Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([C:13]1[N:14]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:16][CH:17]=1)[CH:7]=[CH:6]2.Cl.N1C=CC=CC=1>>[C:24]1([N:14]2[C:15]([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)=[CH:16][CH:17]=[C:13]2[C:8]2[CH:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[CH:4]=[C:3]([OH:2])[CH:12]=[CH:11]3)[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1
Reactant: COc1ccc2cc(-c3ccc(-c4ccccc4)n3-c3ccccc3)ccc2c1
Agent: Cl
Solvent: c1ccncc1
Product: Oc1ccc2cc(-c3ccc(-c4ccccc4)n3-c3ccccc3)ccc2c1
Temperature: 205 °C
Yield: 83.1 %

Procedure:
In a similar manner as described in step 5 of Example 1, the title compound was prepared from 2-(6-methoxy-2-naphthyl)-1,5-dipheny-1H-pyrrol (1.25 g, 3.33 mmol), prepared in the previous step, and pyridine hydrochloride (30 g) with the exception that this reaction required heating at 205° C. Purification on silica gel (500 g, 200–300 mesh) using methylene chloride as the eluent gave 6-(1,5-diphenyl-1H-pyrrol-2-yl)-2-naphthol as a reddish solid (1.00 g, 83%), mp 222–223° C. Elemental Analysis for C26H19NO.0.11 C4H8O2 Calc'd: C, 85.57; H, 5.40; N, 3.77. Found: C, 85.28; H, 5.53; N, 3.73.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([Cl:9])[CH:3]=1.S(C1C=CC(C)=CC=1)(O[CH2:14][CH2:15][O:16][CH2:17][CH2:18][O:19][CH3:20])(=O)=O.BrC1C=CC(OCCOCCOC)=C(C)C=1>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:14][CH2:15][O:16][CH2:17][CH2:18][O:19][CH3:20])=[C:4]([Cl:9])[CH:3]=1
Reactant: Oc1ccc(Br)cc1Cl
Reactant: COCCOCCOS(=O)(=O)c1ccc(C)cc1
Agent: COCCOCCOc1ccc(Br)cc1C
Product: COCCOCCOc1ccc(Br)cc1Cl

Procedure:
Prepared from 4-bromo-2-chlorophenol and 2-(2-methoxyethoxy)ethyl tosylate by the method of Example 42 (b).
Reaction SMILES: [CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:21])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[F:32]NS(C1C=CC=CC=1)(=O)=O>C1COCC1>[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:21])[CH:15]([F:32])[CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCCCCCC(=O)N1C(=O)OC[C@@H]1Cc1ccccc1
Reactant: O=S(=O)(NF)c1ccccc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: CCCCCC(F)C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1
Temperature: -78 °C
Reaction time: 1 h
Yield: 79.2 %

Procedure:
To a solution of (4S)-benzyl-3-heptanoyl-oxazolidin-2-one (12.0 g, 41.4 mmol) in THF (30 ml) stirred under N2 at −78° C. was added dropwise a solution of lithium bis(trimethylsilyl)amide (50 ml of 1 M soln. in THF, 50 mmol). This was stirred 1 h at −78° C. then added to solution of N-fluorobenzenesulfonamide (14.3 g, 45.5 mmol) in THF (60 ml) stirred under N2 at −78° C. The reaction mixture was stirred 2.5 h at −78° C. then quenched with aqueous amonium chloride. The product mixture was partitioned between EtOAc and water. The organic extract was washed with brine, dried and all volitiles removed. Chromatography on silica (10% EtOAc 90% hexane) afforded 10.08 g (79%) of the title compound. Mass spectrum ES+: 308 [M+H]+
Reaction SMILES: N#N.[C:3]([O:9][C:10]1([C:13]2[N:14]=[C:15]([CH2:18][N:19]3[N:23]=[C:22]([N+:24]([O-])=O)[CH:21]=[N:20]3)[O:16][CH:17]=2)[CH2:12][CH2:11]1)(=[O:8])[C:4]([CH3:7])([CH3:6])[CH3:5].[NH4+].[Cl-]>CCO.O.[Fe]>[C:3]([O:9][C:10]1([C:13]2[N:14]=[C:15]([CH2:18][N:19]3[N:23]=[C:22]([NH2:24])[CH:21]=[N:20]3)[O:16][CH:17]=2)[CH2:12][CH2:11]1)(=[O:8])[C:4]([CH3:7])([CH3:6])[CH3:5]
Reactant: CC(C)(C)C(=O)OC1(c2coc(Cn3ncc([N+](=O)[O-])n3)n2)CC1
Agent: [Fe]
Agent: N#N
Agent: [Cl-]
Solvent: CCO
Solvent: O
Product: CC(C)(C)C(=O)OC1(c2coc(Cn3ncc(N)n3)n2)CC1
Temperature: 85 °C
Reaction time: 0.25 h

Procedure:
In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a mixture of 1-(2-((4-nitro-2H-1,2,3-triazol-2-yl)methyl)oxazol-4-yl)cyclopropyl pivalate (150 mg, 0.45 mmol), iron powder (76 mg, 1.34 mmol) and NH4Cl (121 mg, 2.24 mmol) in a mixture of EtOH (2.0 mL) and water (1.0 mL) was stirred at 85° C. for 15 min. The reaction mixture was filtered while hot and concentrated under reduced pressure. CH2Cl2 (5.0 mL) was added followed by 1N NaOH (5.0 mL). The layers were separated and the aq. layer was extracted with CH2Cl2 (2×5 mL). The combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure to give the title compound as a yellow oil. LC-MS-conditions 06: tR=0.73 min; [M+H]+=306.04.
Reaction SMILES: [OH:1][C@@H:2]1[CH2:9][N:8]([CH2:10][CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][N:16]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21](I)[CH:20]=3)[CH:15]([CH3:26])[C:14]2=[O:27])[CH2:7][CH2:6][C:3]21[CH2:5][CH2:4]2.C([Sn](CCCC)(CCCC)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=1)CCC.[Cl-].[Li+]>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.CN(C)C=O>[OH:1][C@@H:2]1[CH2:9][N:8]([CH2:10][CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][N:16]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=4)[CH:20]=3)[CH:15]([CH3:26])[C:14]2=[O:27])[CH2:7][CH2:6][C:3]21[CH2:5][CH2:4]2
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccccn1
Reactant: CC1C(=O)N(CCCN2CCC3(CC3)[C@H](O)C2)CCN1c1cccc(I)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cl-]
Agent: [Li+]
Solvent: CN(C)C=O
Product: CC1C(=O)N(CCCN2CCC3(CC3)[C@H](O)C2)CCN1c1cccc(-c2ccccn2)c1
Temperature: 100 °C
Yield: 4.7 %

Procedure:
A mixture of 1-[3-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-propyl]-4-(3-iodo-phenyl)-3-methyl-piperazin-2-one (example 89; 80 mg, 0.17 mmol), 2-(tributylstannyl)pyridine (73 mg, 0.20 mmol), tetrakis(triphenylphosphine)palladium(0), lithium chloride (42 mg, 0.99 mmol) copper chloride (82 mg, 0.83 mmol), and N,N-dimethylformamide (3 mL) was heated at 100° C. for 16 h, then the reaction mixture was partitioned between CH2Cl2 and sat. aq. NaHCO3 solution. The organic layer was washed with brine, dried (MgSO4), filtered, and evaporated. Chromatography (SiO2; EtOAc-MeOH gradient) afforded the title compound (3.5 mg, 5%). Colorless gum, MS: 435.3 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([OH:11])=[N:7][NH:8]2)=[CH:4][CH:3]=1.[CH2:12]([O:14][C:15](N1C2C(=C(Br)C=CC=2)C(O)=N1)=[O:16])[CH3:13]>>[CH2:12]([O:14][C:15]([N:8]1[C:9]2[C:5](=[CH:4][CH:3]=[C:2]([Br:1])[CH:10]=2)[C:6]([OH:11])=[N:7]1)=[O:16])[CH3:13]
Reactant: Oc1n[nH]c2cc(Br)ccc12
Reactant: CCOC(=O)n1nc(O)c2c(Br)cccc21
Product: CCOC(=O)n1nc(O)c2ccc(Br)cc21

Procedure:
6-Bromo-3-hydroxy-indazole-1-carboxylic acid ethyl ester CCXXXV was prepared from 6-bromo-1H-indazol-3-ol using the procedure described for preparation of 4-Bromo-3-hydroxy-indazole-1-carboxylic acid ethyl ester CLXXXIV (Example 37).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][C:13]2[CH:18]=[C:17]([Cl:19])[C:16]([O:20][C:21]3[C:26]([C:27]([N:29]4[C:38]5[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=5)[N:32]([CH:39]5[CH2:41][CH2:40]5)[CH2:31][CH2:30]4)=[O:28])=[CH:25][CH:24]=[CH:23][N:22]=3)=[CH:15][C:14]=2[Cl:42])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5]>C(O)C.[Pd]>[Cl:1][C:2]1[CH:10]=[C:9]([CH2:11][CH2:12][C:13]2[CH:18]=[C:17]([Cl:19])[C:16]([O:20][C:21]3[C:26]([C:27]([N:29]4[C:38]5[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=5)[N:32]([CH:39]5[CH2:41][CH2:40]5)[CH2:31][CH2:30]4)=[O:28])=[CH:25][CH:24]=[CH:23][N:22]=3)=[CH:15][C:14]=2[Cl:42])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5]
Reactant: O=C(O)c1ccc(C#Cc2cc(Cl)c(Oc3ncccc3C(=O)N3CCN(C4CC4)c4ccccc43)cc2Cl)cc1Cl
Agent: [Pd]
Solvent: CCO
Product: O=C(O)c1ccc(CCc2cc(Cl)c(Oc3ncccc3C(=O)N3CCN(C4CC4)c4ccccc43)cc2Cl)cc1Cl
Temperature: 25 °C
Yield: 100.3 %

Procedure:
To a suspension of 2-chloro-4-{2,5-dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-2-yloxy]-phenylethynyl}-benzoic acid (100 mg, 0.16 mmol, 1.0 equiv; Example 168) in ethanol (1.5 mL) was added palladium on carbon (3.2 mg, 0.003 mmol, 0.02 equiv; 10% Pd/C; [CAS RN 7440-05-3]) and the reaction mixture stirred under an atmosphere of hydrogen (3 bar) at rt over night. Removal of the solvent mixture under reduced pressure, filtration over Celite® and lyophilization from dioxane provided 100 mg (96%) of the title compound as an off-white solid. MS (ISP): 620.3 [M−H]−.
Reaction SMILES: [S:1]([C:5]1[S:9][C:8]([C:10]2[CH:18]=[CH:17][C:13]([C:14]([OH:16])=O)=[CH:12][CH:11]=2)=[CH:7][CH:6]=1)(=[O:4])(=[O:3])[NH2:2].[Li].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[NH:51]1[CH2:55][CH2:54][CH2:53][C@H:52]1[CH2:56][N:57]1[CH2:61][CH2:60][CH2:59][CH2:58]1>CN(C=O)C.ClCCl>[N:57]1([CH2:56][C@@H:52]2[CH2:53][CH2:54][CH2:55][N:51]2[C:14]([C:13]2[CH:12]=[CH:11][C:10]([C:8]3[S:9][C:5]([S:1]([NH2:2])(=[O:3])=[O:4])=[CH:6][CH:7]=3)=[CH:18][CH:17]=2)=[O:16])[CH2:61][CH2:60][CH2:59][CH2:58]1
Reactant: C1CN[C@H](CN2CCCC2)C1
Reactant: NS(=O)(=O)c1ccc(-c2ccc(C(=O)O)cc2)s1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: CN(C)C=O
Product: NS(=O)(=O)c1ccc(-c2ccc(C(=O)N3CCC[C@H]3CN3CCCC3)cc2)s1
Yield: 34 %

Procedure:
The title compound is prepared in a manner substantially analogous to General Procedure D in 9 mL 50% DMF/dichloromethane using 4-(5-Sulfamoyl-thiophen-2-yl)-benzoic acid, lithium salt (173 mg, 0.61 mmol), EDC-HCl (174 mg, 0.91 mmol), HOBt (123 mg, 0.91 mmol), DIEA (0.26 mL, 1.5 mmol) and (S)(+)-1-(2-pyrrolidinylmethyl)pyrrolidine (79 mg, 0.51 mmol) to give the title compound (74 mg, 34% yield). MS (ES+) 420.2 (M+H)+
Reaction SMILES: [O:1]1[CH:5]=[CH:4][C:3]([C:6]([NH:8][C:9]2[CH:10]=[CH:11][C:12]([CH3:24])=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([C:21]([OH:23])=O)=[CH:17][CH:16]=3)[CH:14]=2)=[O:7])=[CH:2]1.[NH2:25][CH2:26][CH2:27][CH2:28][N:29]1[CH:33]=[CH:32][N:31]=[CH:30]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C>[N:29]1([CH2:28][CH2:27][CH2:26][NH:25][C:21]([C:18]2[CH:19]=[CH:20][C:15]([C:13]3[C:12]([CH3:24])=[CH:11][CH:10]=[C:9]([NH:8][C:6]([C:3]4[CH:4]=[CH:5][O:1][CH:2]=4)=[O:7])[CH:14]=3)=[CH:16][CH:17]=2)=[O:23])[CH:33]=[CH:32][N:31]=[CH:30]1
Reactant: Cc1ccc(NC(=O)c2ccoc2)cc1-c1ccc(C(=O)O)cc1
Reactant: NCCCn1ccnc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: On1nnc2ccccc21
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: Cc1ccc(NC(=O)c2ccoc2)cc1-c1ccc(C(=O)NCCCn2ccnc2)cc1

Procedure:
5′-(3-Furoylamino)-2′-methyl-1,1′-biphenyl-4-carboxylic acid (50 mg, 0.156 mmol), 1-(3-aminopropyl)imidazole (19.5 mg, 0.156 mmol), HATU (59.2 mg, 0.156 mmol), HOBT (21 mg, 0.156 mmol) and DIPEA (27 μl, 0.156 mmol) in DMF (2 ml) were stirred at room temperature for 18 h. The reaction was diluted with ethyl acetate (150 ml), washed with water (2×30 ml) and dried (magnesium sulphate). The solvent was evaporated under vacuum and the residue chromatographed on a silica flash column eluting with DCM/methanol/triethylamine (96:2:2). Concentration of the product fractions under vacuum N-(4′-{[(3-imidazol-1-ylpropyl)amino]carbonyl}-6-methyl-1,1′-biphenyl-3-yl)-3-furamide (44.1 mg, 66%). NMR; δH [2H6]-DMSO 9.92,(1H, s), 8.58,(1H, t), 8.35,(1H, s), 7.92,(2H, d), 7.78,(1H, t), 7.67-7.65,(2H, m), 7.60,(1H, d), 7.44,(2H, d), 7.27,(1H, d), 7.22,(1H, m), 6.98,(1H, m), 6.89,(1H, m), 4.03,(2H, t), 3.26,(2H, q), 2.19,(3H, s), 1.97,(2H, m). LCMS: retention time 2.31 min, MH+429.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:34])[C:5]([NH:27][C:28]([O:30][CH2:31][CH:32]=[CH2:33])=[O:29])([CH2:9][C:10]1[O:14][N:13]=[C:12]([CH:15]2[CH2:19][CH2:18][CH2:17][N:16]2[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH:11]=1)C(O)=O)[CH3:2].C(OC(=O)C(NC(OCC=C)=O)(CC1ON=C(C2CCCN2C(OC(C)(C)C)=O)C=1)C(OCC)=O)C>O1CCOCC1>[C:23]([O:22][C:20]([N:16]1[CH2:17][CH2:18][CH2:19][CH:15]1[C:12]1[CH:11]=[C:10]([CH2:9][CH:5]([NH:27][C:28]([O:30][CH2:31][CH:32]=[CH2:33])=[O:29])[C:4]([O:3][CH2:1][CH3:2])=[O:34])[O:14][N:13]=1)=[O:21])([CH3:26])([CH3:25])[CH3:24]
Reactant: C=CCOC(=O)NC(Cc1cc(C2CCCN2C(=O)OC(C)(C)C)no1)(C(=O)O)C(=O)OCC
Agent: C=CCOC(=O)NC(Cc1cc(C2CCCN2C(=O)OC(C)(C)C)no1)(C(=O)OCC)C(=O)OCC
Solvent: C1COCCO1
Product: C=CCOC(=O)NC(Cc1cc(C2CCCN2C(=O)OC(C)(C)C)no1)C(=O)OCC
Temperature: 125 °C
Yield: 56 %

Procedure:
A mixture of 2-allyloxycarbonylamino-2-[3-(1-tert-butoxycarbonyl-pyrrolidin-2-yl)-isoxazol-5-ylmethyl]-malonic acid monoethyl ester and 2-allyloxycarbonylamino-2-[3-(1-tert-butoxycarbonyl-pyrrolidin-2-yl)-isoxazol-5-ylmethyl]-malonic acid diethyl ester (10.4 g, 21.5 mmol) was dissolved in dioxane (130 mL) and heated in an oil bath to 125° C. for 3 hours. The dioxane was then removed in vacuo. The residue was dissolved in ethyl acetate, washed with saturated sodium carbonate and brine, dried over magnesium sulfate and concentrated. The crude material was chromatographed on a Biotage Flash 40M column eluting with ethyl acetate/hexanes (1:4) to give the title compound as a clear oil (5.12 g, 56% 2 steps). MS (CI) m/z 338.0 (M-99). 2-Allyloxycarbonylamino-2-[3-(1-tert-butoxycarbonyl-pyrrolidin-2-yl)isoxazol-5-ylmethyl]-malonic acid diethyl ester was recovered (2.96 g, 27%). MS (CI) m/z 509.9 (M+1), 409.9 (M-99)
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[NH2:11].CN(C)[C:14]1[O:15][C:16](=[O:24])[CH:17]=[C:18]([C:20]([F:23])([F:22])[F:21])[N:19]=1>C(O)(=O)C>[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[N:11]1[C:16](=[O:24])[CH:17]=[C:18]([C:20]([F:23])([F:22])[F:21])[NH:19][C:14]1=[O:15]
Reactant: Nn1ncc2c(Cl)cccc21
Reactant: CN(C)c1nc(C(F)(F)F)cc(=O)o1
Solvent: CC(=O)O
Product: O=c1cc(C(F)(F)F)[nH]c(=O)n1-n1ncc2c(Cl)cccc21
Reaction time: 4 h
Yield: 83.5 %

Procedure:
The crude 168A (1.15 g, 6.88 mmol assumed) is dissolved in glacial acetic acid (15 mL) and 2-dimethylamino4-trifluoromethyl-[1,3]oxazin-6-one (1.43 g, 6.88 mmol) is added. The mixture was stirred for 4 h under reflux, after which the acetic acid iss removed in vacuo. The residue is dissolved in ethyl acetate, washed with saturated sodium carbonate solution and water, and is subsequently dried over sodium sulfate. The crude product (1.9 g) is obtained after removal of the drying agent by filtration and evaporation of the solvent. The product (100 mg) is purified by flash chromatography (ethyl acetate/petrol ether 3/7).
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][OH:14].[N-:15]=[N+:16]=[N-:17].[Na+].C(=O)(O)[O-].[Na+]>C(O)(C)(C)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[N:15]([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][OH:14])=[N+:16]=[N-:17]
Reactant: OCCCCCCCCCCCCBr
Reactant: [N-]=[N+]=[N-]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])O
Agent: [I-]
Solvent: CC(C)(C)O
Product: [N-]=[N+]=NCCCCCCCCCCCCO
Temperature: 25 °C
Reaction time: 96 h
Yield: 91.6 %

Procedure:
A mixture of 12-bromo-1-dodecanol (246 mg, 0.927 mmol) in t-butanol (1.8 mL, 0.5 M) was treated with sodium azide (121 mg, 1.855 mmol, 2 eq), tetrabutylammonium iodide (17 mg, 0.0464 mmol, 0.05 eq) and sat. aq. sodium bicarbonate solution (0.9 mL) in that order. The mixture was stirred at room temperature for 4 days. The mixture was filtered through a plug of celite and the cake rinsed with ethyl acetate (20 mL). The combined filtrate and washings were evaporated onto silica gel and purified by flash column (2.5×18 cm, gradient elution with hexane-ethyl acetate 6:1, 4:1 to 2:1) to give 12-Azido-1-dodecanol as a colourless oil (193 mg, 92%). 1H NMR (CDCl3, 400 MHz): 3.62 (t, 2H, J=7.0, OCH2), 3.24 (t, 2H, J=7.0, NCH2), 1.61-1.51 (m, 4H), 1.35-1.25 (m, 16H).
Reaction SMILES: N#N.C([Si](C)(C)[O:8][CH:9]([C:11]1[O:12][C:13]([CH2:16][N:17]2[N:21]=[C:20]([NH:22][C:23]([C:25]3[N:26]=[C:27]([CH3:37])[O:28][C:29]=3[C:30]3[CH:31]=[C:32]([CH3:36])[CH:33]=[CH:34][CH:35]=3)=[O:24])[CH:19]=[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[N:21]=[C:20]([NH:22][C:23]([C:25]3[N:26]=[C:27]([CH3:37])[O:28][C:29]=3[C:30]3[CH:31]=[C:32]([CH3:36])[CH:33]=[CH:34][CH:35]=3)=[O:24])[CH:19]=[N:18]2)=[CH:14][N:15]=1)[CH3:10]
Reactant: Cc1cccc(-c2oc(C)nc2C(=O)Nc2cnn(Cc3cnc(C(C)O[Si](C)(C)C(C)(C)C)o3)n2)c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: N#N
Agent: [F-]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: Cc1cccc(-c2oc(C)nc2C(=O)Nc2cnn(Cc3cnc(C(C)O)o3)n2)c1
Temperature: 0 °C
Reaction time: 0.75 h

Procedure:
In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of 2-methyl-5-m-tolyl-oxazole-4-carboxylic acid (2-{2-[1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-oxazol-5-ylmethyl}-2H-[1,2,3]triazol-4-yl)-amide (109 mg, 0.21 mmol) in dry THF (2.0 mL) was treated at 0° C. with TBAF (0.41 mL of a 1M solution in THF, 0.41 mmol). The reaction mixture was stirred at 0° C. for 45 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 (19:1 CH2Cl2-MeOH) gave the title compound as a yellow oil. TLC:rf (19:1 CH2Cl2-MeOH)=0.23. LC-MS-conditions 02: tR=0.95 min; [M+H]+=409.78.
Reaction SMILES: [CH3:1][C:2]1([CH3:14])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:10]=[N:11][NH:12][CH:13]=2)[O:3]1.[C:15]([CH:17]=[CH:18][CH2:19][CH:20]1[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]1)#[N:16].N12CCCN=C1CCCCC2>C(#N)C>[C:15]([CH2:17][CH:18]([N:12]1[CH:13]=[C:9]([B:4]2[O:5][C:6]([CH3:7])([CH3:8])[C:2]([CH3:14])([CH3:1])[O:3]2)[CH:10]=[N:11]1)[CH2:19][CH:20]1[CH2:21][CH2:22][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:24][CH2:25]1)#[N:16]
Reactant: CC1(C)OB(c2cn[nH]c2)OC1(C)C
Reactant: CC(C)(C)OC(=O)N1CCC(CC=CC#N)CC1
Solvent: C1CCC2=NCCCN2CC1
Solvent: CC#N
Product: CC(C)(C)OC(=O)N1CCC(CC(CC#N)n2cc(B3OC(C)(C)C(C)(C)O3)cn2)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 80.1 %

Procedure:
To a solution of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (1.28 g, 6.60 mmol) in acetonitrile (33.0 mL) was added tert-butyl 4-(3-cyanoprop-2-en-1-yl)piperidine-1-carboxylate (3.30 g, 13.2 mmol), followed by 1,8-diazabicyclo[5.4.0]undec-7-ene (0.987 mL, 6.60 mmol). The resulting mixture was stirred at room temperature overnight. After evaporating the reaction mixture to dryness, the residue was purified on silica gel, eluting with 0-50% EtOAc in hexanes, to give the desired product (2.35 g, 80%). LCMS (M+H) 445.2
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[CH2:13][CH2:12][CH2:11][C:10]=2[C:14]#[N:15])=[CH:4][CH:3]=1>[Ti](Cl)(Cl)(Cl)Cl.[OH-].[Na+]>[NH2:15][C:14]1[C:4]2[CH:3]=[C:2]([Br:1])[CH:7]=[CH:6][C:5]=2[N:8]=[C:9]2[CH2:13][CH2:12][CH2:11][C:10]=12
Reactant: N#CC1=C(Nc2ccc(Br)cc2)CCC1
Agent: Cl[Ti](Cl)(Cl)Cl
Agent: [Na+]
Agent: [OH-]
Product: Nc1c2c(nc3ccc(Br)cc13)CCC2
Temperature: 140 °C

Procedure:
Under nitrogen, titanium tetrachloride (1.2 ml, 11 mmol) was added to the above enamine (Example 22) (2.6 g, 20 mmol) and the stirred mixture was heated at 140° C. for 1 hour. After cooling, 10M-sodium hydroxide solution (20 ml) was added and the mixture heated under reflux for 1 hour. After being allowed to cool, this mixture was filtered and the solids washed with dichloromethane. Any organics in the filtrate were also extracted into dichloromethane. All extracts were combined, dried (Na2SO4), filtered and the solvent evaporated. Kugelrohr distillation (180° C., 0.04 mmHg) gave the product as a pale yellow powder.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][C:12]=1Cl)[C:7]([OH:9])=[O:8])([O-:3])=[O:2].[CH3:14][NH2:15]>O>[N+:1]([C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][C:12]=1[NH:15][CH3:14])[C:7]([OH:9])=[O:8])([O-:3])=[O:2]
Reactant: O=C(O)c1ccc(Cl)c([N+](=O)[O-])c1
Reactant: CN
Solvent: O
Product: CNc1ccc(C(=O)O)cc1[N+](=O)[O-]
Yield: 86 %

Procedure:
A mixture comprising 3-nitro-4-chlorobenzoic acid (1.3 g, 6.45 mmol), 10% methylamine and water (10 mL) in a sealed tube was heated at 100° C. for 11 hours, concentrated to 1 mL and then diluted with concentrated hydrochloric acid to give a yellow precipitate. The precipitate was isolated by filtration, washed with water and then diethyl ether and dried to provide 3-nitro-4-methylaminobenzoic acid (2.1 g, 86% yield); 1H-NMR (300 Mhz, CDCL3): 8.56 (d, 1H, J=2.1 Hz), 8.52 (q, 1H, J=8.6 Hz), 7.94 (dd, 1H, 9.3, 2.1 Hz), 7.00 (d, 1H, J=9.3 Hz), 2.97 (d, 3H, J=8.6 Hz).
Reaction SMILES: [NH2:1][C:2]1[N:6]=[C:5]([S:7][CH2:8][CH2:9][CH2:10][S:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[NH:4][N:3]=1.C(SCCSCCSC1N=C2N(N=1)[C:36]([OH:39])=[CH:35][C:34]([CH3:40])=N2)CCCCC>>[CH2:12]([S:11][CH2:10][CH2:9][CH2:8][S:7][C:5]1[N:6]=[C:2]2[N:3]([N:4]=1)[C:36]([OH:39])=[CH:35][C:34]([CH3:40])=[N:1]2)[CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: CCCCCSCCCSc1nc(N)n[nH]1
Reactant: CCCCCCSCCSCCSc1nc2nc(C)cc(O)n2n1
Product: CCCCCSCCCSc1nc2nc(C)cc(O)n2n1

Procedure:
Compound 18 was prepared from Compound 9, using a procedure analogous to that described previously for Compound 20. The crude product was recrystallized from ethyl acetate to give a 24% yield of white solid, m.p. 121°-123° C. Analysis: Calculated for C14H22N4OS2 : C, 51.50; H, 6.79; N, 17.16. Found: C, 61.30; H, 6.69; N, 16.97.
Reaction SMILES: N12CCCN=C1CCCCC2.[F:12][C:13]([F:27])([F:26])[C:14]1[CH:19]=[CH:18][N:17]=[C:16]([C:20]2[NH:21][O:22][C:23](=[O:25])[N:24]=2)[CH:15]=1.[CH:28]([N:31]([CH:35]([CH3:37])[CH3:36])[C:32](Cl)=[O:33])([CH3:30])[CH3:29]>N1C=CC=CC=1>[F:27][C:13]([F:12])([F:26])[C:14]1[CH:19]=[CH:18][N:17]=[C:16]([C:20]2[N:24]([C:32]([N:31]([CH:35]([CH3:37])[CH3:36])[CH:28]([CH3:30])[CH3:29])=[O:33])[C:23](=[O:25])[O:22][N:21]=2)[CH:15]=1
Reactant: O=c1nc(-c2cc(C(F)(F)F)ccn2)[nH]o1
Reactant: CC(C)N(C(=O)Cl)C(C)C
Solvent: C1CCC2=NCCCN2CC1
Solvent: c1ccncc1
Product: CC(C)N(C(=O)n1c(-c2cc(C(F)(F)F)ccn2)noc1=O)C(C)C
Reaction time: 8 h
Yield: 19.4 %

Procedure:
To 1 ml of pyridine were added 0.28 g of 1,8-diazabicyclo[5,4,0]undec-7-ene, and 0.3 g of 3-(4-trifluoromethylpyridin-2-yl)-1,2,4-oxadiazol-5-one, and 0.3 g of N,N-diisopropylcarbamoyl chloride was added at room temperature. After stirring for 8 hours, the resultant solution was concentrated, and the residue was subjected to silica gel column chromatography to obtain 0.09 g of 3-(4-trifluoromethylpyridin-2-yl)-N,N-diisopropyl-1,2,4-oxadiazol-5-one-4-carboxamide (present compound (18)).