Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[CH3:2][N:3]1[CH2:9][CH2:8][C:7]2[CH:10]=[C:11]([O:18]C)[C:12]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:13][C:6]=2[CH2:5][CH2:4]1.[BrH:20]>>[BrH:20].[OH:18][C:11]1[C:12]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:13][C:6]2[CH2:5][CH2:4][N:3]([CH3:2])[CH2:9][CH2:8][C:7]=2[CH:10]=1
Reactant: COc1cc2c(cc1S(C)(=O)=O)CCN(C)CC2
Agent: Br
Agent: Cl
Product: CN1CCc2cc(O)c(S(C)(=O)=O)cc2CC1

Procedure:
Following the procedure of Example 4, 3-methyl-8-methoxy-7-methylsulfonyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride was reacted with 48% hydrobromic acid to give 8-hydroxy-3-methyl-7-methylsulfonyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide, m.p. 310° (decomp.).
Reaction SMILES: [C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[H-].[Na+].CS(O[CH2:19][CH:20]([CH2:26][CH:27]=[CH2:28])[CH2:21][CH2:22][CH2:23][C:24]#[N:25])(=O)=O.C(O)(=O)C>O1CCCC1>[C:24]([CH2:23][CH2:22][CH2:21][CH:20]([CH2:26][CH:27]=[CH2:28])[CH2:19][CH:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])[C:1]([O:9][CH2:10][CH3:11])=[O:8])#[N:25]
Reactant: C=CCC(CCCC#N)COS(C)(=O)=O
Reactant: CCOC(=O)CC(=O)OCC
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CC(=O)O
Product: C=CCC(CCCC#N)CC(C(=O)OCC)C(=O)OCC
Reaction time: 0.5 h

Procedure:
A solution of 5410 g of diethyl malonate in 2000 ml of tetrahydrofuran is added to a mixture of 1351 g of 60% sodium hydride in mineral oil in 36 L of tetrahydrofuran over a period of 4 hours, keeping the temperature below 26°, and the mixture is stirred for 1/2 hour. A solution of 3705 g of 6-methanesulfonyloxy-5-(2-propenyl)-hexanenitrile in 200 ml tetrahydrofuran is added rapidly and the mixture is heated under reflux for 24 hours and allowed to cool overnight. The mixture is neutralized to pH 7 with glacial acetic acid (about 1 L) and evaporated to dryness. A solution of the residue in 30 L of ether is washed consecutively with water, saturated sodium bicarbonate solution, water and brine, and evaporated to dryness. The mineral oil is separated in a separatory funnel and the remaining product is washed three times with heptane, concentrated at 80°/0.01 mm Hg, and distilled at 150° to remove diethyl malonate and obtain crude diethyl [5-cyano-2-(2-propenyl)-pentyl]-malonate.
Reaction SMILES: Br[C:2]1[N:7]2[CH:8]=[C:9]([CH2:11][O:12][C:13]3[CH:22]=[CH:21][C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[N:14]=3)[N:10]=[C:6]2[C:5]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)=[N:4][CH:3]=1.[NH:29]1[C:33]([C:34]2[CH:39]=[CH:38][C:37](B(O)O)=[CH:36][CH:35]=2)=[N:32][N:31]=[N:30]1>>[NH:32]1[C:33]([C:34]2[CH:39]=[CH:38][C:37]([C:2]3[N:7]4[CH:8]=[C:9]([CH2:11][O:12][C:13]5[CH:22]=[CH:21][C:20]6[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=6)[N:14]=5)[N:10]=[C:6]4[C:5]([N:23]4[CH2:28][CH2:27][O:26][CH2:25][CH2:24]4)=[N:4][CH:3]=3)=[CH:36][CH:35]=2)=[N:29][N:30]=[N:31]1
Reactant: Brc1cnc(N2CCOCC2)c2nc(COc3ccc4ccccc4n3)cn12
Reactant: OB(O)c1ccc(-c2nnn[nH]2)cc1
Product: c1ccc2nc(OCc3cn4c(-c5ccc(-c6nnn[nH]6)cc5)cnc(N5CCOCC5)c4n3)ccc2c1

Procedure:
Compound 31b was subjected to Suzuki coupling reaction conditions with (4-(1H-tetrazol-5-yl)phenyl)boronic acid using the methods described in Example 1, Step G to obtain compound 31c. 1H-NMR (400 MHz, DMSO-d6) 8.26 (d, J=8.6 Hz, 1H), 8.21 (d, J=8.6 Hz, 2H), 8.17 (s, 1H), 7.88-7.93 (m, 3H), 7.80 (d, J=8.6 Hz, 1H), 7.65-7.71 (m, 1H), 7.55 (s, 1H), 7.45 (t, J=7.0 Hz, 1H), 7.06 (d, J=9.0 Hz, 1H), 5.58 (s, 2H), 4.21-4.28 (m, 4H), 3.75-3.80 (m, 4H). Mass Spectrum (LCMS, ESI pos.) Calcd. for C27H23N9O2: 506.2 (M+H). Found 506.2.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11]O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N1C=CN=C1.[I:37]I>ClCCl>[C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][I:37])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: II
Reactant: OCCCCCc1ccccc1
Agent: c1c[nH]cn1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: ICCCCCc1ccccc1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
A mixture of 5-phenyl-pentane-1-ol (1.0 gm, 6.089 mmol) in dichloromethane (20 ml), triphenyl phosphine (2.35 gm, 8.52 mmol), imidazole (0.58 gm, 8.52 mmol) and elemental iodine (2.16 gm, 8.52 mmol) was stirred at room temperature for 12 h and solvent was removed under reduced pressure. The crude mixture was taken up in ethyl acetate (30 ml), washed with water (20 ml) and then with brine (30 ml). The layers were separated, the organic layer was dried over anhydrous sodium sulfate and solvent was removed under reduced pressure. The crude product was purified on column chromatography using hexane as an eluent to yield an oily liquid, 750 mg. 1H NMR (CDCl3): δ 1.30-1.70 (m, 4H), 1.80 (m, 2H), 2.6 (t, 2H, J=7.2 Hz), 3.10 (t, 2H, J=7.8 Hz), 7.00-7.34 (m, 5H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH:7](O)[CH2:6][CH2:5]2.[Br:12][Si](C)(C)C>C(Cl)(Cl)Cl>[Br:12][CH:7]1[C:8]2[C:4](=[CH:3][C:2]([Br:1])=[CH:10][CH:9]=2)[CH2:5][CH2:6]1
Reactant: C[Si](C)(C)Br
Reactant: OC1CCc2cc(Br)ccc21
Solvent: ClC(Cl)Cl
Product: Brc1ccc2c(c1)CCC2Br
Temperature: 25 °C
Reaction time: 8 h

Procedure:
The compound obtained in Step A (70.19 mmol) is brought into solution in 420 ml of CHCl3, and bromotrimethylsilane (13.90 ml, 105.28 mmol, 1.5 eq.) is added at room temperature. The reaction mixture is stirred overnight at room temperature. The solvent and excess bromotrimethylsilane are removed by evaporation under reduced pressure. The oil is taken up in 150 ml of CHCl3, washed with 2×80 ml of water and 3×100 ml of saturated NaCl and dried over Na2SO4. The organic phase is then concentrated under reduced pressure to yield the title compound in the form of a brown oil.
Reaction SMILES: [F:1][C:2]1[C:3](F)=[C:4]2[O:9][CH2:8][CH:7]([CH3:10])[N:6]3[CH:11]=[C:12]([C:17]([OH:19])=[O:18])[C:13](=[O:16])[C:14]([CH:15]=1)=[C:5]23.[Br:21][C:22]1[CH:30]=[CH:29][CH:28]=[C:27]2[C:23]=1[CH2:24][NH:25][CH2:26]2.C1CCN2C(=NCCC2)CC1>CN(C=O)C>[Br:21][C:22]1[CH:30]=[CH:29][CH:28]=[C:27]2[C:23]=1[CH2:24][N:25]([C:3]1[C:2]([F:1])=[CH:15][C:14]3[C:13](=[O:16])[C:12]([C:17]([OH:19])=[O:18])=[CH:11][N:6]4[CH:7]([CH3:10])[CH2:8][O:9][C:4]=1[C:5]=34)[CH2:26]2
Reactant: Brc1cccc2c1CNC2
Reactant: CC1COc2c(F)c(F)cc3c(=O)c(C(=O)O)cn1c23
Solvent: C1CCC2=NCCCN2CC1
Solvent: CN(C)C=O
Product: CC1COc2c(N3Cc4cccc(Br)c4C3)c(F)cc3c(=O)c(C(=O)O)cn1c23
Yield: 44.4 %

Procedure:
142 mg of 9,10-difluoro-2,3-dihydro-3-methyl-7--oxo-7H-pyrido[1,2,3-de][1,4]-benzoxazine-6-carboxylic acid, 149 mg of 4-bromoisoindoline, 114 mg of DBU, and 1.5 ml of anhydrous DMF were processed in the same manner as in Example 20 to produce 103 mg of the target compound.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[NH:10][C:9]=2[C:17]([NH2:19])=[O:18])=[CH:4][CH:3]=1.[CH3:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][C:23]=1[N:32]=[C:33]=[O:34]>>[CH3:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][C:23]=1[NH:32][C:33](=[O:34])[NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[NH:10][C:9]=2[C:17]([NH2:19])=[O:18])=[CH:6][CH:7]=1
Reactant: NC(=O)c1[nH]c2ncccc2c1-c1ccc(N)cc1
Reactant: COc1ccc(C(F)(F)F)cc1N=C=O
Product: COc1ccc(C(F)(F)F)cc1NC(=O)Nc1ccc(-c2c(C(N)=O)[nH]c3ncccc23)cc1

Procedure:
50 mg of solid beige-coloured 3-{4-[3-(2-methoxy-5-trifluoromethylphenyl)-ureido]phenyl}-1H-pyrrolo[2,3-b]pyridine-2-carboxamide are prepared as described in Example 7 starting with 3-(4-aminophenyl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide and 2-methoxy-5-trifluoromethylphenyl isocyanate.
Reaction SMILES: [OH:1][CH:2]1[CH:7]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)[CH2:6][CH2:5][N:4]([C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])[CH2:3]1.[C:25]1(OB(O)O)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(N(CC)CC)C>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.ClCCl>[OH:1][CH:2]1[CH:7]([C:8]2[CH:9]=[CH:10][C:11]([O:14][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[CH:12][CH:13]=2)[CH2:6][CH2:5][N:4]([C:15]([O:17][CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[O:16])[CH2:3]1
Reactant: O=C(OCc1ccccc1)N1CCC(c2ccc(O)cc2)C(O)C1
Reactant: OB(O)Oc1ccccc1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(OCc1ccccc1)N1CCC(c2ccc(Oc3ccccc3)cc2)C(O)C1
Temperature: 25 °C
Reaction time: 28 h

Procedure:
A suspension of 0.200 g of benzyl 3-hydroxy-4-(4-hydroxyphenyl)piperidine-1-carboxylate, 0.0906 g of phenylboric acid, 0.113 g of copper(II) acetate, 0.309 g of triethylamine, 0.700 g of 3 angstrom molecular sieves (powder) and 6 ml of dichloromethane is stirred vigorously at room temperature for 28 hours. The reaction mixture is clarified by filtration and concentrated by evaporation. The title compound is obtained as a yellowish solid from the residue by means of flash chromatography (SiO2 60F). Rf=0.44 (1:1 EtOAc-heptane); Rt=5.03.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:8]=[CH:9][C:10]3[CH:11]([CH:21]4[CH2:27][CH:26]5[NH:28][CH:23]([CH2:24][CH2:25]5)[CH2:22]4)[C:12]4[C:17]([O:18][C:19]=3[CH:20]=2)=[CH:16][CH:15]=[CH:14][CH:13]=4)[CH:2]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.C[N+](C)(C)C.[O:47]1[CH:51]=[CH:50][C:49]([CH:52]=O)=[CH:48]1>C(Cl)CCl.C(Cl)Cl>[O:47]1[CH:51]=[CH:50][C:49]([CH2:52][N:28]2[CH:23]3[CH2:24][CH2:25][CH:26]2[CH2:27][CH:21]([CH:11]2[C:10]4[CH:9]=[CH:8][C:7]([C:3]5[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=5)=[CH:20][C:19]=4[O:18][C:17]4[C:12]2=[CH:13][CH:14]=[CH:15][CH:16]=4)[CH2:22]3)=[CH:48]1
Reactant: c1cncc(-c2ccc3c(c2)Oc2ccccc2C3C2CC3CCC(C2)N3)c1
Reactant: O=Cc1ccoc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: C[N+](C)(C)C
Solvent: ClCCl
Solvent: ClCCCl
Product: c1cncc(-c2ccc3c(c2)Oc2ccccc2C3C2CC3CCC(C2)N3Cc2ccoc2)c1
Temperature: 25 °C
Reaction time: 24 h
Yield: 75 %

Procedure:
To a solution of 3-(3-pyridin-3-yl-9H-xanthen-9-yl)-8-aza-bicyclo[3.2.1]octane, 3b (0.08 g, 0.134 mmol) in ClCH2CH2Cl (2 mL) was added tetramethyl-ammonium triacetoxyborohydride (0.053 g, 2.01 mmol) and 3-furaldehyde (0.17 mL, 2.0 mmol). The reaction was stirred at rt for 24 h. The reaction was diluted with CH2Cl2 (10 mL) and washed with 1 N NaOH. The organic phase was dried over sodium sulfate, filtered, and concentrated. The crude product was purified via reverse phase chromatography (eluent: CH3CN in H2O containing 0.1% TFA) to yield 0.045 g (75%) of title compound 8-furan-3-ylmethyl-3-(3-pyridin-3-yl-9H-xanthen-9-yl)-8-aza-bicyclo[3.2.1]-octane, 4b as a TFA salt. MS m/z=449.1 (MH+).
Reaction SMILES: [CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[CH2:11][C:12]([NH2:14])=[O:13])[CH:4]=[CH:3]1.C[O:16][C:17](=O)[C:18]([C:20]1[C:28]2[C:23](=[CH:24][C:25]([C:29]#[N:30])=[CH:26][CH:27]=2)[NH:22][CH:21]=1)=O.CC(C)([O-])C.[K+].C1COCC1>CN(C=O)C>[C:29]([C:25]1[CH:24]=[C:23]2[C:28]([C:20]([C:18]3[C:17](=[O:16])[NH:14][C:12](=[O:13])[C:11]=3[C:9]3[CH:8]=[CH:7][CH:6]=[C:5]4[C:10]=3[N:2]([CH3:1])[CH:3]=[CH:4]4)=[CH:21][NH:22]2)=[CH:27][CH:26]=1)#[N:30]
Reactant: Cn1ccc2cccc(CC(N)=O)c21
Reactant: COC(=O)C(=O)c1c[nH]c2cc(C#N)ccc12
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: Cn1ccc2cccc(C3=C(c4c[nH]c5cc(C#N)ccc45)C(=O)NC3=O)c21
Temperature: 70 °C

Procedure:
To a solution of 2-(1-methyl-1H-indol-7-yl)-acetamide (0.410 g, 2.18 mmol) and (6-cyano-1H-indol-3-yl)-oxo-acetic acid methyl ester (0.480 g, 2.10 mmol) in DMF (30 mL) under N2 was added a 1.0 M solution of potassium-tert-butoxide in THF (7.6 mL, 7.6 mmol) dropwise over 5 minutes. The mixture was heated at 70° C. for 17 h. The mixture was cooled to room temperature, quenched with 1N HCl (excess) and poured into EtOAc. The organic layer was separated, washed with water (3×), saturated aq NaHCO3, and brine, dried (MgSO4), filtered and concentrated onto flash SiO2. Flash chromatography (60–70% EtOAc/hex) gave the title compound as a bright orange-red solid which was dried under vacuum at 75° C. overnight (0.416 g, 54%). 1H NMR (400 MHz, DMSO-d6) 12.29 (br s, 1H), 11.26 (s, 1H), 8.03 (d, J=2.3 Hz, 1H), 7.86 (br s, 1H), 7.63 (d, J=8 Hz, 1H), 7.25 (d, J=3 Hz, 1H), 6.99 (dd, J=8, 8 Hz, 1H), 6.91 (d, J=8 Hz, 1H), 6.89 (d, J=8 Hz, 1H), 6.60 (d, J=8 Hz, 1H), 6.49 (d, J=3 Hz, 1H), 3.66 (s, 3H). IR (KBR, cm−1) 3282, 2223, 1751, 1698. MS (electrospray, m/z) 367.1 (M++1), 365.2 (M−−1). HRMS 367.1190 (M++1, calcd for C22H15N4O2 367.1195).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][CH:13]2[CH2:15][CH2:14]2)=[CH:4][N:3]=1.[F-:16].[Cs+]>CS(C)=O.O>[F:16][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][CH:13]2[CH2:15][CH2:14]2)=[CH:4][N:3]=1
Reactant: [F-]
Reactant: Clc1ncc(OC2CC2)c2ccccc12
Agent: [Cs+]
Solvent: O
Solvent: CS(C)=O
Product: Fc1ncc(OC2CC2)c2ccccc12
Temperature: 145 °C
Yield: 37.6 %

Procedure:
To a solution of 1-chloro-4-cyclopropoxyisoquinolin (2.3 g, 10.47 mmol) in DMSO (20 ml) was added cesium fluoride (6.36 g, 41.9 mmol) at room temperature. The reaction vessel (Pressure tube) was sealed and heated at 145° C. for 18 h. The reaction mass was diluted with water and extracted with ethyl acetate. The organic layer was dried over anhydrous Na2SO4 and evaporated under reduced pressure to get crude compound. The crude compound was purified by silica gel chromatography to get desired compound (0.8 g, 37.6%) as a white solid. 1H NMR (400 MHz, CDCl3): δ ppm 8.09-8.07 (m, 2H), 7.83 (s, 1H), 7.76-7.71 (m, 1H), 7.67-7.63 (m, 1H), 3.96-3.94 (m, 1H), 0.90-0.89 (m, 4H); 19F NMR: δ ppm −78.58 (1F); MS: MS m/z 204.2 (M++1).
Reaction SMILES: [C:1]1([N:7]2[C:19]3[CH:18]=[CH:17][C:16](B4OC(C)(C)C(C)(C)O4)=[CH:15][C:14]=3[C:13]3[C:8]2=[CH:9][CH:10]=[CH:11][CH:12]=3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Br:29][C:30]1[CH:35]=[CH:34][C:33](I)=[CH:32][CH:31]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.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>[Br:29][C:30]1[CH:35]=[CH:34][C:33]([C:16]2[CH:17]=[CH:18][C:19]3[N:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[C:8]4[C:13]([C:14]=3[CH:15]=2)=[CH:12][CH:11]=[CH:10][CH:9]=4)=[CH:32][CH:31]=1
Reactant: CC1(C)OB(c2ccc3c(c2)c2ccccc2n3-c2ccccc2)OC1(C)C
Reactant: Brc1ccc(I)cc1
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: [K+]
Solvent: O
Solvent: C1COCCO1
Product: Brc1ccc(-c2ccc3c(c2)c2ccccc2n3-c2ccccc2)cc1
Temperature: 100 °C
Yield: 44 %

Procedure:
A mixture of 9-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-carbazole (Compound 14) (5.0 g, 13.5 mmol), 4-bromoiodobenzene (10.76 g, 38 mmol), Pd(PPh3)4 (0.5 g, 0.43 mmol) and potassium carbonate (K2CO3)(5.52 g, 40 mmol) in dioxane/water (80 mL/15 mL) was degassed and heated at about 100° C. overnight, then worked up with ethyl acetate/brine. The organic phase was collected, dried over Na2SO4, and purified by flash column (hexanes to hexane/ethyl acetate 90:1). The main fraction was collected, concentrated, and a precipitate was filtered to give a white solid (Compound 15) (2.35 g, in 44% yield). Confirmed by LCMS (APCI): calculated for C24H17BrN (M+H): 398; Found: 398.
Reaction SMILES: [CH:1](=O)[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4].C([O-])(=O)C.[Na+].C(O)C.Cl.[NH2:19][C:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23]([OH:30])=[CH:22][CH:21]=1>O>[OH:4][C:3]1[CH:5]=[CH:6][CH:7]=[CH:8][C:2]=1[CH:1]=[N:19][C:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23]([OH:30])=[CH:22][CH:21]=1
Reactant: O=Cc1ccccc1O
Reactant: Nc1ccc(O)c2ccccc12
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: Oc1ccccc1C=Nc1ccc(O)c2ccccc12
Temperature: 50 °C
Reaction time: 0.25 h
Yield: 82.5 %

Procedure:
To a 500 milliliter round bottom flask equipped with a water condenser, magnetic stirrer and drying tube was added 5.50 grams (0.045 moles) of salicylaldehyde, 4.10 grams (0.050 moles) of sodium acetate and 40 milliliters of ethanol. The resulting mixture was then heated to a temperature of 50° C. and a solution consisting of 7.83 grams (0.040 moles) of 4-amino-1-naphthol hydrochloride in 20 milliliters of water was added thereto. The resulting reaction mixture was stirred for 15 minutes at a temperature of 50° C. and then cooled to room temperature forming a precipitate. The precipitate was removed from the reaction mixture by filtration, washed with water and dried over magnesium sulfate to give 8.68 grams (0.033 moles) of 4-(2-hydroxybenzylideneamino)-1-naphthol in the form of reddish-brown crystals having a melting point of 153.5°-157° C.
Reaction SMILES: [CH:1]1[C:15](=[O:16])[N:14]=[C:13]2[N:3]([C@@H:4]3[O:8][C@H:7]([CH2:9][OH:10])[C@@H:6]([OH:11])[C@@H:5]3[O:12]2)[CH:2]=1.FC(F)(F)C(O)=[O:20]>CN(C)C=O>[C@@H:4]1([N:3]2[CH:2]=[CH:1][C:15](=[O:16])[NH:14][C:13]2=[O:12])[O:8][C@H:7]([CH2:9][OH:10])[C@@H:6]([OH:11])[C@@H:5]1[OH:20]
Reactant: O=c1ccn2c(n1)O[C@H]1[C@H](O)[C@@H](CO)O[C@H]12
Reactant: O=C(O)C(F)(F)F
Solvent: CN(C)C=O
Product: O=c1ccn([C@@H]2O[C@H](CO)[C@@H](O)[C@@H]2O)c(=O)[nH]1
Temperature: 80 °C

Procedure:
500 mg (2.23 mmol) of the above product 2 is taken as the starting material to immerse in 5 mL of dimethyl formamide. 70 mL of trifluoroacetic acid (0.05N) is added with continuously stirring at 80° C. The solution is concentrated under reduced pressure by removing the residual part of the solution after the completion of the reaction, and then purified by rapid column chromatography (MeOH/CHCl3=1:3). A white powder product (1-(β-D-arabinofuranosyl)-pyrimidin-2,4(3H)-dione) 3 is obtained. Its weight and yield are 510 mg and 95% respectively.
Reaction SMILES: [Br:1][C:2]1[C:14]([OH:15])=[CH:13][C:5]2[C:6]([CH3:12])([CH3:11])[O:7][C:8](=[O:10])[NH:9][C:4]=2[CH:3]=1.[CH3:16][C:17]1[CH:22]=[CH:21][C:20]([S:23][CH2:24][CH2:25][CH2:26][CH2:27]Cl)=[CH:19][CH:18]=1>>[Br:1][C:2]1[C:14]([O:15][CH2:27][CH2:26][CH2:25][CH2:24][S:23][C:20]2[CH:19]=[CH:18][C:17]([CH3:16])=[CH:22][CH:21]=2)=[CH:13][C:5]2[C:6]([CH3:12])([CH3:11])[O:7][C:8](=[O:10])[NH:9][C:4]=2[CH:3]=1
Reactant: Cc1ccc(SCCCCCl)cc1
Reactant: CC1(C)OC(=O)Nc2cc(Br)c(O)cc21
Product: Cc1ccc(SCCCCOc2cc3c(cc2Br)NC(=O)OC3(C)C)cc1

Procedure:
Prepared analogously to Example 4 from 7-bromo-6-hydroxy-4,4-dimethyl-4H-3,1-benzoxazin-2-one and 4-(4-methyl-phenylmercapto)-butylchloride.
Reaction SMILES: [C:1]([NH:3][C:4](=[N:7][CH2:8][CH2:9][S:10][CH2:11][C:12]1[C:17]([Cl:18])=[CH:16][CH:15]=[CH:14][N:13]=1)SC)#[N:2].[CH2:19]([NH2:22])[C:20]#[CH:21]>CO>[C:1]([NH:3][C:4]([NH:22][CH2:19][C:20]#[CH:21])=[N:7][CH2:8][CH2:9][S:10][CH2:11][C:12]1[C:17]([Cl:18])=[CH:16][CH:15]=[CH:14][N:13]=1)#[N:2]
Reactant: CSC(=NCCSCc1ncccc1Cl)NC#N
Reactant: C#CCN
Solvent: CO
Product: C#CCNC(=NCCSCc1ncccc1Cl)NC#N
Yield: 67.3 %

Procedure:
A mixture of the product of Step A (3.0 g; 10.0 mmoles) and propargylamine (5.16 g; 93.7 mmoles) in methanol (20 ml) was stirred and heated to reflux temperature under a positive pressure of nitrogen for 16 hours. The reaction mixture was evaporated under reduced pressure and the crude product was recrystallized from isopropyl alcohol with activated carbon treatment to give 2.07 g of the title compound; mp 115°-116°.
Reaction SMILES: [C:1](OC(=O)C)(=[O:3])[CH3:2].C(N(CC)CC)C.[CH3:15][C:16]1[O:20][N:19]=[C:18]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=2)[C:17]=1[C:28]1[CH:33]=[CH:32][C:31]([S:34]([NH2:37])(=[O:36])=[O:35])=[CH:30][CH:29]=1>O1CCCC1>[F:27][C:23]1[CH:22]=[C:21]([C:18]2[C:17]([C:28]3[CH:29]=[CH:30][C:31]([S:34]([NH:37][C:1](=[O:3])[CH3:2])(=[O:36])=[O:35])=[CH:32][CH:33]=3)=[C:16]([CH3:15])[O:20][N:19]=2)[CH:26]=[CH:25][CH:24]=1
Reactant: Cc1onc(-c2cccc(F)c2)c1-c1ccc(S(N)(=O)=O)cc1
Reactant: CC(=O)OC(C)=O
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CC(=O)NS(=O)(=O)c1ccc(-c2c(-c3cccc(F)c3)noc2C)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 80.7 %

Procedure:
Acetic anhydride (1.01 g, 9.39 mmol) and triethylamine (0.401 g, 3.97 mmol) were added to a solution of 4-[5-methyl-3-(3-fluorophenyl)isoxazol-4-yl]benzenesulfonamide (1.10 g, 3.31 mmol) and N,N-dimethylpyridine (0.202 g) in dry tetrahydrofuran. After stirring for 18 hours at room temperature, the reaction mixture was concentrated. The residue was dissolved in ethyl acetate, washed successively with 1N hydrochloric acid and brine, dried over anhydrous MgSO4 and concentrated to afford 1.0 g (81%) of the desired product as a crystalline product: mp 144-145° C. 1H NMR (CDCl3) 8.00 (d, 2H, J=7.3 Hz), 7.30-7.27 (m, 4H), 7.10-7.06 (m, 3H), 2.46 (s, 3H), 1.99 (s, 3H). Anal. Calc'd for C18H15FN2O4S: C, 57.75; H, 4.04; N, 7.48. Found: C, 57.84; H, 4.06; N, 7.49.
Reaction SMILES: [NH:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[C:3](/[CH:10]=[C:11]2\[O:12][C:13]3[C:20]([CH2:21][N:22]4[CH2:27][CH2:26][N:25](C(OC(C)(C)C)=O)[CH2:24][CH2:23]4)=[CH:19][CH:18]=[CH:17][C:14]=3[C:15]\2=[O:16])=[CH:2]1.Cl>C(Cl)Cl.O1CCOCC1>[NH:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[C:3](/[CH:10]=[C:11]2\[O:12][C:13]3[C:20]([CH2:21][N:22]4[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]4)=[CH:19][CH:18]=[CH:17][C:14]=3[C:15]\2=[O:16])=[CH:2]1
Reactant: CC(C)(C)OC(=O)N1CCN(Cc2cccc3c2O/C(=C\c2c[nH]c4ncccc24)C3=O)CC1
Agent: Cl
Solvent: C1COCCO1
Solvent: ClCCl
Product: O=C1/C(=C/c2c[nH]c3ncccc23)Oc2c(CN3CCNCC3)cccc21
Temperature: 25 °C
Reaction time: 2 h
Yield: 96 %

Procedure:
A solution of tert-butyl (Z)-4-({2-[(1H-pyrrolo[2,3-b]pyridin-3-yl)methylene]-3-oxo-2,3-dihydrobenzofuran-7-yl}methyl)piperazine-1-carboxylate (0.0269 g, 0.0584 mmol) in methylene chloride (2 mL) was added with a 4 M solution of hydrogen chloride in 1,4-dioxane (2 mL), and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated, the resulting residue was added with saturated aqueous sodium hydrogencarbonate, and the mixture was extracted three times with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate, and then the solvent was evaporated to obtain (Z)-2-[(1H-pyrrolo[2,3-b]pyridin-3-yl)methylene]-7-(piperazin-1-ylmethyl)benzofuran-3(2H)-one (0.0202 g, 96%).
Reaction SMILES: [CH3:1][C:2]1[S:3][C:4]2[C:13]3[N:12]=[C:11]([NH2:14])[N:10]=[CH:9][C:8]=3[CH2:7][CH2:6][C:5]=2[N:15]=1.[C:16](Cl)(=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.O>N1C=CC=CC=1>[CH3:1][C:2]1[S:3][C:4]2[C:13]3[N:12]=[C:11]([NH:14][C:16](=[O:23])[C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)[N:10]=[CH:9][C:8]=3[CH2:7][CH2:6][C:5]=2[N:15]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: Cc1nc2c(s1)-c1nc(N)ncc1CC2
Solvent: O
Solvent: c1ccncc1
Product: Cc1nc2c(s1)-c1nc(NC(=O)c3ccccc3)ncc1CC2
Temperature: 25 °C
Reaction time: 2 h
Yield: 58.3 %

Procedure:
To 2-methyl-4,5-dihydro-thiazolo[4,5-h]quinazolin-8-ylamine (0.2 g, 0.92 mmol) in pyridine (7 mL) was added benzoyl chloride (117 μL, 142 mg, 1 mmol). The mixture was stirred at room temperature for 2 h. Water (100 mL) was added and the product was extracted into EtOAc (3×50 mL). The organic extracts were combined, dried, filtered, and concentrated under vacuum. Flash column chromatography (50% EtOAc:hexane) followed by crystallisation from EtOH afforded the title product as yellow crystals (173 mg, 59%): mp 229-231° C. Anal. RP-HPLC: tR 13.5 min (0-60% MeCN, purity 100%). 1H-NMR (CDCl3): δ 8.59 (s, 1H, NH), 8.44 (s, 1H, Py-H), 7.95 (m, 2H, Ph-H), 7.54 (m, 3H, Ph-H), 3.09 (m, 4H, CH2—CH2), 2.77 (s, 3H, CH3). 13C-NMR (CDCl3): δ 170.70, 165.50, 160.05, 158.04, 157.02, 155.77, 134.89, 132.66, 129.15, 128.92, 127.89, 121.44, 25.39, 24.50, 20.31. MS (ESI+): m/z 323.05 (M+H)+. Anal. (C17H14N4OS)C, H, N.