Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:25]=[CH:26][C:27]=1[Cl:28])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([C@H:13]2[O:18][C:17]3[CH:19]=[CH:20][C:21]([CH:23]=O)=[CH:22][C:16]=3[O:15][CH2:14]2)=[CH:9][CH:8]=1.C1CCN2C(=NCCC2)CC1.[CH3:40][C:41]([O:44][C:45]([NH:47][CH:48](P(OC)(OC)=O)[C:49]([O:51][CH3:52])=[O:50])=[O:46])([CH3:43])[CH3:42]>C(Cl)Cl>[CH3:52][O:51][C:49](=[O:50])[C:48]([NH:47][C:45]([O:44][C:41]([CH3:40])([CH3:42])[CH3:43])=[O:46])=[CH:23][C:21]1[CH:20]=[CH:19][C:17]2[O:18][C@H:13]([C:10]3[CH:9]=[CH:8][C:7]([O:6][CH2:5][C:4]4[CH:25]=[CH:26][C:27]([Cl:28])=[C:2]([Cl:1])[CH:3]=4)=[CH:12][CH:11]=3)[CH2:14][O:15][C:16]=2[CH:22]=1
Reactant: O=Cc1ccc2c(c1)OC[C@@H](c1ccc(OCc3ccc(Cl)c(Cl)c3)cc1)O2
Reactant: COC(=O)C(NC(=O)OC(C)(C)C)P(=O)(OC)OC
Solvent: ClCCl
Solvent: C1CCC2=NCCCN2CC1
Product: COC(=O)C(=Cc1ccc2c(c1)OC[C@@H](c1ccc(OCc3ccc(Cl)c(Cl)c3)cc1)O2)NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 14 h

Procedure:
(R)-2-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2,3-dihydro-benzo[1,4]dioxine-6-carbaldehyde (5.0 g) was dissolved in 25 mL dry DCM under nitrogen at rt and 3.6 mL DBU was added by syringe. 3.8 g of Boc-phosphonoglycine trimethyl ester in 10 mL dry DCM was added by syringe dropwise and the mixture stirred at rt for 14 hours. The residue was purified over silica (hexanes to 8:2 hexanes/EtOAc) 4.9 g desired product after drying under vacuum. 1H NMR (400 MHz, CDCl3): 7.54 (d, 1H), 7.46 (d, 1H), 7.35 (m, 2H), 7.27 (m, 1H), 7.22-7.19 (m, 2H), 7.11 (m, 1H), 6.98 (m, 2H), 6.93 (d, 1H), 5.10 (m, 1H), 5.04 (s, 2H), 4.32 (m, 1H), 4.02 (m, 1H), 3.84 (s, 3H), 1.44 (s, 9H).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH:10]=[CH:11][C:12]2[CH:22]=[CH:21][CH:20]=[CH:19][C:13]=2/[C:14](/[NH:17]O)=[N:15]\[H])=[N:2]1.[C:23]([O:27][CH3:28])(=[O:26])[C:24]#[CH:25].O>CO>[CH3:28][O:27][C:23]([C:24]1[NH:15][C:14]([C:13]2[CH:19]=[CH:20][CH:21]=[CH:22][C:12]=2/[CH:11]=[CH:10]/[C:3]2[C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[NH:1][N:2]=2)=[N:17][CH:25]=1)=[O:26]
Reactant: C#CC(=O)OC
Reactant: [H]/N=C(/NO)c1ccccc1C=Cc1n[nH]c2ccccc12
Solvent: CO
Solvent: O
Product: COC(=O)c1cnc(-c2ccccc2/C=C/c2n[nH]c3ccccc23)[nH]1
Yield: 4.5 %

Procedure:
(E)-2-[2-(1H-indazol-3-yl)vinyl]-N-hydroxybenzamidine (0.30 g, 0.83 mmol) obtained in Step 1 of Example 175 was dissolved in methanol (8.0 mL) and after heating methyl propiolate (0.21 mL, 2.5 mmol) under reflux for 5 hours, water was added to stop the reaction. The mixture was extracted with ethyl acetate and the organic layer was concentrated. The residue was purified by preparative thin-layer chromatography (chloroform/acetone=4/1) to obtain Compound 195 (13 mg, 5%).
Reaction SMILES: [CH2:1]([C:13]1[CH:17]=[C:16]([CH:18]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:19]([OH:21])=O)[O:15][N:14]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].C(C1ON=C(C(C2C=CC=CC=2)C(O)=O)C=1)CCCCCCCCCCC.[F:55][C:56]1[CH:62]=[C:61]([F:63])[CH:60]=[CH:59][C:57]=1[NH2:58]>>[F:55][C:56]1[CH:62]=[C:61]([F:63])[CH:60]=[CH:59][C:57]=1[NH:58][C:19](=[O:21])[CH:18]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[O:15][N:14]=[C:13]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])[CH:17]=1
Reactant: CCCCCCCCCCCCc1cc(C(C(=O)O)c2ccccc2)on1
Reactant: Nc1ccc(F)cc1F
Agent: CCCCCCCCCCCCc1cc(C(C(=O)O)c2ccccc2)no1
Product: CCCCCCCCCCCCc1cc(C(C(=O)Nc2ccc(F)cc2F)c2ccccc2)on1

Procedure:
In a manner similar to Example 128, a mixture of 3-dodecyl-α-phenyl-5-isoxazole acetic acid and 5-dodecyl-α-phenyl-3-isoxazole acetic acid was condensed with 2,4-difluoroaniline to give, after chromatography, pure title compound; mp 68°-70° C.
Reaction SMILES: [O:1]=[C:2]1[C:10]2([C:22]3[C:13](=[CH:14][C:15]4[O:20][CH2:19][CH2:18][O:17][C:16]=4[CH:21]=3)[O:12][CH2:11]2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]1[CH2:23][C:24]1[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][CH:25]=1.[NH2:32][OH:33].N1[CH:39]=[CH:38]C=CC=1.C(OC(=O)C)(=O)C>CS(C)=O.O>[CH3:38][C:39]1[O:33][N:32]=[C:28]([C:27]2[CH:30]=[CH:31][C:24]([CH2:23][N:3]3[C:4]4[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=4)[C:10]4([C:22]5[C:13](=[CH:14][C:15]6[O:20][CH2:19][CH2:18][O:17][C:16]=6[CH:21]=5)[O:12][CH2:11]4)[C:2]3=[O:1])=[CH:25][CH:26]=2)[N:29]=1
Reactant: N#Cc1ccc(CN2C(=O)C3(COc4cc5c(cc43)OCCO5)c3ccccc32)cc1
Reactant: NO
Reactant: c1ccncc1
Solvent: CS(C)=O
Solvent: O
Solvent: CC(=O)OC(C)=O
Product: Cc1nc(-c2ccc(CN3C(=O)C4(COc5cc6c(cc54)OCCO6)c4ccccc43)cc2)no1
Temperature: 80 °C
Yield: 85 %

Procedure:
To a solution of 4-[(2′-oxo-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-1′(2′H)-yl)methyl]benzonitrile (0.41 g, 1.0 mmol) in dimethylsulfoxide (20 mL) was added hydroxylamine (50% w/w solution in water, 2.0 mL, 33 mmol). The mixture was heated at 80° C. for 16 h, allowed to cool to ambient temperature and diluted with water (50 mL), causing a precipitate to be deposited. The solid was collected by filtration and combined with pyridine (2.0 mL) and acetic anhydride (0.2 g, 2.0 mmol) in a 10 mL microwave reaction vessel. The mixture was heated at 170° C. for 15 min under microwave irradiation, allowed to cool to ambient temperature and concentrated in vacuo. The residue was purified by column chromatography and eluted with a 15% to 50% gradient of ethyl acetate in hexanes to afford 1′-[4-(5-methyl-1,2,4-oxadiazol-3-yl)benzyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.52 g, 85%) as a colorless solid: mp 174-175° C. (ethyl acetate/hexanes); 1H NMR (300 MHz, DMSO-d6) δ 8.06-8.00 (m, 2H), 7.42 (d, J=8.3 Hz, 2H), 7.22-7.13 (m, 2H), 7.04-6.97 (m, 1H), 6.75 (d, J=7.7 Hz, 1H), 6.50 (s, 1H), 6.23 (s, 1H), 5.12 (d, J=15.8 Hz, 1H), 4.94 (d, J=8.9 Hz, 1H), 4.85 (d, J=15.8 Hz, 1H), 4.66 (d, J=8.9 Hz, 1H), 4.21-4.07 (m, 4H), 2.63 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ 177.6, 176.6, 168.0, 155.3, 144.7, 141.9, 138.4, 132.2, 128.9, 128.0, 127.8, 126.5, 124.0, 123.6, 120.9, 111.5, 109.2, 99.5, 80.1, 58.1, 43.9, 12.4; MS (ES+) m/z 467.9 (M+1).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[O:9][C:10]3[C:11]([N:16]=2)=[N:12][CH:13]=[CH:14][CH:15]=3)[CH:5]=[CH:6][CH:7]=1.[CH3:17][N:18]([CH2:20][CH:21]=O)[CH3:19].C(OC(OCC)CN(C)C)C.[BH4-].[Na+]>O.C(O)C>[CH3:17][N:18]([CH3:19])[CH2:20][CH2:21][NH:1][C:2]1[CH:3]=[C:4]([C:8]2[O:9][C:10]3[C:11]([N:16]=2)=[N:12][CH:13]=[CH:14][CH:15]=3)[CH:5]=[CH:6][CH:7]=1
Reactant: Nc1cccc(-c2nc3ncccc3o2)c1
Reactant: CN(C)CC=O
Agent: CCOC(CN(C)C)OCC
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: CN(C)CCNc1cccc(-c2nc3ncccc3o2)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 1.1 g., (0.005 mole) of 2-(3-aminophenyl)oxazolo[4,5-b]pyridine and 50 ml. of ethanol is reacted with dimethylaminoacetaldehyde [from 0.96 g. (0.006 mole) dimethylaminoacetaldehyde diethylacetal]by gentle heating to complete the intermediate Schiff base formation. The mixture is then cooled and 60 mg., (0.0015 mole) of sodium borohydride is added, and the mixture allowed to stir overnight at room temperature. Water is added, the solvents are removed in vacuo, and the residue is distributed between water and methylene chloride. The organic layer is dried and concentrated in vacuo to give crude 2-[3-(2-dimethylaminoethyl)aminophenyl]oxazolo[4,5-b]pyridine, purified via column chromatography using an alumina column with an ethylacetate-ether mixture (v/v 0-60% ethylacetate) as eluant.
Reaction SMILES: [N-:1]=[N+:2]=[N-:3].[Na+].[CH2:5]([O:7][C:8]([C@:10]1([N:30]=[N+:31]=[N-:32])[C@@H:15](OS(C(F)(F)F)(=O)=O)[CH2:14][C@@H:13]2[C@H:11]1[C@@:12]2([F:29])[C:24]([O:26][CH2:27][CH3:28])=[O:25])=[O:9])[CH3:6].C(OCC)C>CN(C)C=O>[CH2:5]([O:7][C:8]([C@:10]1([N:30]=[N+:31]=[N-:32])[C@H:15]([N:1]=[N+:2]=[N-:3])[CH2:14][C@@H:13]2[C@H:11]1[C@@:12]2([F:29])[C:24]([O:26][CH2:27][CH3:28])=[O:25])=[O:9])[CH3:6]
Reactant: CCOC(=O)[C@@]1(F)[C@@H]2C[C@H](OS(=O)(=O)C(F)(F)F)[C@@](N=[N+]=[N-])(C(=O)OCC)[C@@H]21
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CCOCC
Solvent: CN(C)C=O
Product: CCOC(=O)[C@@]1(F)[C@@H]2C[C@@H](N=[N+]=[N-])[C@@](N=[N+]=[N-])(C(=O)OCC)[C@@H]21
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 93 %

Procedure:
56 mg of sodium azide was added to 250 mg of (1R,2R,3S,5R,6R)-2-azido-6-fluoro-3-trifluoromethanesulfonyloxy-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid diethyl ester dissolved in 5 mL of N,N-dimethylformamide, and the mixture was stirred for 30 minutes at room temperature. After 100 mL of diethyl ether was added to the reaction solution, this ether solution was washed four times with water and then dried over anhydrous sodium sulfate. The desiccant was filtered off, and the filtrate was concentrated under reduced pressure The residue was purified by column chromatography (silica gel: Wako gel C200 (made by Wako Pure Chemical Industries Ltd.), eluent: hexane-ethyl acetate=10:1), thereby yielding 175 mg of (1R,2R,3R,5R,6R)-2,3-diazido-6-fluoro-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid diethyl ester.
Reaction SMILES: [Si:1]([O:8][CH2:9][C@@H:10]1[CH2:14][CH2:13][C@H:12]([CH2:15][O:16][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18])[N:11]1[C:24]1[N:29]=[C:28]([C:30]2[CH:35]=[CH:34][C:33]([N+:36]([O-])=O)=[CH:32][CH:31]=2)[N:27]=[C:26]([N:39]2[CH2:45][CH:44]3[O:46][CH:41]([CH2:42][CH2:43]3)[CH2:40]2)[N:25]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H][H]>[Pd].O1CCCC1>[CH:41]12[O:46][CH:44]([CH2:43][CH2:42]1)[CH2:45][N:39]([C:26]1[N:25]=[C:24]([N:11]3[C@@H:12]([CH2:15][O:16][Si:17]([C:20]([CH3:22])([CH3:23])[CH3:21])([CH3:19])[CH3:18])[CH2:13][CH2:14][C@H:10]3[CH2:9][O:8][Si:1]([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:3])[CH3:2])[N:29]=[C:28]([C:30]3[CH:35]=[CH:34][C:33]([NH2:36])=[CH:32][CH:31]=3)[N:27]=1)[CH2:40]2
Reactant: [H][H]
Reactant: CC(C)(C)[Si](C)(C)OC[C@H]1CC[C@@H](CO[Si](C)(C)C(C)(C)C)N1c1nc(-c2ccc([N+](=O)[O-])cc2)nc(N2CC3CCC(C2)O3)n1
Agent: [Pd]
Solvent: C1CCOC1
Product: CC(C)(C)[Si](C)(C)OC[C@H]1CC[C@@H](CO[Si](C)(C)C(C)(C)C)N1c1nc(-c2ccc(N)cc2)nc(N2CC3CCC(C2)O3)n1

Procedure:
A suspension of palladium on charcoal (10%, 100 mg) and crude 3-(4-((2S,5R)-2,5-bis((tert-butyldimethylsilyloxy)methyl)pyrrolidin-1-yl)-6-(4-nitrophenyl)-1,3,5-triazin-2-yl)-8-oxa-3-azabicyclo[3.2.1]octane (3.4 mmol maximum) in tetrahydrofuran (30 mL) was shaken for 8 hours under 50 psi of hydrogen. The mixture was filtered through a pad of Celite™ diatomaceous earth and concentrated under reduced pressure to provide the title compound as an orange foam. MS (ES+)=642.4 (M+H)+
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N:14]2[CH2:18][C@H:17]([CH2:19]S(C)(=O)=O)[O:16][C:15]2=[O:24])[CH:5]=[CH:6][C:7]=1[N:8]1[CH:12]=[C:11]([CH3:13])[N:10]=[N:9]1.[N-:25]=[N+:26]=[N-:27].[Na+]>CN(C=O)C>[N:25]([CH2:19][C@@H:17]1[O:16][C:15](=[O:24])[N:14]([C:4]2[CH:5]=[CH:6][C:7]([N:8]3[CH:12]=[C:11]([CH3:13])[N:10]=[N:9]3)=[C:2]([F:1])[CH:3]=2)[CH2:18]1)=[N+:26]=[N-:27]
Reactant: Cc1cn(-c2ccc(N3C[C@H](CS(C)(=O)=O)OC3=O)cc2F)nn1
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1cn(-c2ccc(N3C[C@H](CN=[N+]=[N-])OC3=O)cc2F)nn1
Temperature: 70 °C
Reaction time: 1 h
Yield: 95.7 %

Procedure:
(5R)-3-[3-Fluoro-4-(4-methyl-1,2,3-triazol-1-yl)phenyl]-5-[(methanesulfonyl)methyl]-oxazolidin 2-one (Intermediate 18) (5.0 g, 13.5 mmol) was dissolved in DMF (45 ml). Sodium azide (1.75 g, 27.0 mmol) was added and the reaction mixture was stirred at 70° C. for one hour. It was partitioned between ethyl acetate and saturated sodium bicarbonate, the organic phase was washed with water and brine, dried over magnesium sulfate and concentrated under reduced pressure to give the product as a white solid (4.1 g), which was used without further purification.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[C:16]([F:24])[CH:15]=3)[CH:11]=[C:10]([C:25]([F:28])([F:27])[F:26])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[NH2:29][C:30]1[CH:35]=[CH:34][C:33](B2OC(C)(C)C(C)(C)O2)=[CH:32][N:31]=1>>[F:24][C:16]1[CH:15]=[C:14]([C:12]2[CH:11]=[C:10]([C:25]([F:28])([F:27])[F:26])[N:9]=[C:8]([C:4]3[CH:3]=[C:2]([C:33]4[CH:34]=[CH:35][C:30]([NH2:29])=[N:31][CH:32]=4)[CH:7]=[CH:6][CH:5]=3)[N:13]=2)[CH:19]=[CH:18][C:17]=1[C:20]([F:23])([F:22])[F:21]
Reactant: Fc1cc(-c2cc(C(F)(F)F)nc(-c3cccc(Br)c3)n2)ccc1C(F)(F)F
Reactant: CC1(C)OB(c2ccc(N)nc2)OC1(C)C
Product: Nc1ccc(-c2cccc(-c3nc(-c4ccc(C(F)(F)F)c(F)c4)cc(C(F)(F)F)n3)c2)cn1

Procedure:
The title compound was prepared from 2-(3-bromo-phenyl)-4-(3-fluoro-4-trifluoromethyl-phenyl)-6-trifluoromethyl-pyrimidine (example E.36) (0.23 g, 0.5 mmol) and commercially available 2-amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.14 g, 0.65 mmol) according to the general procedure VI. Obtained as a light yellow solid (0.19 g, 79%). MS (ISP) 479.0 [(M+H)+]; mp 212° C.
Reaction SMILES: [OH-:1].[K+].[F:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][C:8](=[O:13])[C:7]2=O.O1CCO[CH2:17][CH:16]1[CH2:21][CH2:22]O>O>[F:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]=[C:21]1[C:22]3[CH:6]=[CH:5][C:4]([C:12]4[CH:11]=[CH:10][CH:22]=[CH:21][C:16]=4[CH3:17])=[CH:17][C:16]=3[CH2:21][CH2:22][CH2:17][C:16]1=[C:7]2[C:8]([OH:13])=[O:1]
Reactant: [OH-]
Reactant: O=C1Nc2ccc(F)cc2C1=O
Reactant: OCCC1COCCO1
Agent: [K+]
Solvent: O
Product: Cc1ccccc1-c1ccc2c(c1)CCCc1c-2nc2ccc(F)cc2c1C(=O)O
Yield: 48 %

Procedure:
Potassium hydroxide (790 mg, 12.0 mmol) was dissolved in 3 ml of water, and 400 mg (2.40 mmol) of 5-fluoroisatin was added thereto. To this was added 600 mg (2.40 mmol) of compound s obtained in Reference Example 19 which was dissolved in dioxane-ethanol (2 ml-4 ml). The mixture was heat-refluxed for 6 days. The solvent was distilled off, and the residue was dissolved in water and washed with ether. The aqueous layer was filtered through Celite, and acetic acid was added to the flitrate. The precipitated crystals were collected by filtration. These crystals were then dried under reduced pressure, and recrystallized from dimethylformamide-water to obtain 460 mg of the above-mentioned compound (yield 48%).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[N:4][C:5]([O:8][C:9]2[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][C:10]=2[Cl:16])=[N:6][CH:7]=1.[N+:17]([C:20]1[CH:30]=[CH:29][CH:28]=[CH:27][C:21]=1[C:22]([N:24]=[C:25]=[O:26])=[O:23])([O-:19])=[O:18].O.CO>O1CCOCC1>[N+:17]([C:20]1[CH:30]=[CH:29][CH:28]=[CH:27][C:21]=1[C:22]([NH:24][C:25]([NH:13][C:12]1[CH:14]=[CH:15][C:9]([O:8][C:5]2[N:4]=[CH:3][C:2]([Br:1])=[CH:7][N:6]=2)=[C:10]([Cl:16])[CH:11]=1)=[O:26])=[O:23])([O-:19])=[O:18]
Reactant: Nc1ccc(Oc2ncc(Br)cn2)c(Cl)c1
Reactant: O=C=NC(=O)c1ccccc1[N+](=O)[O-]
Solvent: O
Solvent: CO
Solvent: C1COCCO1
Product: O=C(NC(=O)c1ccccc1[N+](=O)[O-])Nc1ccc(Oc2ncc(Br)cn2)c(Cl)c1
Yield: 84.5 %

Procedure:
Into a flask, a solution obtained by dissolving 6.80 g of the above 4-(5-bromo-2-pyrimidinyloxy)-3-chloroaniline in 30 ml of dioxane, was introduced, and a solution obtained by dissolving 5.76 g of 2-nitrobenzoylisocyanate in 30 ml of dioxane, was dropwise added thereto, and then the mixture was reacted at room temperature for 9 hours. After the completion of the reaction, the product was poured into water, subjected to filtration and washed with hot water. The crystals thereby obtained were put into methanol, and stirred, and then subjected to filtration again, to obtain 9.42 g of the desired product having a melting point of from 234 to 236° C.
Reaction SMILES: Br[CH2:2][C:3]1[CH:12]=[C:11]([N+:13]([O-:15])=[O:14])[CH:10]=[C:9]2[C:4]=1[N:5]=[C:6]([O:18][CH3:19])[C:7]([O:16][CH3:17])=[N:8]2.[NH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[P:27](=[O:34])([O:31][CH2:32][CH3:33])[O:28][CH2:29][CH3:30].C(N(C(C)C)CC)(C)C>C(#N)C>[CH3:17][O:16][C:7]1[C:6]([O:18][CH3:19])=[N:5][C:4]2[C:9](=[CH:10][C:11]([N+:13]([O-:15])=[O:14])=[CH:12][C:3]=2[CH2:2][NH:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[P:27](=[O:34])([O:28][CH2:29][CH3:30])[O:31][CH2:32][CH3:33])[N:8]=1
Reactant: COc1nc2cc([N+](=O)[O-])cc(CBr)c2nc1OC
Reactant: CCOP(=O)(OCC)c1ccccc1N
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: CCOP(=O)(OCC)c1ccccc1NCc1cc([N+](=O)[O-])cc2nc(OC)c(OC)nc12

Procedure:
190 mg (0.579 mmol) of 5-bromomethyl-7-nitro-2,3-dimethoxyquinoxaline, 159 mg (1.2 eq.) of diethyl 2-aminophenylphosphonate and 0.2 ml (2 eq.) of diisopropylethylamine are stirred at reflux for 20 hours in 8 ml of acetonitrile. The reaction mixture is evaporated and the residue is extracted with water and ethyl acetate. The combined organic phases are dried using brine and magnesium sulfate and evaporated. The title compound is obtained as a yellow solid.
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]([C:9]2[N:13]3[CH:14]=[CH:15][C:16]([C:19]([OH:22])([CH3:21])[CH3:20])=[C:17]([F:18])[C:12]3=[N:11][CH:10]=2)[CH:5]=[CH:6][C:7]=1[F:8].[O:23]1[C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=2[CH:25]=[C:24]1B(O)O>>[O:23]1[C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=2[CH:25]=[C:24]1[C:2]1[CH:3]=[C:4]([C:9]2[N:13]3[CH:14]=[CH:15][C:16]([C:19]([OH:22])([CH3:21])[CH3:20])=[C:17]([F:18])[C:12]3=[N:11][CH:10]=2)[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: CC(C)(O)c1ccn2c(-c3ccc(F)c(Cl)c3)cnc2c1F
Reactant: OB(O)c1cc2ccccc2o1
Product: CC(C)(O)c1ccn2c(-c3ccc(F)c(-c4cc5ccccc5o4)c3)cnc2c1F
Yield: 3 %

Procedure:
2-[3-(3-Chloro-4-fluorophenyl)-8-fluoroimidazo[1,2-α]pyridin-7-yl]-propan-2-ol and benzofuran-2-boronic acid were coupled in the same way as in Example 30 to give 2-{3-[3-(benzofuran-2-yl)-4-fluorophenyl]-8-fluoroimidazo[1,2-α]pyridin-7-yl}propan-2-ol as an off-white solid (6 mg, 3%): m/z (ES+) 405 [MH+].
Reaction SMILES: [CH3:1][C:2]([CH3:20])([O:4][C:5]([NH:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16]C(N)=O)=[CH:11][CH:10]=1)=[O:6])[CH3:3].FC(F)(F)C(OI(C1C=CC=CC=1)OC(=O)C(F)(F)F)=O.C(#[N:44])C>O>[CH3:1][C:2]([CH3:20])([O:4][C:5]([NH:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][NH2:44])=[CH:11][CH:10]=1)=[O:6])[CH3:3]
Reactant: CC#N
Reactant: CC(C)(C)OC(=O)NCc1ccc(CCC(N)=O)cc1
Agent: O=C(OI(OC(=O)C(F)(F)F)c1ccccc1)C(F)(F)F
Solvent: O
Product: CC(C)(C)OC(=O)NCc1ccc(CCN)cc1
Temperature: 40 °C
Reaction time: 8 h

Procedure:
A mixture of 10.0 g (38.1 mMol) of 4-[[[(1,1-dimethylethoxy)carbonyl]amino]methyl]benzenepropanamide, 18.5 g (43 mMol) of I,I-bis-(trifluoroacetoxy)iodobenzene, 100 ml of acetonitrile and 20 ml of water was stirred for 8 hours at a reaction temperature of 40° C. A further 2.5 g of I,I-bis-(trifluoroacetoxy)iodobenzene were added and the mixture was again kept at 40° C. for 6 hours. The acetonitrile was distilled off in vacuo, the residue was taken up in 200 ml of water, then filtered, the filtrate was extracted once with 50 ml of diethylether and then made alkaline with sodium hydroxide. The alkaline aqueous phase was extracted three times with 100 ml of dichloromethane, the combined dichloromethane extracts were dried over sodium sulphate and freed from solvent in vacuo. The residue was purified by column chromatograph on silica gel (Macherey-Nagel, 35-70 mesh ASTM) using first of all tert.butyl-methylether and then tert.butylmethylether/methanol/conc. aqueous ammonia=9/1/0.3 (v/v/v) as eluant. 4.5 g (50% of theory) of a colourless oil were obtained.
Reaction SMILES: CN(C)C=O.[F:6][C:7]1[C:8]([CH3:27])=[C:9]2[C:14](=[C:15]([F:18])[C:16]=1F)[N:13]([C@@H:19]1[CH2:21][C@@H:20]1[F:22])[CH:12]=[C:11]([C:23]([OH:25])=[O:24])[C:10]2=[O:26].Cl.Cl.[N:30]12[CH2:37][CH:34]([CH2:35][CH2:36]1)[NH:33][CH2:32][CH2:31]2>C(N(CC)CC)C>[N:30]12[CH2:37][CH:34]([CH2:35][CH2:36]1)[N:33]([C:16]1[C:15]([F:18])=[C:14]3[C:9]([C:10](=[O:26])[C:11]([C:23]([OH:25])=[O:24])=[CH:12][N:13]3[C@@H:19]3[CH2:21][C@@H:20]3[F:22])=[C:8]([CH3:27])[C:7]=1[F:6])[CH2:32][CH2:31]2
Reactant: Cc1c(F)c(F)c(F)c2c1c(=O)c(C(=O)O)cn2[C@@H]1C[C@@H]1F
Reactant: C1CN2CCC(C2)N1
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: Cc1c(F)c(N2CCN3CCC2C3)c(F)c2c1c(=O)c(C(=O)O)cn2[C@@H]1C[C@@H]1F
Temperature: 100 °C
Reaction time: 1 h
Yield: 62.3 %

Procedure:
To 5 ml of dried N,N-dimethylformamide were added 211 mg of 6,7,8-trifluoro-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-5-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, 372 mg of 1,4-diazabicyclo[3.2.1]octane dihydrochloride, and 2 ml of triethylamine, and the mixture was stirred at 100° C. for 1 hour. After allowing to cool, the reaction mixture was concentrated under reduced pressure, and the residue was dissolved in a 1N sodium hydroxide aqueous solution while cooling with ice. After neutralizing with 1N hydrochloric acid, the mixture was extracted with chloroform, and the extract was dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the resulting crude crystals were recrystallized from a mixed solvent of ethanol and 28% aqueous ammonia. The precipitated crystals were collected by filtration, washed with diethyl ether, and dried at 60° C. in vacuo overnight to yield 170 mg of the titled compound as a yellow powder.
Reaction SMILES: [CH3:1][C:2]1[S:3][C:4]2[C:10](=O)[C:9](=[CH:12]N3CCOCC3)[CH2:8][CH2:7][C:5]=2[N:6]=1.[N+]([O-])(O)=O.[OH:23][C:24]1[CH:25]=[C:26]([NH:30][C:31]([NH2:33])=[NH:32])[CH:27]=[CH:28][CH:29]=1.[OH-].[Na+]>COCCO>[CH3:1][C:2]1[S:3][C:4]2[C:10]3[N:33]=[C:31]([NH:30][C:26]4[CH:25]=[C:24]([OH:23])[CH:29]=[CH:28][CH:27]=4)[N:32]=[CH:12][C:9]=3[CH2:8][CH2:7][C:5]=2[N:6]=1
Reactant: N=C(N)Nc1cccc(O)c1
Reactant: Cc1nc2c(s1)C(=O)C(=CN1CCOCC1)CC2
Agent: [Na+]
Agent: [OH-]
Solvent: COCCO
Solvent: O=[N+]([O-])O
Product: Cc1nc2c(s1)-c1nc(Nc3cccc(O)c3)ncc1CC2
Yield: 0.8 %

Procedure:
A mixture of 2-methyl-6-morpholin-4-ylmethylene-5,6-dihydro-4H-benzothiazol-7-one (210 mg, 7.94 mmol), N-(3-hydroxy-phenyl)-guanidine nitrate (170 mg, 7.94 mmol), NaOH (32 mg, 7.94 mmol), and 2-methoxyethanol (2 mL) was heated under reflux for 16 h. The reaction mixture was concentrated under vacuum. Flash column chromatography (10% MeOH:EtOAc) gave the pure title product as a yellow solid (20 mg, 8%): mp 310° C. (dec). Anal. RP-HPLC: tR 10.3 min (0-60% MeCN, purity 92%). 1H-NMR (DMSO-d6): δ 9.50 (s, 1H, OH/NH), 9.28 (s, 1H, OH/NH), 8.38 (s, 1H, Py-H), 7.37 (t, 1H, J 2.3, Ph-H), 7.27 (ddd, 1H, J 8.3, 2.3, 0.7, Ph-H), 7.08 (t, 1H, J 8.3, Ph-H), 6.40 (ddd, 1H, J 8.3, 2.3, 0.7, Ph-H), 3.05 (m, 4H, CH2—CH2), 2.78 (s, 3H, CH3). 13C-NMR (DMSO-d6): δ 168.71, 159.05, 158.88, 157.42, 155.97, 155.20, 141.75, 128.81, 127.83, 115.89, 109.69, 108.35, 105.87, 24.72, 23.09, 19.38. MS (ESI+): m/z 311.06 (M+H)+.
Reaction SMILES: [CH:1]1C=C(Cl)C=C(C(OO)=O)C=1.[I:12][C:13]1[CH:14]=[C:15]([C:19]2[N:20]=[CH:21][N:22]([CH3:35])[C:23]=2[C:24]2[S:34][C:27]3[N:28]=[CH:29][N:30]=[C:31](SC)[C:26]=3[CH:25]=2)[CH:16]=[CH:17][CH:18]=1.[S:36](S([O-])=O)([O-:39])(=O)=[O:37].[Na+].[Na+]>C(Cl)Cl>[I:12][C:13]1[CH:14]=[C:15]([C:19]2[N:20]=[CH:21][N:22]([CH3:35])[C:23]=2[C:24]2[S:34][C:27]3[N:28]=[CH:29][N:30]=[C:31]([S:36]([CH3:1])(=[O:39])=[O:37])[C:26]=3[CH:25]=2)[CH:16]=[CH:17][CH:18]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: O=S([O-])S(=O)(=O)[O-]
Reactant: CSc1ncnc2sc(-c3c(-c4cccc(I)c4)ncn3C)cc12
Agent: [Na+]
Solvent: ClCCl
Product: Cn1cnc(-c2cccc(I)c2)c1-c1cc2c(S(C)(=O)=O)ncnc2s1
Reaction time: 24 h
Yield: 68 %

Procedure:
m-CPBA (70-75%, 399 mg) was added to a solution of 6-[4-(3-iodophenyl)-1-methyl-1H-imidazol-5-yl]-4-(methylthio)thieno[2,3-d]pyrimidine (300 mg) in DCM (20 mL) and stirred for 24 hours. Aqueous sodium metabisulfite was added and the mixture extracted with DCM. The organic phase was washed with saturated aqueous NaHCO3, dried (MgSO4), filtered and concentrated in vacuo to give the title compound as a yellow solid (220 mg, 68%);