Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:13]3[CH:18]=[CH:17][C:16]([CH3:19])=[C:15]([CH3:20])[CH:14]=3)(O)[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.C([SiH](CC)CC)C.FC(F)(F)C(O)=O.C(=O)([O-])[O-].[Na+].[Na+]>C(OCC)(=O)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]([C:13]3[CH:18]=[CH:17][C:16]([CH3:19])=[C:15]([CH3:20])[CH:14]=3)[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1
Reactant: Cc1ccc(C2(O)C(=O)Nc3cc(Cl)ccc32)cc1C
Agent: CC[SiH](CC)CC
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O=C(O)C(F)(F)F
Product: Cc1ccc(C2C(=O)Nc3cc(Cl)ccc32)cc1C
Temperature: 80 °C
Reaction time: 0.5 h

Procedure:
Crude rac-6-chloro-3-(3,4-dimethyl-phenyl)-3-hydroxy-1,3-dihydro-indol-2-one (0.25 g, 0.87 mmol) (from Example 52a supra) was suspended in a mixture of triethylsilane (0.41 mL, 2.61 mmol) (Aldrich) and trifluoroacetic acid (1.48 g, 13.1 mmol) and heated in an 80° C. oil bath for 17 hours. After cooling to room temperature, mixture was diluted with ethyl acetate and treated with solid sodium carbonate (1 g). After stirring for 30 minutes, mixture was extracted with water and brine. Aqueous layers were back washed with ethyl acetate. Organic layers were combined, dried (Na2SO4), filtered and concentrated. Residue was recrystallized from dichloromethane-hexanes to give rac-6-chloro-3-(3,4-dimethyl-phenyl)-1,3-dihydro-indol-2-one as a brown solid. (Yield 0.18 g, 78%)
Reaction SMILES: [NH2:1][C:2]1[NH:11][C:10](=[O:12])[C:9]2[N:8]=[C:7]([CH2:13][O:14][CH3:15])[C:6]([CH3:17])([CH3:16])[NH:5][C:4]=2[N:3]=1.[ClH:18]>[Pt]=O>[ClH:18].[NH2:1][C:2]1[NH:11][C:10](=[O:12])[C:9]2[NH:8][CH:7]([CH2:13][O:14][CH3:15])[C:6]([CH3:17])([CH3:16])[NH:5][C:4]=2[N:3]=1
Reactant: COCC1=Nc2c(nc(N)[nH]c2=O)NC1(C)C
Agent: O=[Pt]
Agent: Cl
Product: COCC1Nc2c(nc(N)[nH]c2=O)NC1(C)C

Procedure:
A mixture of 2-amino-7,8-dihydro-6-methoxymethyl-7,7-dimethyl-4(3H)-pteridinone, 0.10 g and platinum oxide (prereduced) 0.015 g, in 6 mL of 2N HCl was hydrogenated at 1 atm H2 at room temperature for 2.5 hr. the mixture was filtered, and the filtrate was evaporated. This crude product was recrystallized from 6N HCl/MeCN to yield 2-amino-5,6,7,8-tetrahydro-6-methoxymethyl-7,7-dimethyl-4(3H)-pteridinone hydrochloride 0.089 g as a white solid, m.p. 214°-300° C. (dec), 76% of theoretical yield.
Reaction SMILES: O[CH2:2][C:3]1[CH2:19][N:6]2[CH:7]=[CH:8][C:9]3[C:10]([CH:11]=[C:12]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[N:13]=3)=[C:5]2[N:4]=1.O=S(Cl)[Cl:22].C(N(CC)CC)C>C(Cl)Cl>[Cl:22][CH2:2][C:3]1[CH2:19][N:6]2[CH:7]=[CH:8][C:9]3[C:10]([CH:11]=[C:12]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[N:13]=3)=[C:5]2[N:4]=1
Reactant: CCOC(=O)c1cc2c3n(ccc-2n1)CC(CO)=N3
Reactant: O=S(Cl)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCOC(=O)c1cc2c3n(ccc-2n1)CC(CCl)=N3
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 52 %

Procedure:
To a solution of 11 (47 mg, 0.18 mmol) in dry methylene chloride (10 mL), under argon, were added SOCl2 (15 μl, 0.21 mmol) and triethylamine (29 μl, 0.21 mmol). The solution was stirred at room temperature for 45 min then the solvent was removed in vacuo. The crude product was purified by chromatography using CH2Cl2/EtOH (97/3, v/v) as eluent to give compound 12 (26 mg, 52%); mp 270-272° C.; IR (KBr) 1701, 1248, 1189 cm−1; 1H NMR (400 MHz, (acetone-d6) δ 1.41 (t, 3H, J=7 Hz), 4.41 (q, 2H, J=7 Hz), 4.86 (s, 2H), 7.20 (d, 1H, J=7 Hz), 7.52 (s, 1H), 7.90 (s, 1H), 8.28 (d, 1H, J=7 Hz), 11.63 (brs, 1H); 13C NMR (100 MHz, (acetone-d6) δ 14.7, 40.6, 61.3, 102.9, 107.9, 113.1, 114.7, 125.0, 127.5, 134.3, 140.9, 142.3, 161.5; MS m/z 279 (M++2, 9), 277 (M+, 20), 196 (43), 149 (33), 85 (63), 71 (72), 57 (100). Anal. Calcd for C13H12ClN3O2: C, 56.22; H, 4.36; N, 15.13. Found: C, 56.07; H, 4.43; N, 15.10.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:3]=1.Cl.[Cl:19][C:20]1[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][C:21]=1[NH2:22].[OH-].[Na+]>O.C(O)C>[Cl:19][C:20]1[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][C:21]=1[NH:22][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:3]=1
Reactant: COc1ccc(Cl)c(N)c1
Reactant: FC(F)(F)c1cc(Cl)nc(-c2ccccc2)n1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: COc1ccc(Cl)c(Nc2cc(C(F)(F)F)nc(-c3ccccc3)n2)c1
Temperature: 25 °C
Yield: 38.2 %

Procedure:
A mixture of 4-chloro-2-phenyl-6-(trifluoromethyl)pyrimidine (50 mg, 0.193 mmol) and 2-chloro-5-methoxyaniline hydrochloride (56 mg, 0.290 mmol) in water:ethanol (1:1, 10 ml) was refluxed for 48 h. The mixture was cooled to room temperature and then basified with aqueous 2N NaOH to pH 10–12. The resulting precipitate was filtered, washed with water, water:ethanol (2:1) and isolated as a brown solid (28 mg, 38%). 1H NMR (CDCl3): 8.50–8.47 (m, 2H), 7.99 (d, J=3.0 Hz, 1H), 7.53–7.47 (m, 3H), 7.36 (d, J=9.0 Hz, 1H), 7.29 (s, 1H), 6.91 (s, 1H), 6.71 (dd, J=3.0, 9.0 Hz, 1H), 3.88 (s, 3H).
Reaction SMILES: [C:1]([NH:4][CH2:5][CH2:6][CH2:7][C:8]([C:10]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:11]=1[CH2:12][CH2:13][C:14]([OH:16])=O)=[O:9])(=[O:3])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.[CH3:34][N:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1>O1CCCC1>[Cl:21][C:18]1[CH:19]=[CH:20][C:10]([C:8]([CH2:7][CH2:6][CH2:5][NH:4][C:1](=[O:3])[CH3:2])=[O:9])=[C:11]([CH2:12][CH2:13][C:14]([N:38]2[CH2:39][CH2:40][N:35]([CH3:34])[CH2:36][CH2:37]2)=[O:16])[CH:17]=1
Reactant: CN1CCNCC1
Reactant: CC(=O)NCCCC(=O)c1ccc(Cl)cc1CCC(=O)O
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Product: CC(=O)NCCCC(=O)c1ccc(Cl)cc1CCC(=O)N1CCN(C)CC1
Temperature: 25 °C

Procedure:
3.10 g (0.01 mol) of 2-(4-acetamidobutyryl)-5-chlorohydrocinnamic acid and 1.70 g (0.011 mol) of 1,1'-carbonyldiimidazole are stirred at room temperature for 1 hour in 30 ml of tetrahydrofuran. Then, 1.2 ml (0.011 mol) of 1-methylpiperazine are added thereto at -70° and the mixture is left to warm to room temperature overnight. After concentration of the solution, the residue is extracted first with methylene chloride/2N hydrochloric acid and then with methylene chloride/concentrated aqueous ammonia solution, dried with sodium sulfate and the solvent is distilled in a vacuum. Chromatography on silica gel with methylene chloride-methanol (20:1) and crystallization from ethyl acetate/hexane gives N-[3-[4-chloro-2-[2-[(4methyl-piperazin-1-yl)carbonyl]ethyl]-benzoyl]propyl]acetamide as white crystals with melting point 126°-128°.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[CH:7][C:4]=1[CH:5]=[O:6].[I:13]Cl.Cl>CO>[I:13][C:8]1[C:9]([O:11][CH3:12])=[CH:10][C:3]([O:2][CH3:1])=[C:4]([CH:7]=1)[CH:5]=[O:6]
Reactant: ClI
Reactant: COc1ccc(C=O)c(OC)c1
Agent: Cl
Solvent: CO
Product: COc1cc(OC)c(C=O)cc1I

Procedure:
Ex-35B: To a solution of 2.4-dimethoxybenzaldehye (20.0 g, 120.4 mmol) in methanol (550 mL) was added iodine monochloride (23.5 g in 60 mL methanol) dropwise over 20 min at ambient temperature. The solution was allowed to stir at this temperature. HPLC showed about 94% conversion after 3 hours. The reaction mixture was then poured into a solution of HCl (0.5M, 600 mL). The precipitate was collected by filtration, washed with water, dried in vacuo (40° C.) to give crude product of 33.02 g. The crude product was further purified by recrystallization from THF/heptane (1:1) to give 5-iodo-2,4-dimethoxybenzaldehyde as an off-white solid (27.5 g, m.p 170–172° C.). The mother liquid was concentrated to dryness. The residual material was dissolved in EtOH (100 mL) and acetone (20 mL) followed by addition of water (20 mL) to give additional product (3.12 g, m.p. 169–171° C.). Overall isolated yield of this reaction was 87.5%. 1H NMR (CDCl3) δ 10.20 (s, 1H), 8.22 (s, 1H), 6.39 (s, 1H), 3.97 (s, 3H), 3.95 (s, 3H). HRMS Calcd. for C9H9IO3: 291.9596 (M+); Found: 291.9602. Anal. Calcd. for C8H9NO3S: C, 37.01; H, 3.11; 1, 43.33; Found: C, 37.12; H, 3.15; I, 43.33.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[CH2:7][CH2:6]2.[H-].[Na+].Br[CH2:16][CH2:17][CH:18]=[CH2:19]>CN(C=O)C.C(Cl)Cl>[CH2:16]([C:7]1([CH2:10][CH2:11][CH:3]=[CH2:4])[CH2:6][C:5]2[C:9](=[CH:10][CH:11]=[C:3]([O:2][CH3:1])[CH:4]=2)[C:8]1=[O:12])[CH2:17][CH:18]=[CH2:19]
Reactant: COc1ccc2c(c1)CCC2=O
Reactant: C=CCCBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: ClCCl
Product: C=CCCC1(CCC=C)Cc2cc(OC)ccc2C1=O
Reaction time: 20 h

Procedure:
To a solution of 5-methoxy-1-indanone (1 g, 6.17 mmol) in DMF (6 mL) at rt was added NaH (740 mg, 61% in oil, 18.5 mmol) and 4-bromo-1-butene (2.5 mL, 24.7 mmol). After 20 h at rt, the solution was diluted with CH2Cl2 and quenched with saturated aqueous NH4Cl. The slurry was dried with MgSO4 and filtered through a plug of silica and rinsed with 10% EtOAc in hexanes. The filtrate was concentrated and provided crude 2,2-di(3-butenyl)-5-methoxy-1-indanone.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]2[CH2:14][CH2:13][CH2:12][C:11](=O)[CH:10]=2)[CH:6]=[CH:7][CH:8]=1.[BH4-].[Na+].C[O:19][C:20](OC)([N:22]([CH3:24])[CH3:23])[CH3:21]>C1(C)C(C)=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]2([CH2:21][C:20]([N:22]([CH3:24])[CH3:23])=[O:19])[CH2:14][CH2:13][CH:12]=[CH:11][CH2:10]2)[CH:6]=[CH:7][CH:8]=1
Reactant: COc1cccc(C2=CC(=O)CCC2)c1
Reactant: COC(C)(OC)N(C)C
Agent: [BH4-]
Agent: [Na+]
Solvent: Cc1ccccc1C
Product: COc1cccc(C2(CC(=O)N(C)C)CC=CCC2)c1

Procedure:
10 g of 3-(m-methoxyphenyl)-2-cyclohexen-1-ol obtained by reducing 3-(m-methoxyphenyl)-2-cyclohexen-1-one with sodium borohydride, are dissolved in 100 ml of xylene, whereupon 12 g of N,N-dimethylacetamide dimethyl acetal are added, and the mixture is boiled at reflux for 8 hours. After distillation of the solvent, the oil remaining behind is chromatographed on a 30-fold amount of silica gel. The fractions which are uniform in accordance with thin-layer chromatography and which are produced by elution with methylene chloride, are combined and evaporated, and there is obtained pure 1-(m-methoxyphenyl)-N,N-dimethyl-3-cyclohexene-1-acetamide in the form of a pale yellowish oil.
Reaction SMILES: I[C:2]1[CH:3]=[N:4][N:5]2[C:10]([C:11]([F:14])([F:13])[F:12])=[CH:9][C:8]([C:15]3[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=3)=[N:7][C:6]=12.[C:25]1([C:31]#[CH:32])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>>[C:25]1([C:31]#[C:32][C:2]2[CH:3]=[N:4][N:5]3[C:10]([C:11]([F:14])([F:13])[F:12])=[CH:9][C:8]([C:15]4[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=4)=[N:7][C:6]=23)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: FC(F)(F)c1ccc(-c2cc(C(F)(F)F)n3ncc(I)c3n2)cc1
Reactant: C#Cc1ccccc1
Product: FC(F)(F)c1ccc(-c2cc(C(F)(F)F)n3ncc(C#Cc4ccccc4)c3n2)cc1

Procedure:
The title compound was prepared from 3-Iodo-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine (example C.1, method 2, step 2) (340 mg, 1.0 mmol) and phenylacetylene (267 mg, 1.0 mmol) according to general procedure II. Obtained as an orange solid (250 mg, 58%). MS (ISP) 432.3[(M+H)+]; mp 144–145° C.
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].CS(C)=O.Br[C:17]1[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:18]=1[C:19]([O:21][CH3:22])=[O:20]>C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].[Cu]>[F:27][C:25]1[CH:24]=[C:23]([C:2]2[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=2[N+:9]([O-:11])=[O:10])[C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:17][CH:26]=1
Reactant: COC(=O)c1ccc(F)cc1Br
Reactant: O=[N+]([O-])c1ccc(F)cc1Br
Agent: [Cu]
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: CCOC(C)=O
Solvent: CS(C)=O
Product: COC(=O)c1ccc(F)cc1-c1cc(F)ccc1[N+](=O)[O-]
Temperature: 100 °C
Reaction time: 2 h
Yield: 113.3 %

Procedure:
To 2-bromo-4-fluoro-1-nitrobenzene (185.16 mg, 0.842 mmol) was added Pd2dba3 (23.12 mg, 0.025 mmol) and copper powder (271 mg, 4.26 mmol). Dimethylsulfoxide (2.3 ml) and methyl 2-bromo-4-fluorobenzoate (0.122 ml, 0.842 mmol) were added and the mixture was stirred vigorously at 100° C. for 2 h. The mixture was cooled to room temperature, diluted with ethyl acetate (20 ml), and filtered. The filtrate was washed with water and dried (anhydrous Na2SO4) and concentrated to give a yellow oil (279.8 mg). This oil was utilized without purification for the preparation of Example 38b.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[CH:4][N:3]=1.[F:9][C:10]1[CH:11]=[C:12]([NH:17][C:18](=[O:20])[CH3:19])[CH:13]=[CH:14][C:15]=1[OH:16].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[Cl:8][C:6]1[N:5]=[CH:4][N:3]=[C:2]([O:16][C:15]2[CH:14]=[CH:13][C:12]([NH:17][C:18](=[O:20])[CH3:19])=[CH:11][C:10]=2[F:9])[CH:7]=1
Reactant: Clc1cc(Cl)ncn1
Reactant: CC(=O)Nc1ccc(O)c(F)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(=O)Nc1ccc(Oc2cc(Cl)ncn2)c(F)c1
Temperature: 70 °C
Yield: 71 %

Procedure:
A mixture of 4,6-dichloropyrimidine (1.50 g, 10.0 mmol), N-(3-fluoro-4-hydroxyphenyl)acetamide (1.70 g, 10.0 mmol), K2CO3 (1.8 g, 13.0 mmol), and DMF (15 mL) was heated at 70° C. for 1.5 h. The mixture was concentrated to half its original volume and cooled in an ice bath. The mixture was treated with H2O (100 mL) to precipitate the product which was collected by vacuum filtration. The product was washed with H2O and vacuum dried on the funnel overnight to give the title compound (2.0 g, 71%) as a gray solid. 1H NMR (DMSO-d6) δ 10.26 (s, 1H), 8.67 (s, 1H), 7.78 (dd, 1H, J=12.6, 2.0 Hz), 7.56 (s, 1H), 7.37-7.30 (m, 2H), 2.08 (s, 3H); MS (ESI+) m/z 282.10 (M+H)+.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([F:25])=[C:21]([F:26])[CH:20]=2)=[C:6]([CH:16]=1)[C:7]([NH:9][C:10]1[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=1)=[O:8].[CH3:27][N:28]1[CH:32]=[C:31](B2OC(C)(C)C(C)(C)O2)[CH:30]=[N:29]1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.COCCOC>[F:26][C:21]1[CH:20]=[C:19]([CH2:18][O:17][C:5]2[CH:4]=[CH:3][C:2]([C:31]3[CH:30]=[N:29][N:28]([CH3:27])[CH:32]=3)=[CH:16][C:6]=2[C:7]([NH:9][C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)=[O:8])[CH:24]=[CH:23][C:22]=1[F:25]
Reactant: O=C(Nc1cccnc1)c1cc(Br)ccc1OCc1ccc(F)c(F)c1
Reactant: Cn1cc(B2OC(C)(C)C(C)(C)O2)cn1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Product: Cn1cc(-c2ccc(OCc3ccc(F)c(F)c3)c(C(=O)Nc3cccnc3)c2)cn1
Temperature: 120 °C

Procedure:
To a microwave vial was added 5-bromo-2-([(3,4-difluorophenyl)methyl]oxy}-N-3-pyridinylbenzamide (may be prepared as described in Example 60; 120 mg, 0.29 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (65.5 mg, 0.32 mmol), 1,2-dimethoxyethane (2 ml), 1M sodium carbonate (0.57 ml, 0.57 mmol) and tetrakis(triphenylphosphine)palladium(0) (19.85 mg, 0.017 mmol). The vial was sealed and heated to 120° C. for 1 hr under microwave conditions. The mixture was evaporated under reduced pressure. Water (5 ml) was added to the residue and the mixture was extracted with ethyl acetate (3×10 ml). The organics were combined, evaporated under reduced pressure and the residue was purified using the MDAP to yield the title compound. 28 mg.
Reaction SMILES: [CH3:1][C:2]1([CH3:22])[CH2:7][N:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N+:9]=2[O-:14])[C:5]2[CH:15]=[CH:16][C:17]([N+:19]([O-])=O)=[CH:18][C:4]=2[O:3]1.[Cl-].[NH4+].CO>[Zn].O>[NH2:19][C:17]1[CH:16]=[CH:15][C:5]2[N:6]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][N+:9]=3[O-:14])[CH2:7][C:2]([CH3:22])([CH3:1])[O:3][C:4]=2[CH:18]=1
Reactant: CC1(C)CN(c2cccc[n+]2[O-])c2ccc([N+](=O)[O-])cc2O1
Agent: [Cl-]
Agent: [NH4+]
Agent: [Zn]
Solvent: CO
Solvent: O
Product: CC1(C)CN(c2cccc[n+]2[O-])c2ccc(N)cc2O1
Temperature: 5 °C
Reaction time: 14 h
Yield: 101 %

Procedure:
To a mixture of 8.05 g 2-(3,4-dihydro-2,2-dimethyl-7-nitro-2H-1,4-benzoxazin-4-yl)pyridine N-oxide, 28.50 g ammonium chloride, 140 ml methanol and 140 ml water, was added 34.94 g zinc powder under ice cooling, and the resulting mixture was stirred at 5° C. for 14 hours. The insoluble matters were filtered off from the reaction mixture, the filtrate was concentrated, the concentrate was extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate, and the solvents were distilled off form the dried solution, giving 7.32 g of crude 2-(7-amino-3,4-dihydro-2,2-dimethyl-2H-1,4-benzoxazin-4-yl)pyridine N-oxide.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[N:7]([CH2:30][CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[C:8]([C:10]1[CH:29]=[CH:28][C:13]2[N:14]([CH3:27])[C:15]([CH2:17][NH:18][C:19]3[N:24]=[CH:23][C:22]([C:25]#[N:26])=[CH:21][CH:20]=3)=[N:16][C:12]=2[CH:11]=1)=[O:9].[ClH:37].C(=O)([O-])[O-].[NH4+:42].[NH4+]>C(O)C>[ClH:37].[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[N:7]([CH2:30][CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[C:8]([C:10]1[CH:29]=[CH:28][C:13]2[N:14]([CH3:27])[C:15]([CH2:17][NH:18][C:19]3[N:24]=[CH:23][C:22]([C:25](=[NH:42])[NH2:26])=[CH:21][CH:20]=3)=[N:16][C:12]=2[CH:11]=1)=[O:9]
Reactant: [NH4+]
Reactant: CCOC(=O)CCN(C(=O)c1ccc2c(c1)nc(CNc1ccc(C#N)cn1)n2C)c1ccccn1
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: CCO
Product: CCOC(=O)CCN(C(=O)c1ccc2c(c1)nc(CNc1ccc(C(=N)N)cn1)n2C)c1ccccn1

Procedure:
Prepared analogously to Example 25d from 1-Methyl-2-[N-(3-cyanopyridin-6-yl)aminomethyl]benzimidazol-5-yl-carboxylic acid-N-(2-pyridyl)-N-(2-ethoxycarbonylethyl)amide and ethanolic hydrochloric acid, ethanol, and ammonium carbonate.
Reaction SMILES: [CH3:1][NH:2][C:3]1[N:8]=[C:7](Cl)[N:6]=[C:5]([Cl:10])[N:4]=1.[CH3:11][O:12][C:13]1[CH:14]=[C:15]([CH:17]=[C:18]([O:22][CH3:23])[C:19]=1[O:20][CH3:21])[NH2:16].C(Cl)Cl.[K+].[Br-]>>[CH3:23][O:22][C:18]1[CH:17]=[C:15]([NH:16][C:7]2[N:8]=[C:3]([NH:2][CH3:1])[N:4]=[C:5]([Cl:10])[N:6]=2)[CH:14]=[C:13]([O:12][CH3:11])[C:19]=1[O:20][CH3:21]
Reactant: CNc1nc(Cl)nc(Cl)n1
Reactant: COc1cc(N)cc(OC)c1OC
Agent: [Br-]
Agent: [K+]
Solvent: ClCCl
Product: CNc1nc(Cl)nc(Nc2cc(OC)c(OC)c(OC)c2)n1
Yield: 65 %

Procedure:
The title compound was synthesized from 2-methylamino-4,6-dichloro-1,3,5-triazine and 3,4,5-trimethoxyaniline using a similar procedure to the one used in 2. Yield: 65%; Tm 237° C.; FTIR (CH2Cl2/KBr) 3270, 3134, 3051, 2964, 2940, 2842, 2831, 1658, 1631, 1612, 1588, 1567, 1535, 1502, 1453, 1422, 1390, 1351, 1297, 1264, 1230, 1201, 1189, 1172, 1128, 1082, 1057, 1034, 997, 978, 924, 882, 830, 809, 735, 704, 679 cm−1; 1H NMR (300 MHz, DMSO-d6, 298K) δ 9.97, 9.77 (s, s, 1H), 8.09, 7.91 (s, s, 1H), 7.21, 7.09 (s, s, 2H), 3.74 (s, 6H), 3.61 (s, 3H), 2.86, 2.80 (d, d, 3J=4.6 Hz, 3H) ppm; 13C NMR (75 MHz, DMSO-d6): δ 167.4, 165.8, 165.6, 163.3, 162.9, 152.5, 135.0, 134.8, 133.2, 133.0, 98.2, 97.6, 60.0, 55.8, 55.5, 27.4, 27.2 ppm; HRMS (EI) calcd. for C13H16ClN5O3 (m/e): 325.0942. found: 325.0934.
Reaction SMILES: C([O:8][C@@H:9]1[CH2:13][CH2:12][CH2:11][C@H:10]1[NH2:14])C1C=CC=CC=1.[C:15]([OH:21])([C:17]([F:20])([F:19])[F:18])=[O:16]>CCO.[OH-].[OH-].[Pd+2]>[OH:21][C:15]([C:17]([F:20])([F:19])[F:18])=[O:16].[NH2:14][C@@H:10]1[CH2:11][CH2:12][CH2:13][C@H:9]1[OH:8]
Reactant: N[C@@H]1CCC[C@H]1OCc1ccccc1
Agent: [Pd+2]
Agent: [OH-]
Solvent: CCO
Solvent: O=C(O)C(F)(F)F
Product: N[C@@H]1CCC[C@H]1O
Temperature: 25 °C
Reaction time: 72 h

Procedure:
To a solution of (1R,2R)-2-(benzyloxy)cyclopentanamine (3.5 g, 18.3 mmol) in EtOH (20 mL) was added TFA (1.6 ml, 21.5 mmol), followed by addition of Pd(OH)2/C (20% wt, 627 mg). The reaction mixture was degassed and stirred at ambient temperature under H2 for 3 days, then the solid was removed by filtration and the residue was rinsed with EtOH. The filtrate was concentrated to yield (1R,2R)-2-aminocyclopentanol TFA salt as a yellow oil. (4.3 g, 100%). NMR: 400 MHz 1H (DMSO-D6) 7.96 ppm, 2H, m; 3.95 ppm, 1H, m; 3.17 ppm, 1H, m; 2.02 ppm, 1H, m; 1.87 ppm, 1H, m; 1.66 ppm, 2H, m; 1.48 ppm, 2H, m; 1.07 ppm, 1H, m.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][N:9]=[CH:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:4][CH:3]=1.[CH:17](O)=[O:18].C(OC(=O)C)(=O)C>COCCOC>[CH:17]([N:8]([C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=1)[N:9]=[CH:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)=[O:18]
Reactant: O=CO
Reactant: Clc1ccc(NN=Cc2ccccc2)cc1
Solvent: COCCOC
Solvent: CC(=O)OC(C)=O
Product: O=CN(N=Cc1ccccc1)c1ccc(Cl)cc1
Reaction time: 4 h

Procedure:
6.91 g of 1A was dissolved in 37.5 ml of dry 1,2-dimethoxyethane and treated with 4.5 g of distilled mixed anhydride of formic acid and acetic acid prepared by mixing the appropriate amount of formic acid and acetic anhydride. The resulting mixture was left for 4 hours at room temperature and then heated up to boiling point and excess solvent removed in vacuo. The residue was triturated with 5% sodium bicarbonate solution, dried and crystallized from methanol to give 1, mp 122°-123° C.
Reaction SMILES: [N-:1]=[N+:2]=[N-:3].[Na+].CO.[S:7](Cl)([C:10]1[CH:16]=[CH:15][C:13]([CH3:14])=[CH:12][CH:11]=1)(=[O:9])=[O:8]>O>[S:7]([N:1]=[N+:2]=[N-:3])([C:10]1[CH:16]=[CH:15][C:13]([CH3:14])=[CH:12][CH:11]=1)(=[O:9])=[O:8]
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: Cc1ccc(S(=O)(=O)N=[N+]=[N-])cc1

Procedure:
In a 250 ml round bottom flask was added 60 ml of deionized (DI) water and 21 g (0.32 mole) of sodium azide. It was mixed at room temperature for 15 minutes until all the sodium azide was in solution. In a 1 liter round bottom flask was added 300 ml of methanol and 50.1 g (0.26 moles) of toluenesulfonyl chloride(tosyl chloride). The solution was mixed at room temperature until all of the tosyl chloride was dissolved. The sodium azide solution was added to the tosyl chloride solution and mixed for 1 hour. The solution darkened and a second phase formed. After the 1 hour hold the reaction was poured into 1200 ml of 20° C. DI water. Two phases formed and the bottom layer was kept. The bottom layer was washed twice with 100 ml of DI water. The yield was 32.4 grams.
Reaction SMILES: [OH:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1.C1C=C[NH+]=CC=1.[O-][Cr](Cl)(=O)=O>C(Cl)Cl>[CH:2]([CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1)=[O:1]
Reactant: CC(C)(C)OC(=O)N1CCC(CO)CC1
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCC(C=O)CC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 42 %

Procedure:
To the solution of tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate (139.5 mmol) in DCM (300 ml) was added PCC (209.3 mmol, 1.5 eq) at 0° C. The reaction mixture was then allowed to stir at 25° C. for 16 h. The mixture was filtered through celite, washed with DCM (2×200 ml), and the organics were concentrated and purified by silica gel column chromatography (10% EtOAc in DCM) to obtain the desired compound. Yield: 42%