Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([C:8]1[C:13]([O:14]COC)=[CH:12][CH:11]=[C:10]([Sn](CCCC)(CCCC)CCCC)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.COC[O:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1I>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.C1(C)C(C)=CC=CC=1>[CH2:1]([C:8]1[C:13]([OH:14])=[CH:12][CH:11]=[C:10]([C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=2[OH:34])[N:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccc(OCOC)c(Cc2ccccc2)n1
Reactant: COCOc1ccccc1I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1C
Product: Oc1ccccc1-c1ccc(O)c(Cc2ccccc2)n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 15.9 %

Procedure:
A mixture of 641 mg of (2-benzyl-3-methoxymethyloxy-6-pyridyl)tributyltin (Production Example 18), 327 mg of 2-methoxymethyloxyiodobenzene (Production Example 20), 71.6 mg of tetrakis(triphenylphosphine)palladium(0) and 7 ml of xylene was heated under refluxed for one hour in nitrogen atmosphere. After cooling as it was, the mixture was filtered through silica gel and the solvent was removed. To the residue was added 2 ml of trifluoroacetic acid, followed by stirring at room temperature overnight. The reaction solution was neutralized by aqueous potassium carbonate. Ethyl acetate was added thereto, and the organic phase was washed with water and brine, dried over anhydrous magnesium sulfate and the solvent was removed. The residue was subjected to silica gel column chromatography using 30% ethyl acetate/hexane, to give 54.5 mg of the target compound.
Reaction SMILES: [Cl:1][C:2]1[CH:19]=[CH:18][C:5]([C@@H:6]([C@@H:11]2[CH2:16][CH2:15][CH2:14][CH2:13][C@H:12]2[OH:17])[CH2:7][N+:8]([O-])=O)=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].O1CCCC1.O>O1CCCC1>[NH2:8][CH2:7][C@H:6]([C@@H:11]1[CH2:16][CH2:15][CH2:14][CH2:13][C@H:12]1[OH:17])[C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:19][CH:18]=1
Reactant: O=[N+]([O-])C[C@@H](c1ccc(Cl)cc1)[C@@H]1CCCC[C@H]1O
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: NC[C@@H](c1ccc(Cl)cc1)[C@@H]1CCCC[C@H]1O
Reaction time: 8 h

Procedure:
A solution of 1.9 g (6.7 mmol) of rac-(1R*)-trans-2-[(R*)-4-chloro-α-(nitromethyl)benzyl]cyclohexanol in 30 ml of dry tetrahydrofuran is added dropwise while stirring to a suspension of 1 g of lithium aluminium hydride in 60 ml of dry tetrahydrofuran under argon, whereupon the mixture is stirred at 50° overnight. After cooling the reaction mixture is treated with tetrahydrofuran/water (1:1), the precipitate is filtered off under suction, the filtrate is evaporated, the residue is treated with water and extracted with ether. The rac-(1R*)-trans-2-[(R*)-α-(aminomethyl)-4-chlorobenzyl]cyclohexanol obtained is a colourless oil and is processed directly.
Reaction SMILES: O(P(O[C:18]1[C@H:19]([CH3:42])[C@H:20]2[C@@H:37]([C@H:38]([OH:40])[CH3:39])[C:36](=[O:41])[N:21]2[C:22]=1[C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][C:30]([N+:33]([O-:35])=[O:34])=[CH:29][CH:28]=1)=[O:24])(OC1C=CC=CC=1)=O)C1C=CC=CC=1.FC(F)(F)S(O)(=O)=O.[SH:51][C@@H:52]1[CH2:56][N:55]([C:57]([O:59][CH2:60][C:61]2[CH:66]=[CH:65][C:64]([N+:67]([O-:69])=[O:68])=[CH:63][CH:62]=2)=[O:58])[C@H:54]([CH:70]2[CH2:74][CH2:73][N:72]([CH3:75])[CH2:71]2)[CH2:53]1>>[OH:40][C@@H:38]([C@H:37]1[C:36](=[O:41])[N:21]2[C:22]([C:23]([O:25][CH2:26][C:27]3[CH:28]=[CH:29][C:30]([N+:33]([O-:35])=[O:34])=[CH:31][CH:32]=3)=[O:24])=[C:18]([S:51][C@@H:52]3[CH2:56][N:55]([C:57]([O:59][CH2:60][C:61]4[CH:62]=[CH:63][C:64]([N+:67]([O-:69])=[O:68])=[CH:65][CH:66]=4)=[O:58])[C@H:54]([CH:70]4[CH2:74][CH2:73][N:72]([CH3:75])[CH2:71]4)[CH2:53]3)[C@H:19]([CH3:42])[C@H:20]12)[CH3:39]
Reactant: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(OP(=O)(Oc3ccccc3)Oc3ccccc3)[C@H](C)[C@@H]12
Reactant: CN1CCC([C@@H]2C[C@H](S)CN2C(=O)OCc2ccc([N+](=O)[O-])cc2)C1
Agent: O=S(=O)(O)C(F)(F)F
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@H]3C[C@@H](C4CCN(C)C4)N(C(=O)OCc4ccc([N+](=O)[O-])cc4)C3)[C@H](C)[C@H]12
Yield: 74.5 %

Procedure:
The same procedure as in Example 1-1 was carried out by using p-nitrobenzyl (1R,5S,6S)-2-diphenoxyphosphoryloxy-6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate (680 mg, 1.14 mmol) and (2S,4S)-4-mercapto-2-(N-methylpyrrolidin-3-yl)-N-(p-nitrobenzyloxycarbonyl)pyrrolidine trifluoromethane sulfonate (650 mg, 1.26 mmol, compound of Reference Examples 6-9) to obtain p-nitrobenzyl (1R,5S,6S)-6-[(R)-1-hydroxyethyl]-1-methyl-2-[(2S,4S)-N-(p-nitrobenzyloxycarbonyl)-2-(N-methylpyrrolidin-3-yl)pyrrolidin-4-ylthio]-1-carbapen-2-em-3-carboxylate (603 mg, yield: 74.3%).
Reaction SMILES: [C:1]1(=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[C:7]([NH:11][S:12]([C:15]1[CH:24]=[C:23]([NH:25][NH2:26])[CH:22]=[CH:21][C:16]=1[C:17]([O:19][CH3:20])=[O:18])(=[O:14])=[O:13])([CH3:10])([CH3:9])[CH3:8]>CO>[C:7]([NH:11][S:12]([C:15]1[CH:24]=[C:23]([NH:25][N:26]=[C:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)[CH:22]=[CH:21][C:16]=1[C:17]([O:19][CH3:20])=[O:18])(=[O:14])=[O:13])([CH3:10])([CH3:8])[CH3:9]
Reactant: COC(=O)c1ccc(NN)cc1S(=O)(=O)NC(C)(C)C
Reactant: O=C1CCCC1
Solvent: CO
Product: COC(=O)c1ccc(NN=C2CCCC2)cc1S(=O)(=O)NC(C)(C)C
Temperature: 65 °C
Reaction time: 3 h
Yield: 50.5 %

Procedure:
2.8 g (0.032 mol) of cyclopentanone are added to 2.0 g (0.007 mol) of methyl 2-(N-tert-butylsulfamoyl)-4-hydrazinobenzoate in 100 ml of methanol and the mixture is subsequently stirred at 65° C. for 3 hours. It is evaporated and the residue is triturated with a little methanol. After filtering off with suction and drying, 1.3 g (51% of theory) of methyl 2-(N-tert-butyl-sulfamoyl)-4-cyclopentylidenehydrazinobenzoate are obtained.
Reaction SMILES: C(OC1C=CC2C(=CC=CC=2)N1C(OCC)=O)C.[C:19]([O:23][C:24]([NH:26][C@H:27]([C:30]([OH:32])=O)[CH2:28][OH:29])=[O:25])([CH3:22])([CH3:21])[CH3:20].Cl.[CH3:34][O:35][C:36](=[O:45])[C@@H:37]([CH2:39][CH2:40][C:41]([O:43][CH3:44])=[O:42])[NH2:38].CN1CCOCC1>CN(C)C=O>[CH3:34][O:35][C:36](=[O:45])[C@@H:37]([CH2:39][CH2:40][C:41]([O:43][CH3:44])=[O:42])[NH:38][C:30](=[O:32])[C@H:27]([CH2:28][OH:29])[NH:26][C:24]([O:23][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:25]
Reactant: CC(C)(C)OC(=O)N[C@@H](CO)C(=O)O
Reactant: COC(=O)CC[C@@H](N)C(=O)OC
Agent: CCOC(=O)N1c2ccccc2C=CC1OCC
Agent: Cl
Solvent: CN(C)C=O
Solvent: CN1CCOCC1
Product: COC(=O)CC[C@@H](NC(=O)[C@H](CO)NC(=O)OC(C)(C)C)C(=O)OC
Temperature: 25 °C
Reaction time: 16 h
Yield: 683 %

Procedure:
5.4 g (2.2 mmol) of 2-ethoxy-N-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ) are added to 4.1 g (2 mmol) of tert-butoxycarbonyl-L-serine, 4.23 g (2 mmol) of D-glutamic acid dimethyl ester hydrochloride and 1.01 g (2 mmol) of N-methylmorpholine in 40 ml of dimethylformamide. After stirring for 16 hours at room temperature, the resulting suspension is filtered and the filtrate is evaporated to dryness. The oily residue is taken up in 150 ml of ethyl acetate and, in the cold, is washed 5 times with 50 ml of 2 N citric acid solution each time, then twice with 50 ml of water each time. The organic phase is dried, concentrated to approximately 40 ml and caused to crystallise by adding, in portions, 150 ml of ether/petroleum ether 2:1. 4.95 g (79%) of tert-butoxycarbonyl-L-seryl-D-glutamic acid dimethyl ester are obtained as colourless needles;
Reaction SMILES: [CH3:1][CH:2]([CH2:4][C@@H:5]1[N:14]2[C:15]([C@@:17]([NH:20][C:21]([C@@H:23]3[CH:38]=[C:37]4[C@@H:26]([CH2:27][C:28]5[C:36]6[C:31](=[CH:32][CH:33]=[CH:34][C:35]=64)[NH:30][CH:29]=5)[N:25]([CH3:39])[CH2:24]3)=[O:22])([CH3:19])[O:18][C@@:13]2([OH:40])[C@H:12]2[N:8]([CH2:9][CH2:10][CH2:11]2)[C:6]1=[O:7])=[O:16])[CH3:3].C[Si](C)(C)[Br:43]>CO>[CH3:3][CH:2]([CH2:4][C@@H:5]1[N:14]2[C:15]([C@@:17]([NH:20][C:21]([C@@H:23]3[CH:38]=[C:37]4[C@@H:26]([CH2:27][C:28]5[C:36]6[C:31](=[CH:32][CH:33]=[CH:34][C:35]=64)[NH:30][C:29]=5[Br:43])[N:25]([CH3:39])[CH2:24]3)=[O:22])([CH3:19])[O:18][C@@:13]2([OH:40])[C@H:12]2[N:8]([CH2:9][CH2:10][CH2:11]2)[C:6]1=[O:7])=[O:16])[CH3:1]
Reactant: CC(C)C[C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C)(NC(=O)[C@@H]3C=C4c5cccc6[nH]cc(c56)C[C@H]4N(C)C3)C(=O)N12
Reactant: C[Si](C)(C)Br
Solvent: CO
Product: CC(C)C[C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C)(NC(=O)[C@@H]3C=C4c5cccc6[nH]c(Br)c(c56)C[C@H]4N(C)C3)C(=O)N12

Procedure:
Following the process of Example 30, 1 g of ergosine is brominated with 1.4 ml of trimethylbromosilane. The title compound is isolated in a yield of 1.1 g (0.001716 mole, 94%), m.p.: 183°-185° C., [α]D20 =-91.6° (c=1, methanol).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[CH:16]=[C:15]([C:17]([F:20])([F:19])[F:18])[N:14]3[N:21]=[C:22]([C:24]4[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH:26]([CH3:37])[CH:25]=4)[CH:23]=[C:13]3[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[H][H].C1(C)C=CC=CC=1>CO.[Pd]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]2[CH2:16][CH:15]([C:17]([F:20])([F:18])[F:19])[N:14]3[N:21]=[C:22]([CH:24]4[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH:26]([CH3:37])[CH2:25]4)[CH:23]=[C:13]3[NH:12]2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]
Reactant: COc1ccc(-c2cc(C(F)(F)F)n3nc(C4=CC(C)N(C(=O)OC(C)(C)C)CC4)cc3n2)cc1OC
Reactant: [H][H]
Agent: [Pd]
Solvent: Cc1ccccc1
Solvent: CO
Product: COc1ccc(C2CC(C(F)(F)F)n3nc(C4CCN(C(=O)OC(C)(C)C)C(C)C4)cc3N2)cc1OC
Yield: 59.5 %

Procedure:
Tert-butyl 4-(5-(3,4-dimethoxyphenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-2-yl)-2-methyl-5,6-dihydropyridine-1 (2H)— carboxylate (Mixture with regioisomer tert-butyl 4-(5-(3,4-dimethoxyphenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-2-yl)-6-methyl-5,6-dihydropyridine-1(2H)-carboxylate, total is 60 mg, 0.116 mmol) was dissolved in Methanol (2.5 ml). The solution was treated with Hydrogen for 2.5 hrs at room temperature using H-Cube (Full H2, 1 mL/min, small size (30 mm) 10% Palladium on Carbon CatCart). 1 mL Toluene was added. Solvent was concentrated. The crude product was purified on silica-gel (Column Interchim 25 g, 30 μM) eluting with 12-100% EtOAc/Heptane to afford tert-butyl 4-(5-(3,4-dimethoxyphenyl)-7-(trifluoromethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-2-yl)-2-methylpiperidine-1-carboxylate (36 mg, 0.069 mmol, 59% yield) as a white solid.
Reaction SMILES: [CH:1]1([NH:5][C:6]2[C:7]3[CH:34]=[CH:33][NH:32][C:8]=3[N:9]=[C:10]([NH:12][C:13]3[CH:18]=[CH:17][C:16]([S:19]([N:22]([CH2:24][C:25]([O:27]CCCC)=[O:26])[CH3:23])(=[O:21])=[O:20])=[CH:15][CH:14]=3)[N:11]=2)[CH2:4][CH2:3][CH2:2]1.[OH-].[Na+].CC(O)=O.O>CO>[CH:1]1([NH:5][C:6]2[C:7]3[CH:34]=[CH:33][NH:32][C:8]=3[N:9]=[C:10]([NH:12][C:13]3[CH:18]=[CH:17][C:16]([S:19]([N:22]([CH2:24][C:25]([OH:27])=[O:26])[CH3:23])(=[O:20])=[O:21])=[CH:15][CH:14]=3)[N:11]=2)[CH2:4][CH2:3][CH2:2]1
Reactant: CCCCOC(=O)CN(C)S(=O)(=O)c1ccc(Nc2nc(NC3CCC3)c3cc[nH]c3n2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC(=O)O
Solvent: CO
Product: CN(CC(=O)O)S(=O)(=O)c1ccc(Nc2nc(NC3CCC3)c3cc[nH]c3n2)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 22.5 %

Procedure:
To a solution of butyl 2-(4-(4-(cyclobutylamino)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)-N-methylphenylsulfonamido)acetate (15 mg, 0.031 mmol) in MeOH (2 mL), aqueous 1N NaOH (1.00 mL, 1.00 mmol) was added. The mixture was stirred at room temperature for 3 h. Glacial HOAc (0.20 mL) was added to neutralize NaOH. When water was added, precipitate came out, which was collected by filtration to give the titled compound (3 mg). MS 431.0 (M+H); UV 206.1, 312.7 nm.
Reaction SMILES: N#N.C([Si](C)(C)[O:8][CH:9]([C:11]1[O:12][C:13]([CH2:16][N:17]2[CH:21]=[CH:20][C:19]([NH:22][C:23]([C:25]3[N:26]=[CH:27][O:28][C:29]=3[C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[O:24])=[N:18]2)=[CH:14][N:15]=1)[CH3:10])(C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.CC(=O)OCC>[OH:8][CH:9]([C:11]1[O:12][C:13]([CH2:16][N:17]2[CH:21]=[CH:20][C:19]([NH:22][C:23]([C:25]3[N:26]=[CH:27][O:28][C:29]=3[C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[O:24])=[N:18]2)=[CH:14][N:15]=1)[CH3:10]
Reactant: CC(O[Si](C)(C)C(C)(C)C)c1ncc(Cn2ccc(NC(=O)c3ncoc3-c3ccccc3)n2)o1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: N#N
Agent: [F-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(O)c1ncc(Cn2ccc(NC(=O)c3ncoc3-c3ccccc3)n2)o1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of 5-phenyl-oxazole-4-carboxylic acid (1-{2-[1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-oxazol-5-ylmethyl}-1H-pyrazol-3-yl)-amide (271 mg, 0.55 mmol) in dry THF (5.5 mL) was treated at 0° C. with TBAF (1.1 mL of a 1M solution in THF, 1.1 mmol). The reaction mixture was stirred at 0° C. for 30 min. The mixture was then diluted with EA (10 mL), washed with NaHCO3 (10 mL) followed by brine (3×10 mL), dried over MgSO4, filtered and concentrated under reduced pressure. Purification of the residue by FC (EA) gave the title compound as a white foam. TLC: rf (EA)=0.18. LC-MS-conditions 02: tR=0.87 min; [M+H]+=380.34.
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@@H:18]([O:19][C:20](=[O:22])[CH3:21])[C@H:17]([O:23][C:24](=[O:26])[CH3:25])[CH2:16][S:15][C@H:6]1[O:7][C:8]1[CH:9]=[N:10][CH:11]=[C:12](Br)[CH:13]=1)(=[O:3])[CH3:2].[Cl:27][C:28]1[CH:33]=[C:32](B(O)O)[CH:31]=[CH:30][N:29]=1>>[C:1]([O:4][C@@H:5]1[C@@H:18]([O:19][C:20](=[O:22])[CH3:21])[C@H:17]([O:23][C:24](=[O:26])[CH3:25])[CH2:16][S:15][C@H:6]1[O:7][C:8]1[CH:9]=[N:10][CH:11]=[C:12]([C:32]2[CH:31]=[CH:30][N:29]=[C:28]([Cl:27])[CH:33]=2)[CH:13]=1)(=[O:3])[CH3:2]
Reactant: OB(O)c1ccnc(Cl)c1
Reactant: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@H](OC(C)=O)CS[C@H]1Oc1cncc(Br)c1
Product: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@H](OC(C)=O)CS[C@H]1Oc1cncc(-c2ccnc(Cl)c2)c1

Procedure:
By carrying out the operation analogously to example 1, starting from 5-bromo-3-pyridinyl 2,3,4-tri-O-acetyl-5-thio-β-D-xylopyranoside, obtained according to preparation IX, and 2-chloro-4-pyridineboronic acid, the desired product is obtained in the form of an ecru solid (yield=55%).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([CH3:13])=[N:10][C:9]=2[C:14]([N:16]2[CH2:20][CH:19]3[CH2:21][CH2:22][CH2:23][CH:18]3[CH:17]2[CH2:24][N:25]2C(=O)C3C(=CC=CC=3)C2=O)=[O:15])=[CH:4][CH:3]=1.O.NN>CO>[NH2:25][CH2:24][CH:17]1[CH:18]2[CH2:23][CH2:22][CH2:21][CH:19]2[CH2:20][N:16]1[C:14]([C:9]1[N:10]=[C:11]([CH3:13])[S:12][C:8]=1[C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=1)=[O:15]
Reactant: Cc1nc(C(=O)N2CC3CCCC3C2CN2C(=O)c3ccccc3C2=O)c(-c2ccc(F)cc2)s1
Agent: NN
Solvent: O
Solvent: CO
Product: Cc1nc(C(=O)N2CC3CCCC3C2CN)c(-c2ccc(F)cc2)s1

Procedure:
2-((-2-(5-(4-Fluorophenyl)-2-methylthiazole-4-carbonyl)octahydrocyclopenta[c]pyrrol-1-yl)methyl)isoindoline-1,3-dione (1 eq) and hydrazine monohydrate (4 eq) in MeOH was stirred at 70° C. for 3 h and then concentrated in vacuo to a yellow oil. The reaction mixture was diluted with EtOAc and washed with water, brine, dried (MgSO4), and concentrated. The crude residue was purified by chromatography on silica gel (20% MeOH in EtOAc) to firstly remove the impurities and then (2:8:1 MeOH/EtOAc/TEA) to elute the title compound which was concentrated to yield a yellow oil. MS (ESI) 360.3 (M+H).
Reaction SMILES: Cl[O-].[Na+].[OH-].[Na+].[C:6]([C:9]1[CH:18]=[CH:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14]([Br:19])[CH:15]=2)[CH:10]=1)(=[O:8])C.CC1(C)CC=C(C2C=CC(C)=CC=2)C2C=C(C#CC3C=CC(C(OCC)=[O:45])=CC=3)C=CC1=2>O.O1CCOCC1>[Br:19][C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][CH:13]=1)[CH:10]=[C:9]([C:6]([OH:8])=[O:45])[CH:18]=[CH:17]2
Reactant: CC(=O)c1ccc2cc(Br)ccc2c1
Reactant: CCOC(=O)c1ccc(C#Cc2ccc3c(c2)C(c2ccc(C)cc2)=CCC3(C)C)cc1
Agent: [Na+]
Agent: [O-]Cl
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Product: O=C(O)c1ccc2cc(Br)ccc2c1
Temperature: 70 °C
Yield: 232.7 %

Procedure:
To a solution of sodium hypochlorite (62 ml, 5.25% in water (w/w), 3.6 g, 48.18 mmol) and sodium hydroxide (6.4 g, 160.6 mmol) in 50 ml of water was added a solution of 2-acetyl-6-bromonaphthalene (Compound L) 4 g, (1 6.06 mmol) in 50 ml of 1,4-dioxane. The yellow solution was heated to 70° C. in an oil bath for 2 hours, cooled to ambient temperature, and extracted with ethyl ether (2×50 ml). The aqueous layers were diluted with NaHSO3 solution (until KI indicator solution remained colorless) and then acidified (pH <2) with 1N sulfuric acid to give a white precipitate. The mixture was extracted with ethyl ether, and the combined organic phase washed with saturated aqueous NaCl, dried (MgSO4) and concentrated to give 3.54 g (88%) of the title compound as a solid. 1H NMR (DMSO-d6): δ8.63 (1H, br s), 8.32 (1H, d, J=2.0 Hz), 8.10 (1H, d, J=8.8 Hz), 8.00-8.05 (2H, m), 7.74 (1H, dd, J=2.0, 8.8 Hz).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([C:10]2[C:11]3[C:18]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:17][NH:16][C:12]=3[N:13]=[CH:14][N:15]=2)[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].[H-].[Na+].[CH3:26][Si:27]([CH2:30][CH2:31][O:32][CH2:33]Cl)([CH3:29])[CH3:28]>C1COCC1>[N+:1]([C:4]1[CH:5]=[C:6]([C:10]2[C:11]3[C:18]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:17][N:16]([CH2:33][O:32][CH2:31][CH2:30][Si:27]([CH3:29])([CH3:28])[CH3:26])[C:12]=3[N:13]=[CH:14][N:15]=2)[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2]
Reactant: CCOC(=O)c1c[nH]c2ncnc(-c3cccc([N+](=O)[O-])c3)c12
Reactant: C[Si](C)(C)CCOCCl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCOC(=O)c1cn(COCC[Si](C)(C)C)c2ncnc(-c3cccc([N+](=O)[O-])c3)c12
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of ethyl 4-(3-nitrophenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate (2.0 g, 6.4 mmol) in THF (30 mL), was added sodium hydride (180 mg, 7.50 mmol) at 0° C. The reaction was stirred for 1 hour at room temperature, then cooled back to 0° C., followed by the dropwise addition of SEMCl (1.28 g, 7.68 mmol). The solution was stirred for 4 hours at room temperature before being quenched by addition of 50 mL of a water/ice mixture. The resulting mixture was concentrated in vacuo, and the resulting solution was extracted with ethyl acetate (×3). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The reaction was then purified by chromatography using silica gel, eluting with 1-50% EtOAc/petroleum ether. The product was collected and concentrated in vacuo to afford ethyl 4-(3-nitrophenyl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate as a yellow oil. LRMS (ESI) calc'd for C21H27N4O5Si [M+H]+: 443, found 443.
Reaction SMILES: Br[C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][N:8]([C:12]3[CH:17]=[C:16]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)[N:15]=[C:14]([NH2:25])[N:13]=3)[CH2:9]2)=[CH:4][CH:3]=1.Cl.[CH3:27][N:28]1[CH:33]=[CH:32][C:31]([C:34]2[CH2:35][CH2:36][NH:37][CH2:38][CH:39]=2)=[CH:30][C:29]1=[O:40]>>[NH2:25][C:14]1[N:13]=[C:12]([N:8]2[CH2:7][CH2:6][C:5]3[C:10](=[CH:11][C:2]([N:37]4[CH2:36][CH2:35][CH:34]([C:31]5[CH:32]=[CH:33][N:28]([CH3:27])[C:29](=[O:40])[CH:30]=5)[CH2:39][CH2:38]4)=[CH:3][CH:4]=3)[CH2:9]2)[CH:17]=[C:16]([N:18]2[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]2)[N:15]=1
Reactant: Cn1ccc(C2=CCNCC2)cc1=O
Reactant: CN1CCN(c2cc(N3CCc4ccc(Br)cc4C3)nc(N)n2)CC1
Agent: Cl
Product: CN1CCN(c2cc(N3CCc4ccc(N5CCC(c6ccn(C)c(=O)c6)CC5)cc4C3)nc(N)n2)CC1

Procedure:
This compound was prepared by using procedures analogous to those described for the synthesis of Example 36 starting from 4-(7-bromo-3,4-dihydroisoquinolin-2(1H)-yl)-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine and 1-methyl-4-(1,2,3,6-tetrahydropyridin-4-yl)pyridin-2(1H)-one hydrochloride. LCMS (M+H)+: m/z=515.3.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][C:12]([C:14]([F:17])([F:16])[F:15])=[CH:13][C:8]=2[NH:7][C:6]1=[O:18].Cl.[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]([CH:29]2[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)=[O:28])=[CH:23][CH:22]=1.C(=O)([O-])[O-].[Na+].[Na+].[I-].[K+]>CC(C)CC(=O)C>[F:20][C:21]1[CH:22]=[CH:23][C:24]([C:27]([CH:29]2[CH2:34][CH2:33][N:32]([CH2:2][CH2:3][CH2:4][N:5]3[C:9]4[CH:10]=[CH:11][C:12]([C:14]([F:17])([F:16])[F:15])=[CH:13][C:8]=4[NH:7][C:6]3=[O:18])[CH2:31][CH2:30]2)=[O:28])=[CH:25][CH:26]=1
Reactant: O=c1[nH]c2cc(C(F)(F)F)ccc2n1CCCCl
Reactant: O=C(c1ccc(F)cc1)C1CCNCC1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [I-]
Solvent: CC(=O)CC(C)C
Product: O=C(c1ccc(F)cc1)C1CCN(CCCn2c(=O)[nH]c3cc(C(F)(F)F)ccc32)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 20 %

Procedure:
A mixture of 4.2 parts of 1-(3-chloropropyl)-1,3-dihydro-5-(trifluoromethyl)-2H-benzimidazol-2-one, 3.6 parts of (4-fluorophenyl) (4-piperidinyl) methanone hydrochloride, 10 parts of sodium carbonate, 0.1 parts of potassium iodide and 80 parts of 4-methyl-2-pentanone is stirred and heated till reflux. Refluxing is continued overnight. After cooling to room temperature, the reaction mixture is poured onto water. The organic phase is separated, dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and 10% of methanol as eluent. The pure fractions are collected and the eluent is evaporated. The residue is crystallized from a mixture of 4-methyl-2-pentanone and 2,2-oxybispropane, yielding 1.4 -parts (20%) of 1-{3-[4-(4-fluorobenzoyl)-1-piperidinyl]propyl}-1,3-dihydro-5-(trifluoromethyl)-2H-benzimidazol-2-one; mp. 160.2° C.
Reaction SMILES: C(OC(N(C(OC(C)(C)C)=O)C1C(C(OC)=O)=C2C(C3C=COC=3CO2)=CC=1)=O)(C)(C)C.[C:33]1([S:39]([CH2:42][C:43]2[C:48]([C:49]([O:51][CH3:52])=[O:50])=[C:47]([OH:53])[C:46]([C:54]3[CH:58]=[CH:57][O:56][C:55]=3[CH2:59][CH2:60]O)=[CH:45][CH:44]=2)(=[O:41])=[O:40])[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>>[C:33]1([S:39]([CH2:42][C:43]2[CH:44]=[CH:45][C:46]3[C:54]4[CH:58]=[CH:57][O:56][C:55]=4[CH2:59][CH2:60][O:53][C:47]=3[C:48]=2[C:49]([O:51][CH3:52])=[O:50])(=[O:41])=[O:40])[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1
Reactant: COC(=O)c1c(CS(=O)(=O)c2ccccc2)ccc(-c2ccoc2CCO)c1O
Agent: COC(=O)c1c(N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)ccc2c1OCc1occc1-2
Product: COC(=O)c1c(CS(=O)(=O)c2ccccc2)ccc2c1OCCc1occc1-2

Procedure:
Prepared by proceeding in a similar manner to Intermediate 10, starting from methyl 6-(benzenesulfonylmethyl)-2-hydroxy-3-[2-(2-hydroxyethyl)-furan-3-yl]-benzoate (Intermediate 23).
Reaction SMILES: [N+:1]([C:4]1[CH:19]=[CH:18][C:7]2[N:8]=[C:9](SC)[C:10]3[C:11](=[CH:13][S:14][CH:15]=3)[NH:12][C:6]=2[CH:5]=1)([O-:3])=[O:2].O.[CH2:21]([N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C(O)(=O)C>[N+:1]([C:4]1[CH:19]=[CH:18][C:7]2[N:8]=[C:9]([N:31]3[CH2:32][CH2:33][N:28]([CH2:21][C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=4)[CH2:29][CH2:30]3)[C:10]3[C:11](=[CH:13][S:14][CH:15]=3)[NH:12][C:6]=2[CH:5]=1)([O-:3])=[O:2]
Reactant: c1ccc(CN2CCNCC2)cc1
Reactant: CSC1=Nc2ccc([N+](=O)[O-])cc2Nc2cscc21
Solvent: CC(=O)O
Solvent: O
Product: O=[N+]([O-])c1ccc2c(c1)Nc1cscc1C(N1CCN(Cc3ccccc3)CC1)=N2

Procedure:
A solution of 6-nitro-10-(methylthio)-4H-thieno[3,4-b][1,5]benzodiazepine in excess N-benzylpiperazine and glacial acetic acid is heated at 140°-160° C. for 2 days. The solution is poured into water and the product is collected.