Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:4]=1[CH2:5][N:6]1[C:10](=[O:11])[CH2:9][NH:8][S:7]1(=[O:13])=[O:12].[CH3:20][O:21][C:22]([C:24]1[CH:25]=[C:26](B(O)O)[CH:27]=[CH:28][CH:29]=1)=[O:23]>O1CCOCC1.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH3:20][O:21][C:22](=[O:23])[C:24]1[CH:25]=[CH:26][CH:27]=[C:28]([N:8]2[CH2:9][C:10](=[O:11])[N:6]([CH2:5][C:4]3[CH:14]=[CH:15][C:16]([O:18][CH3:19])=[CH:17][C:3]=3[O:2][CH3:1])[S:7]2(=[O:13])=[O:12])[CH:29]=1
Reactant: COC(=O)c1cccc(B(O)O)c1
Reactant: COc1ccc(CN2C(=O)CNS2(=O)=O)c(OC)c1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: C1COCCO1
Product: COC(=O)c1cccc(N2CC(=O)N(Cc3ccc(OC)cc3OC)S2(=O)=O)c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A solution of the title B compound in Example 36, 2-(2,4-dimethoxybenzyl)-1,1-dioxo-1,2,5-thiadiazolidin-3-one (115 mg, 4.02 mmol) and 3-methoxycarbonyl phenylboronic acid (145 mg, 8.04 mmol) in 1,4-dioxane (5 mL) is treated with copper(II) acetate (110 mg, 6.03 mmol) and CS2CO3 (262 mg, 8.04 mmol). The mixture is stirred at RT for 16 h and the solvent is evaporated. The residue is partitioned between EtOAc and 1N aqueous HCl. The organic layer is dried over anhydrous Na2SO4 and concentrated. The residue is flash chromatographed on silica gel using 30% EtOAc in hexanes as the eluent to give 3-[5-(2,4-dimethoxybenzyl)-1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl]benzoic acid methyl ester as a clear oil: [M+NH4]+=438.
Reaction SMILES: [O:1]=[C:2]1[NH:10][C:9]2[C:4](=[N:5][C:6]([C:11]3[CH:12]=[N:13][N:14]4[CH:19]=[CH:18][C:17]([C:20]#[N:21])=[CH:16][C:15]=34)=[N:7][CH:8]=2)[N:3]1[CH:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1.Br[CH2:29][CH2:30][O:31][Si:32]([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33]>CN(C=O)C.[H-].[Na+]>[Si:32]([O:31][CH2:30][CH2:29][N:10]1[C:9]2[C:4](=[N:5][C:6]([C:11]3[CH:12]=[N:13][N:14]4[CH:19]=[CH:18][C:17]([C:20]#[N:21])=[CH:16][C:15]=34)=[N:7][CH:8]=2)[N:3]([CH:22]2[CH2:23][CH2:24][O:25][CH2:26][CH2:27]2)[C:2]1=[O:1])([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33]
Reactant: N#Cc1ccn2ncc(-c3ncc4[nH]c(=O)n(C5CCOCC5)c4n3)c2c1
Reactant: CC(C)(C)[Si](C)(C)OCCBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)OCCn1c(=O)n(C2CCOCC2)c2nc(-c3cnn4ccc(C#N)cc34)ncc21
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 75.6 %

Procedure:
To a solution of example 1 (50 mg, 0.14 mmol) in DMF (8 mL), 55-65% NaH dispersion in mineral oil (6 mg, 0.15 mmol) was added. The resulting solution was stirred at room temperature for 10 min. Then (2-bromoethoxy)-tert-butyldimethylsilane (0.074 mL, 0.34 mmol) was added and the reaction was stirred at 50° C. for 14.5 h. The reaction mixture was quenched with H2O (10 mL) and extracted with EtOAc (3×10 mL). The combined organic phases were dried over anhydrous Na2SO4, filtered and concentrated. The crude product thus obtained was chromatographed over silica gel using hexanes/EtOAc mixtures of increasing polarity as eluent, to afford 55 mg of the desired compound (76% yield).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([S:9](Cl)(=[O:11])=[O:10])[CH:6]=[CH:7][CH:8]=1.[NH2:13][C:14]1[CH:26]=[CH:25][C:24]2[C:23]3[C:18](=[CH:19][C:20]([NH2:27])=[CH:21][CH:22]=3)[C:17](=[O:28])[C:16]=2[CH:15]=1>C1COCC1.N1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([S:9]([NH:13][C:14]2[CH:26]=[CH:25][C:24]3[C:23]4[C:18](=[CH:19][C:20]([NH:27][S:9]([C:5]5[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=5)(=[O:11])=[O:10])=[CH:21][CH:22]=4)[C:17](=[O:28])[C:16]=3[CH:15]=2)(=[O:11])=[O:10])[CH:6]=[CH:7][CH:8]=1
Reactant: Nc1ccc2c(c1)C(=O)c1cc(N)ccc1-2
Reactant: COc1cccc(S(=O)(=O)Cl)c1
Solvent: C1CCOC1
Solvent: c1ccncc1
Product: COc1cccc(S(=O)(=O)Nc2ccc3c(c2)C(=O)c2cc(NS(=O)(=O)c4cccc(OC)c4)ccc2-3)c1
Reaction time: 0.5 h
Yield: 55.4 %

Procedure:
3-Methoxybenzenesulfonyl chloride (4.75 g, 23.0 mmol) in THF (40 mL) was treated with the product from Example 16A (5.05 g, 24 mmol) in THF (60 mL) and pyridine (60 mL) over 10 minutes. After an additional 30 minutes, the mixture was quenched with a mixture of 1.0M (pH 6) aqueous potassium phosphate buffer (30 mL) and brine (20 mL). The aqueous phase was separated and extracted with diethyl ether. The organic phases were combined, washed 1.0M (pH 6) aqueous potassium phosphate buffer (10 mL) and brine (10 mL), and the aqueous phase was extracted with diethyl ether. All the organic phases were combined, dried (Na2SO4), concentrated, and the filtrate concentrated under reduced pressure. The residue was purified by flash chromatography (ethyl acetate/CH2Cl2). The appropriate fractions were concentrated, dissolved in a small quantity of hot methanol and triturated with diethyl ether. The resulting precipitate was collected by filtration and washed with (10% methanol/diethyl ether) to provide the title compound as an orange powder (3.51 g). 1H HNMR (DMSO-d6) δ 10.55 (bs, 2H), 7.53 (d, J=8.5 Hz, 2H), 7.47 (t, J=8.0 Hz, 2H), 7.33 (d, J=7.6 Hz, 2H), 7.28-7.24 (m, 6H), 7.18 (dd, J=8.5, 2.1, 2H), 3.77 (s, 6H); MS calculated for (M+H): 550.0868; observed: 550.0848; IR 3232, 2971, 1719, 1599, 1466, 1256, 1155.
Reaction SMILES: [Br:1][C:2]1[C:3](=[O:9])[NH:4][C:5]([Cl:8])=[N:6][CH:7]=1.[CH3:10]N(C=O)C.[H-].[Li+].IC>COCCOC>[Br:1][C:2]1[C:3](=[O:9])[N:4]([CH3:10])[C:5]([Cl:8])=[N:6][CH:7]=1
Reactant: CN(C)C=O
Reactant: O=c1[nH]c(Cl)ncc1Br
Agent: [H-]
Agent: [Li+]
Solvent: COCCOC
Solvent: CI
Product: Cn1c(Cl)ncc(Br)c1=O
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 72 %

Procedure:
To a solution of 5-bromo-2-chloropyrimidin-4(3H)-one (1.00 g, 4.78 mmol) in DME (12 mL)/DMF (3 mL) under nitrogen at 0° C., LiH (0.044 g, 5.25 mmol) was added, and the reaction mixture was stirred for 15 minutes at room temperature. Iodomethane (0.589 mL, 9.45 mmol) was then added and the reaction mixture was stirred at room temperature for 30 minutes and then at 60° C. for 1.5 hours. The reaction mixture was quenched with H2O and then partitioned between EtOAc and saturated aqueous NaCl. The phases were separated, and the aqueous phase was re-extracted with EtOAc (1×). The combined organic layers were dried (Na2SO4), filtered and concentrated to yield a crude yellow oil. The crude product was purified by flash column chromatography, eluting with 25:1 dichloromethane/EtOAc. The desired product (0.764 g, 72%) was obtained as a yellow crystalline solid. 1H NMR (400 MHz, DMSO-d6) δ 8.26 (s, 1H), 3.59 (s, 3H). LRMS (ESI pos) m/e 223, 225 (M+, Br pattern).
Reaction SMILES: [OH:1][C:2]1[C:3]([O:14][CH3:15])=[CH:4][C:5]([N+:11]([O-])=O)=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8]>CO.O=[Pt]=O>[NH2:11][C:5]1[CH:4]=[C:3]([O:14][CH3:15])[C:2]([OH:1])=[CH:10][C:6]=1[C:7]([OH:9])=[O:8]
Reactant: COc1cc([N+](=O)[O-])c(C(=O)O)cc1O
Agent: O=[Pt]=O
Solvent: CO
Product: COc1cc(N)c(C(=O)O)cc1O
Reaction time: 4 h
Yield: 97.4 %

Procedure:
5-Hydroxy-4-methoxy-2-nitro-benzoic acid (18 g, 84.51 mmol, J Indian Chem. Soc. 1970, 70, 925) is suspended in MeOH (1 L) and treated PtO2 (100 mg). The flask is flushed with hydrogen gas and the reaction mixture is stirred under hydrogen atmosphere (45 psi) for 4 hours. The reaction mixture is filtered through a celite plug and the solvent is removed under reduced pressure. The crude product is redissolved in DCM, dried (MgSO4) and concentrated to yield 15.06 g (82.3 mmol, 97%) of the desired product.
Reaction SMILES: Cl.[F:2][C:3]1[CH:4]=[C:5]([C:9]2[N:14]=[CH:13][C:12]([C:15]3[CH:16]=[N:17][CH:18]=[C:19]([CH3:21])[CH:20]=3)=[CH:11][C:10]=2[C:22](O)=[O:23])[CH:6]=[CH:7][CH:8]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[CH3:39][O:40][C:41]1[CH:42]=[CH:43][C:44]([CH2:49][NH2:50])=[N:45][C:46]=1[O:47][CH3:48].CN1CCOCC1>CN(C)C=O>[CH3:39][O:40][C:41]1[CH:42]=[CH:43][C:44]([CH2:49][NH:50][C:22]([C:10]2[CH:11]=[C:12]([C:15]3[CH:16]=[N:17][CH:18]=[C:19]([CH3:21])[CH:20]=3)[CH:13]=[N:14][C:9]=2[C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([F:2])[CH:4]=2)=[O:23])=[N:45][C:46]=1[O:47][CH3:48]
Reactant: Cc1cncc(-c2cnc(-c3cccc(F)c3)c(C(=O)O)c2)c1
Reactant: COc1ccc(CN)nc1OC
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: ClCCCl
Solvent: CN1CCOCC1
Product: COc1ccc(CNC(=O)c2cc(-c3cncc(C)c3)cnc2-c2cccc(F)c2)nc1OC
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
To a solution of 6-(3-fluorophenyl)-5′-methyl-3,3′-bipyridine-5-carboxylic acid hydrochloride (3-6, prepared by the method described above for the preparation of 3-4, 2.5 g, 7.25 mmol) in dimethylformamide (36 mL) cooled to 0° C., was added EDC (1.95 g, 10.2 mmol) and HOBt (1.67 g, 10.9 mmol) followed by 1-(5,6-dimethoxypyridin-2-yl)methanamine (11-6, 1.46 g, 8.7 mmol) and N-methylmorpholine (4.78 mL, 43.5 mmol). The reaction stirred for 15 minutes and then was allowed to warm to room temperature. After 3.5 hours the reaction mixture was partitioned between ethyl acetate and saturated sodium bicarbonate. The organics were washed with water and brine, dried over Na2SO4/MgSO4, filtered and stripped to dryness. The crude product was recrystallized from chloroform/ethyl ether to afford the title compound (3-7) as a white solid. 1H NMR (500 MHz, CDCl3) δ 8.96 (d, J=2.2 Hz, 1H), 8.72 (d, J=1.7 Hz, 1H), 8.56 (s, 1H), 8.23 (d, J=2.2 Hz, 1H), 7.76 (s, 1H), 7.44 (d, J=7.8 Hz, 1H), 7.40 (d, J=9.5 Hz, 1H), 7.24 (m, 1H), 6.99 (m, 2H), 6.74 (d, J=7.8 Hz, 1H), 6.33 (m, 1H), 4.44 (d, J=5.4 Hz, 2H), 3.88 (s, 3H), 3.76(s, 3H), 2.45 (s, 3H). HRMS [M+H] C26H23FN4O3 calc'd 459.1827, found 459.1832.
Reaction SMILES: [NH2:1][C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[CH:10][CH:9]=2)[N:5]=[C:4]([CH3:21])[C:3]=1[C:22](O)([CH2:28][C:29]([O:31]CC)=O)[C:23]([O:25][CH2:26][CH3:27])=[O:24]>CC(O)=O>[OH:31][C:29]1[CH:28]=[C:22]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:3]2[C:4]([CH3:21])=[N:5][N:6]([CH2:7][C:8]3[CH:9]=[CH:10][C:11]([O:14][C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=4)=[CH:12][CH:13]=3)[C:2]=2[N:1]=1
Reactant: CCOC(=O)CC(O)(C(=O)OCC)c1c(C)nn(Cc2ccc(Oc3ccccc3)cc2)c1N
Solvent: CC(=O)O
Product: CCOC(=O)c1cc(O)nc2c1c(C)nn2Cc1ccc(Oc2ccccc2)cc1
Yield: 67.4 %

Procedure:
A suspension of diethyl 2-(5-amino-3-methyl-1-(4-phenoxybenzyl)-1H-pyrazol-4-yl)-2-hydroxysuccinate (crude from above) (2.31 mmol) from x in glacial AcOH (14 mL) was refluxed for 2 h. The mixture was concentrated under reduced pressure as much as possible. Then MeOH was added and the product crystallized as a white solid which was filtered, washed with cold MeOH and dried in a vacuum oven to provide the title compound (628 mg, 67% over two steps) as a tan solid. 1H NMR (500 MHz, CDCl3) δ 7.40 (d, J=8.3 Hz, 2H), 7.31 (t, J=7.3 Hz, 2H), 7.09 (t, J=7.4 Hz, 1H), 6.97 (d, J=8.0 Hz, 2H), 6.92 (d, J=8.4 Hz, 2H), 6.78 (s, 1H), 5.50 (s, 2H), 4.44 (q, J=7.1 Hz, 2H), 2.53 (s, 3H), 1.43 (t, J=7.1 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 164.83, 164.75, 157.17, 156.81, 143.45, 143.12, 139.06, 130.59, 129.72, 129.51, 123.43, 119.11, 118.70, 113.27, 103.16, 62.13, 50.60, 15.44, 14.16. ESI MS: m/z 404.1 (M+H)+.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]2[CH:15]=[C:16]3[C:21](=[CH:22][CH:23]=2)[NH:20][C:19](=[O:24])[CH2:18][CH2:17]3)=[CH:4][CH:3]=1.[OH:25]O>>[OH:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]2[CH:15]=[C:16]3[C:21](=[CH:22][CH:23]=2)[NH:20][C:19](=[O:24])[CH2:18][CH2:17]3)=[O:25])=[CH:4][CH:3]=1
Reactant: OO
Reactant: O=C1CCc2cc(OCCCCSc3ccc(O)cc3)ccc2N1
Product: O=C1CCc2cc(OCCCCS(=O)c3ccc(O)cc3)ccc2N1

Procedure:
Prepared analogous to Example 2 from 6-[4-(4-hydroxy-phenyl-mercapto)-butoxy]-3,4-dihydro-carbostyril and hydrogen peroxide.
Reaction SMILES: Cl.[O:2]=[C:3]1[N:7]([C:8]2[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][CH:9]=2)[CH2:6][C:5]2([CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)[O:4]1.[Br:23][C:24]1[CH:29]=[C:28]([CH2:30]Br)[CH:27]=[CH:26][C:25]=1[C:32]([F:35])([F:34])[F:33]>>[Br:23][C:24]1[CH:29]=[C:28]([CH:27]=[CH:26][C:25]=1[C:32]([F:33])([F:34])[F:35])[CH2:30][N:20]1[CH2:21][CH2:22][C:5]2([O:4][C:3](=[O:2])[N:7]([C:8]3[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][CH:9]=3)[CH2:6]2)[CH2:18][CH2:19]1
Reactant: COC(=O)c1ccc(N2CC3(CCNCC3)OC2=O)cc1
Reactant: FC(F)(F)c1ccc(CBr)cc1Br
Agent: Cl
Product: COC(=O)c1ccc(N2CC3(CCN(Cc4ccc(C(F)(F)F)c(Br)c4)CC3)OC2=O)cc1

Procedure:
The title compound was prepared from methyl 4-(2-oxo-1-oxa-3,8-diazaspiro[4.5]dec-3-yl)benzoate hydrochloride salt (50 mg, 0.153 mmol; Example 1, Step 2) and 2-bromo-4-(bromomethyl)-1-(trifluoromethyl)benzene (53.5 mg, 0.168 mmol) following essentially the same procedure described in Step 1 of Example 7-9. The title compound was obtained as a yellow oil (91 mg) that was used without any further purification.
Reaction SMILES: [C:1]1([CH2:7][C:8]#[N:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:10]([Mg]Br)[CH3:11].B(F)(F)F.[OH-].[Na+]>C(OCC)C.C(OCC)(=O)C>[CH2:7]([C:8]1([NH2:9])[CH2:11][CH2:10]1)[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC[Mg]Br
Reactant: N#CCc1ccccc1
Agent: FB(F)F
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: CCOCC
Product: NC1(Cc2ccccc2)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 95.5 %

Procedure:
To a solution of phenylacetonitrile (3 g, 25.61 mmol) and tetraisopropylorthotitanate (8 ml, 27.15 mmol) in diethyl ether (Et2O)/tetrahydrofuran (THF) (1/1, 100 ml) ethyl-magnesiumbromide (49.33 mmol) was added at room temperature. The exothermic mixture was stirred for 1 h at room temperature. Then BF3×Et2O (49.34 mmol) was added and the mixture was stirred for 1 h. The mixture was poured into a cold aqueous solution of NaOH (10%) and diluted with ethyl acetate. The mixture was filtered, and the organic layer was washed with water and brine, dried over MgSO4, filtered, and the solvent evaporated under reduced pressure to give the product as a yellow oil (3.6 g, 96%).
Reaction SMILES: [Cl:1][C:2]1[CH:34]=[CH:33][C:5]([CH2:6][O:7][C:8]2[CH:9]=[CH:10][C:11]([C:14]([F:32])([F:31])[C:15]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=3[F:30])([OH:22])[CH2:16][N:17]3[CH:21]=[N:20][N:19]=[N:18]3)=[N:12][CH:13]=2)=[C:4](F)[CH:3]=1.BrCC1C=CC(Cl)=CC=1>>[Cl:1][C:2]1[CH:34]=[CH:33][C:5]([CH2:6][O:7][C:8]2[CH:9]=[CH:10][C:11]([C:14]([F:32])([F:31])[C:15]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=3[F:30])([OH:22])[CH2:16][N:17]3[CH:21]=[N:20][N:19]=[N:18]3)=[N:12][CH:13]=2)=[CH:4][CH:3]=1
Reactant: OC(Cn1cnnn1)(c1ccc(F)cc1F)C(F)(F)c1ccc(OCc2ccc(Cl)cc2F)cn1
Agent: Clc1ccc(CBr)cc1
Product: OC(Cn1cnnn1)(c1ccc(F)cc1F)C(F)(F)c1ccc(OCc2ccc(Cl)cc2)cn1

Procedure:
Compound 4 was prepared in a similar manner to compound 1 from 1-(bromomethyl)-4-chlorobenzene to afford a syrup (0.04 g, 0.08 mmol, 28.7%). 1H NMR (500 MHz, CDCl3): δ 8.73 (s, 1H), 8.23 (d, J=2.0 Hz, 1H), 7.51 (d, J=8.5 Hz, 2H), 7.40 (d, J=8.5 Hz, 2H), 7.34-7.29 (m, 2H), 7.28 (dd, J=9.0, 3.0 Hz, 1H), 6.77-6.73 (m, 1H), 6.67 (t, J=7.0 Hz, 1H), 5.55 (d, J=14 Hz, 1H), 5.09 (s, 2H), 5.08 (d, J=14.5 Hz, 2H). MS (ESI): m/z 494.1 [M++1].
Reaction SMILES: C([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C@@H:15]2[CH2:19][CH2:18][CH2:17][N:16]2[CH3:20])[CH2:10][CH2:9]1)C1C=CC=CC=1.[H][H]>C1COCC1.[Pd]>[CH3:20][N:16]1[CH2:17][CH2:18][CH2:19][C@H:15]1[CH2:14][N:11]1[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]1
Reactant: [H][H]
Reactant: CN1CCC[C@H]1CN1CCN(Cc2ccccc2)CC1
Agent: [Pd]
Solvent: C1CCOC1
Product: CN1CCC[C@H]1CN1CCNCC1
Yield: 94.1 %

Procedure:
To a solution of (S)-1-benzyl-4-[(1-methylpyrrolidin-2-yl)methyl]piperazine 0.71 g (2.61 mmol) in 40 ml THF was added 10% Pd/C 0.4 g and exposed to 1 atm hydrogen overnight. The reaction mixture was filtered. The filtrate was concentrated to give 0.450 g of desired product in 94% yield.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:16]3[C:12]([S:13][C:14]4[CH:20]=[CH:19][CH:18]=[CH:17][C:15]=43)=[C:11]([C:21]([O-])=[O:22])[C:10]=2[C:24]([O-])=[O:25])=[CH:5][CH:4]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[H-].[NH4+].[OH-]>ClCCl.CCOCC.O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[N:16]3[C:12]([S:13][C:14]4[CH:20]=[CH:19][CH:18]=[CH:17][C:15]=43)=[C:11]([CH2:21][OH:22])[C:10]=2[CH2:24][OH:25])=[CH:7][CH:8]=1
Reactant: COc1ccc(-c2c(C(=O)[O-])c(C(=O)[O-])c3sc4ccccc4n23)cc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: ClCCl
Solvent: CCOCC
Solvent: O
Product: COc1ccc(-c2c(CO)c(CO)c3sc4ccccc4n23)cc1
Reaction time: 0.33 h

Procedure:
A solution of 1-(4-methoxyphenyl)benzo[d]pyrrolo[2,1-b]thiazole-2,3-dicarboxylate (1.7 g, 4.3 mmol) in anhydrous dichloromethane (30 mL) was added dropwise to a stirred mixture of lithium aluminum hydride (0.4 g, 10.0 mmol) in anhydrous ether (20 mL) at −5° C. to 0° C. The reaction mixture was allowed to stir at this temperature for 20 min. The excess hydride was decomposed by adding water (1 mL) followed by NH4OH (1 mL) and water (1 mL) at −5° C. to 0° C. The mixture was filtered through a pad of Celite, washed with several times with dichloromethane. The combined filtrate and washings were washed successively with water and brine solution. The organic layer was dried (Na2SO4) and concentrated to dryness in vacuo. The residue was crystallized from ethanol to give (1-(4-methoxyphenyl)benzo[d]pyrrolo[2,1-b]thiazole-2,3-diyl)-dimethanol (BO-1646), 1.3 g (91%); mp 156-157° C. 1H NMR (DMSO-d6) δ 3.85 (3H, s, MeO), 4.22 (2H, d, J=4.8 Hz, CH2), 4.66 (3H, m, CH2 and exchangeable OH), 5.09 (1H, t, J=4.8 Hz, exchangeable, OH), 6.85-6.87 (1H, m, ArH), 7.08-7.19 (4H, m, 4×ArH), 7.39-7.42 (2H, m, 2×ArH), 7.76-7.79 (1H, m, ArH). Anal. Calcd. for (C19H17NO3S): C, 67.24; H, 5.05; N, 4.13; S, 9.45. Found: C, 67.54; H, 5.00; N, 4.00; S, 9.30.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]#[N:9])[CH:3]=1.[CH3:10][S-:11].[Na+].C(OCC)(=O)C.O>C1COCC1>[C:8]([C:4]1[CH:3]=[C:2]([S:11][CH3:10])[CH:7]=[CH:6][N:5]=1)#[N:9]
Reactant: C[S-]
Reactant: N#Cc1cc(Cl)ccn1
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Solvent: CCOC(C)=O
Product: CSc1ccnc(C#N)c1
Yield: 100.1 %

Procedure:
4-Chloro-2-cyanopyridine (2.18 g, 15.7 mmol) and sodium thiomethoxide (2.20 g, 31.4 mmol) were dissolved in THF (100 ml), and the mixture was refluxed for 2 hrs. The reaction mixture was combined with ethyl acetate and water. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated to give the titled compound (2.36 g, 99%) as pale yellow crystals.
Reaction SMILES: [CH2:1]([O:3][C:4]1[N:9]=[C:8]([F:10])[CH:7]=[C:6]([NH:11][NH2:12])[N:5]=1)[CH3:2].[C:13](=S)=[S:14].OO.C(N(CC)CC)C.Cl>O.C(#N)C>[CH2:1]([O:3][C:4]1[N:5]2[C:13](=[S:14])[NH:12][N:11]=[C:6]2[CH:7]=[C:8]([F:10])[N:9]=1)[CH3:2]
Reactant: S=C=S
Reactant: CCOc1nc(F)cc(NN)n1
Agent: Cl
Agent: OO
Solvent: CCN(CC)CC
Solvent: CC#N
Solvent: O
Product: CCOc1nc(F)cc2n[nH]c(=S)n12

Procedure:
A mixture containing approximately 5.2 g (30 mmol) of 2-ethoxy-4-fluoro-6-hydrazinopyrimidine in a solvent composed of 50 mL of acetonitrile and 15 mL of water was prepared and to this was added 6.4 mL (107 mmol) of carbon disulfide at ambient temperature with stirring. The heterogeneous white mixture became a pale yellow solution after about 10 min and then 3.8 mL of 30 percent aqueous hydrogen peroxide (37 mmol) and 3.2 mL of water were added over a 30-min period with stirring and cooling to hold the temperature at about 25° C. The mixture was allowed to react another 10 min and then 3.22 g (32 mmol) of triethylamine was added and the resulting mixture filtered to remove sulfur. The filtrate was acidified with 10 mL of 3.75N hydrochloric acid (38 mmol). The resulting mixture was filtered to recover the precipitate that formed. This was washed with water and dried to obtain 4.4 g (66 percent of theory) of the title compound of 97 percent purity as a light beige solid melting at 170° C. Considerable product remained in the filtrate.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([C:15]2[S:16][C:17]([C:21](O)=[O:22])=[C:18]([CH3:20])[N:19]=2)[C:11](=[O:24])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[S:55]1[C:59]([CH2:60][NH2:61])=[CH:58][C:57]2[CH:62]=[CH:63][CH:64]=[CH:65][C:56]1=2>CN(C)C=O>[S:55]1[C:59]([CH2:60][NH:61][C:21]([C:17]2[S:16][C:15]([N:12]3[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)=[CH:10][C:11]3=[O:24])=[N:19][C:18]=2[CH3:20])=[O:22])=[CH:58][C:57]2[CH:62]=[CH:63][CH:64]=[CH:65][C:56]1=2
Reactant: NCc1cc2ccccc2s1
Reactant: Cc1nc(-n2ccc(OCc3ccccc3)cc2=O)sc1C(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: Cc1nc(-n2ccc(OCc3ccccc3)cc2=O)sc1C(=O)NCc1cc2ccccc2s1
Reaction time: 0.5 h
Yield: 78 %

Procedure:
To a solution of 2-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-4-methylthiazole-5-carboxylic acid (0.20 g, 0.58 mmol) in anhydrous N,N-dimethylformamide (10 mL) was added N,N-diisopropylethylamine (0.27 g, 2.10 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (0.18 g, 0.93 mmol). The mixture was stirred for 30 minutes, followed by the addition of 1-hydroxybenzotriazole (0.11 g, 0.81 mmol) and benzo[b]thiophen-2-ylmethanamine (0.14 mL, 0.87 mmol). The reaction mixture was stirred at ambient temperature for 24 hours. The solvent was removed in vacuo and the residue was dissolved in dichloromethane (50 mL), washed with saturated aqueous sodium bicarbonate (2×5 mL) and brine (10 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was recrystallized from ethyl acetate and hexane. The solid was collected by filtration and washed with methanol and hexane. The title compound was obtained as a colorless solid in 78% yield (0.22 g): 1H NMR (300 MHz, DMSO-d6) δ 8.98 (t, J=5.8 Hz, 1H), 8.61 (d, J=8.1 Hz, 1H), 7.82-7.85 (m, 1H), 7.76-7.73 (m, 1H), 7.51-7.23 (m, 8H), 6.34 (dd, J=8.1, 2.7 Hz, 1H), 6.23 (d, J=2.7 Hz, 1H), 5.16 (s, 2H), 4.65-4.63 (m, 2H), 2.56 (s, 3H); MS (ES+) m/z 488.1 (M+1).
Reaction SMILES: [N:1]([CH:4]([C:6]1[N:7]=[C:8]2[S:22][CH:21]=[C:20]([CH3:23])[N:9]2[C:10](=[O:19])[C:11]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[F:18])[CH3:5])=[N+]=[N-].CP(C)C>O1CCCC1>[NH2:1][CH:4]([C:6]1[N:7]=[C:8]2[S:22][CH:21]=[C:20]([CH3:23])[N:9]2[C:10](=[O:19])[C:11]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[F:18])[CH3:5]
Reactant: Cc1csc2nc(C(C)N=[N+]=[N-])c(-c3ccccc3F)c(=O)n12
Agent: CP(C)C
Solvent: C1CCOC1
Product: Cc1csc2nc(C(C)N)c(-c3ccccc3F)c(=O)n12
Temperature: 25 °C
Reaction time: 1 h
Yield: 101.4 %

Procedure:
To a stirred solution of 7-(1-azidoethyl)-6-(2-fluorophenyl)-3-methyl-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one (0.087 g, 0.26 mmol) in tetrahydrofuran (3 mL) was added 1.00 M of trimethylphosphine in tetrahydrofuran (0.32 mL, 0.32 mmol), and the mixture was stirred at room temperature for 1 hour. The mixture was concentrated to give the crude product (0.080 g), which was used directly in next step. LCMS calculated for C15H15FN3OS (M+H)+: m/z=304.1. Found: 304.0.