][CH:10]=3)[NH:4][N:5]=[CH:6]4)=[CH:18][C:17](=[O:19])[N:16]2[N:20]=1)[CH3:24]
Reactant: CCc1nc2[nH]c(-c3ccc4c(cnn4C(C)=O)c3)cc(=O)n2n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CO
Product: CCc1nc2[nH]c(-c3ccc4[nH]ncc4c3)cc(=O)n2n1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 5-(1-acetyl-1H-indazol-5-yl)-2-ethyl-[1,2,4]triazolo[1,5-α]pyrimidin-7(4H)-one (130 mg, crude) in methanol (5 ml) was added potassium carbonate (20 mg, 0.14 mmol) and water (1 ml), and the reaction mixture was stirred overnight at room temperature. The reaction mixture was concentrated under vacuum and diluted with water (10 ml). The product was collected by filtration and washed with ethanol (10 ml) to afford 2-ethyl-5-(1H-indazol-5-yl)-[1,2,4]triazolo[1,5-α]pyrimidin-7(4H)-one as a yellow solid (66 mg, 18% 2 steps).
Reaction SMILES: [CH3:1][C:2]1[O:3][C:4]2[C:11](Br)=[CH:10][CH:9]=[CH:8][C:5]=2[C:6]=1[CH3:7].[C:13]1(C)C=CC=C[CH:14]=1.C(C([SnH3])=C(CCCC)CCCC)CCC.[OH-].[Na+]>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.C(OCC)(=O)C>[CH3:1][C:2]1[O:3][C:4]2[C:11]([CH:13]=[CH2:14])=[CH:10][CH:9]=[CH:8][C:5]=2[C:6]=1[CH3:7]
Reactant: Cc1oc2c(Br)cccc2c1C
Reactant: Cc1ccccc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: CCCCC([SnH3])=C(CCCC)CCCC
Agent: [Na+]
Solvent: CCOC(C)=O
Product: C=Cc1cccc2c(C)c(C)oc12
Reaction time: 2 h

Procedure:
32 g (142 mmol) of 2,3-dimethyl-7-bromobenzofuran, 3.3 g (2.84 mmol) of tetrakis(triphenylphosphine)palladium, 300 ml of toluene and 50 g (156.2 mmol) of tributylvinylstannane are introduced into a 1 l three-necked flask equipped with a reflux condenser. The mixture is heated at reflux for 3 hours, 1 g of tetrakis(triphenylphosphine)palladium is added and heating is continued for 2 hours. The reaction mixture is allowed to return to room temperature and then 500 ml of ethyl acetate and 500 ml of aqueous sodium hydroxide solution are added. The organic phase is washed with brine, dried over magnesium sulphate and concentrated. The residue is distilled under a vacuum of 0.03 mm of Hg. The fraction distilling between 60 and 78° C. is collected and is subsequently purified by silica column chromatography (elution solvent: 1% ethyl acetate in cyclohexane). 13.5 g of 2,3-dimethyl-7-ethenylbenzofuran are obtained in the form of a colourless oil.
Reaction SMILES: [CH3:1][O-:2].[Na+].Cl[CH2:5][C:6]1[C:11]([CH3:12])=[C:10]([S:13][CH2:14][CH2:15][CH2:16][S:17][C:18]2[CH:19]=[CH:20][C:21]3[N:22]([C:24]([N+:27]([O-:29])=[O:28])=[CH:25][N:26]=3)[N:23]=2)[CH:9]=[CH:8][N:7]=1>CO>[CH3:1][O:2][CH2:5][C:6]1[C:11]([CH3:12])=[C:10]([S:13][CH2:14][CH2:15][CH2:16][S:17][C:18]2[CH:19]=[CH:20][C:21]3[N:22]([C:24]([N+:27]([O-:29])=[O:28])=[CH:25][N:26]=3)[N:23]=2)[CH:9]=[CH:8][N:7]=1
Reactant: C[O-]
Reactant: Cc1c(SCCCSc2ccc3ncc([N+](=O)[O-])n3n2)ccnc1CCl
Agent: [Na+]
Solvent: CO
Product: COCc1nccc(SCCCSc2ccc3ncc([N+](=O)[O-])n3n2)c1C
Temperature: 25 °C

Procedure:
A solution of sodium methanolate (0.69 ml of a 30% strength solution) is added to a suspension of 6-[3-(2-chloromethyl-3-methylpyridin-4-ylsulfanyl)-propylsulfanyl]-3-nitroimidazo[1,2-b]pyridazine (1.23 g, 3 mmol) in methanol (75 ml). After heating under reflux for 16 h and cooling to room temperature the solvent is evaporated in vacuo. The residue is chromatographed (silica, toluene/dioxane 5:1) and crystallized from diisopropylether/ethyl acetate to give the title compound as off-white crystals, 0.34 g (28 %). M.p. 107-110° C.