Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1/[CH:8]=[C:9](/[P:14]([O:19][CH2:20][CH3:21])([O:16][CH2:17][CH3:18])=[O:15])\[C:10]([O:12][CH3:13])=[O:11].[CH:22]#[C:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C>[C:22]([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1/[CH:8]=[C:9](/[P:14]([O:19][CH2:20][CH3:21])([O:16][CH2:17][CH3:18])=[O:15])\[C:10]([O:12][CH3:13])=[O:11])#[C:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]
Reactant: C#CCCCCCCCCCCC
Reactant: CCOP(=O)(OCC)/C(=C/c1ccccc1Br)C(=O)OC
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Product: CCCCCCCCCCCC#Cc1ccccc1/C=C(\C(=O)OC)P(=O)(OCC)OCC
Temperature: 25 °C
Yield: 29.2 %

Procedure:
Methyl 3-(2-bromophenyl)-2-E-(diethoxyphosphinyl)-2-propenoate (11.31 g, 29.99 mmol) prepared according to Example 16 was mixed with 1-tridecyne (9.50 g, 52.68 mmol) and triphenylphosphine (0.214 g, 0.82 mmol) in a 500 ml four-neck round bottom flask equipped with a magnetic stir bar, condenser topped with an argon inlet, and an internal thermometer. Dry triethylamine (156 ml) was added, and the flask was closed. The system was inerted and a bubbler was connected to the argon line. Palladium acetate (0.0733 g, 0.33 mmol) was added, and the reaction mixture was heated in an oil bath (T=100° to 105° C.). The reaction was refluxed for 50 hours. At the end of this time, the reaction mixture was cooled to room temperature and was filtered. The white precipitate was washed with triethyl amine (100 ml). The filtrates were stripped down to a dark oil. This oil was extracted three times with acetonitrile (50 ml). The combined acetonitrile extracts were stripped down to an orange oil which was chromatographed on silica eluting with petroleum ether-dichloromethane (68:32) increasing to pure dichloromethane, then with hexanesethyl acetate (1:1) increasing to pure ethyl acetate. Fractions containing a spot with Rf =0.20 on silica developed with hexane-dichloromethane (68:32) were combined and stripped. Reverse phase chromatography on C18 silica, eluting with 10% water in methanol, was done. Fractions were combined which showed the above Rf. These fractions were rechromatographed on silica eluting with hexanes-ethyl acetate (66:34) and progressing to hexanes-ethyl acetate (60:40). Additional rechromatography of impure fractions gave 4.18 g (8.77 mmol, 29% yield) of pure product as a pale yellow oil. 1H NMR (CDCl3) ∂ 0.88 (t, J=6.7 Hz, 3H), 1.17 to 1.50 (several m, 22H), 1.63 quintet, J=7.6 Hz, 2H), 2.43 (t, J=7.2 Hz, 2H), 3.72 (s, 3H), 4.21 (m, 4H), 7.19 to 7.36 (several m, 3H), 7.44 (dm, J=7.6 Hz, 1H), 8.05 (d, J=23.8 Hz); EI mass spectrum m/z 476 (M+).
Reaction SMILES: [NH2:1][C:2]1[N:7]([CH2:8][CH2:9][CH3:10])[C:6](=[O:11])[NH:5][C:4](=[O:12])[C:3]=1[NH:13][C:14]([C:16]12[CH2:23][CH:22]3[CH2:24][CH:18]([CH2:19][CH:20]1[CH2:21]3)[CH2:17]2)=O.[CH2:25](Br)[CH:26]=[CH2:27]>>[CH2:27]([N:5]1[C:4](=[O:12])[C:3]2[NH:13][C:14]([C:16]34[CH2:17][CH:18]5[CH2:24][CH:22]([CH2:21][CH:20]3[CH2:19]5)[CH2:23]4)=[N:1][C:2]=2[N:7]([CH2:8][CH2:9][CH3:10])[C:6]1=[O:11])[CH:26]=[CH2:25]
Reactant: C=CCBr
Reactant: CCCn1c(N)c(NC(=O)C23CC4CC(CC2C4)C3)c(=O)[nH]c1=O
Product: C=CCn1c(=O)c2[nH]c(C34CC5CC(CC3C5)C4)nc2n(CCC)c1=O
Yield: 34.5 %

Procedure:
Substantially the same procedure as in Reference Example 3 was repeated using 300 mg (0.90 mmol) of 6-amino-5-(3-tricyclo[3.3.1.03,7 ]nonylcarbonylamino)-1-propyluracil (Japanese Published Unexamined Patent Application No. 173889/91) and 0.16 ml (1.81 mmol) of allyl bromide. The obtained crude product was subjected to the same cyclization reaction that was used in Example 1, without purification, to give 110 mg (yield 35%) of Compound J as a white powder.
Reaction SMILES: Cl[C:2]1[C:7]2[CH:8]=[CH:9][O:10][C:6]=2[C:5]([CH2:11][C:12]([NH2:14])=[O:13])=[CH:4][N:3]=1.C(CN)O.[CH3:19][N:20](C)[CH:21]=O>>[CH3:19][N:20]([CH3:21])[C:2]1[C:7]2[CH:8]=[CH:9][O:10][C:6]=2[C:5]([CH2:11][C:12]([NH2:14])=[O:13])=[CH:4][N:3]=1
Reactant: NC(=O)Cc1cnc(Cl)c2ccoc12
Reactant: CN(C)C=O
Solvent: NCCO
Product: CN(C)c1ncc(CC(N)=O)c2occc12
Temperature: 130 °C
Yield: 43 %

Procedure:
Combine 2-(4-chlorofuro[3,2-c]pyridin-7-yl)acetamide (850 mg, 4.21 mmol), dimethylformamide (5 mL) and ethanolamine (0.76 mL, 12.63 mmol). Heat the reaction at 130° C. overnight Add additional ethanolamine (0.25 ml) and heat at 130° C. overnight. Cool to room temperature, concentrate, and dilute with ethyl acetate. Wash with saturated aqueous sodium bicarbonate and concentrate. Subject to flash chromatography, eluting with ethylacetate:methanol to provide the title compound as a white solid (400 mg, 43%).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]2[CH2:24][CH2:23][CH2:22][N:12]2[C:13]=1[C:14]1[N:15]=[N:16][C:17]([NH:20][NH2:21])=[CH:18][CH:19]=1.[Si:25]([O:32][CH2:33][C:34]([CH3:38])([CH3:37])[CH:35]=O)([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26].C(O)(=O)C.C(O)(=O)C.IC1C=CC=CC=1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[Si:25]([O:32][CH2:33][C:34]([C:38]1[N:16]2[N:15]=[C:14]([C:13]3[N:12]4[CH2:22][CH2:23][CH2:24][C:11]4=[N:10][C:9]=3[C:3]3[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=3[F:1])[CH:19]=[CH:18][C:17]2=[N:20][N:21]=1)([CH3:37])[CH3:35])([C:28]([CH3:29])([CH3:30])[CH3:31])([CH3:26])[CH3:27]
Reactant: NNc1ccc(-c2c(-c3ccc(F)cc3F)nc3n2CCC3)nn1
Reactant: CC(C)(C=O)CO[Si](C)(C)C(C)(C)C
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CC(=O)O
Solvent: Ic1ccccc1
Product: CC(C)(CO[Si](C)(C)C(C)(C)C)c1nnc2ccc(-c3c(-c4ccc(F)cc4F)nc4n3CCC4)nn12
Temperature: 25 °C
Reaction time: 2 h
Yield: 90.3 %

Procedure:
2-(2,4-Difluorophenyl)-3-(6-hydrazinylpyridazin-3-yl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole (6.00 g, 18.3 mmol, Example #35, Step E) was suspended in DCM (125 μL) then 3-(tert-butyldimethylsilyloxy)-2,2-dimethylpropanal (4.15 g, 19.2 mmol, J. Org. Chem., 2002, 67, 2474-2480) was added. The mixture was stirred at ambient temperature for about 2 h. Iodobenzene diacetate (6.00 g, 18.6 mmol) was added then the mixture was stirred for about 30 min. Saturated aqueous NaHCO3 (150 mL) was added then the layers were separated. The organic layer was dried over MgSO4, filtered and concentrated in vacuo. The material was purified by flash chromatography on silica gel with EtOAc as an eluent to give the title compound (8.67 g, 90%): LC/MS (Table 1, Method g) Rt=2.77 min; MS m/z: 525.3.2 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:47]=[CH:48][C:49]=1[O:50][CH3:51])[CH2:6][NH:7][C:8](=[O:46])[C:9]1[CH:14]=[CH:13][C:12]([CH2:15][NH:16][C:17](=[O:45])[CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([CH2:25][CH:26]([NH:28][CH2:29][C@@H:30]([C:32]3[CH:33]=[N:34][C:35]([N:38]4C(C)=CC=C4C)=[CH:36][CH:37]=3)[OH:31])[CH3:27])[CH:20]=2)=[CH:11][CH:10]=1.Cl.NO>C(O)C>[NH3:7].[NH2:38][C:35]1[N:34]=[CH:33][C:32]([C@@H:30]([OH:31])[CH2:29][NH:28][CH:26]([CH3:27])[CH2:25][C:21]2[CH:20]=[C:19]([CH2:18][C:17]([NH:16][CH2:15][C:12]3[CH:13]=[CH:14][C:9]([C:8]([NH:7][CH2:6][C:5]4[CH:47]=[CH:48][C:49]([O:50][CH3:51])=[C:3]([O:2][CH3:1])[CH:4]=4)=[O:46])=[CH:10][CH:11]=3)=[O:45])[CH:24]=[CH:23][CH:22]=2)=[CH:37][CH:36]=1
Reactant: COc1ccc(CNC(=O)c2ccc(CNC(=O)Cc3cccc(CC(C)NC[C@H](O)c4ccc(-n5c(C)ccc5C)nc4)c3)cc2)cc1OC
Agent: Cl
Agent: NO
Solvent: CCO
Product: COc1ccc(CNC(=O)c2ccc(CNC(=O)Cc3cccc(CC(C)NC[C@H](O)c4ccc(N)nc4)c3)cc2)cc1OC
Product: N
Temperature: 80 °C
Yield: 130.8 %

Procedure:
A solution of N-(3,4-dimethoxy-benzyl)-4-({2-[3-(2-{(2R)-2-[6-(2,5-dimethyl-pyrrol-1-yl)-pyridin-3-yl]-2-hydroxy-ethylamino}-propyl)-phenyl]-acetylamino}-methyl)-benzamide (48 mg, 0.07 mmol) in ethanol (1 ml) was treated with hydroxylamine hydrochloride (24 mg, 0.35 mmol) and the resulting mixture heated in a Reactivial™ at 80° C. for 16 hours. The reaction mixture was cooled, passed through a Strong Cation Exchange column eluting with methanol and then 2N ammonia in methanol to elute the product. Further purification by flash column chromatography eluting with dichloromethane:methanol:880 ammonia (97:3:0.5 changing to 90:10:1 by volume) gave the title compound (28 mg) as a pale yellow foam.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:30]=[CH:29][C:11]3[N:12]([C:25]([CH3:28])([CH3:27])[CH3:26])[C:13]([C:15]4[CH:24]=[CH:23][CH:22]=[CH:21][C:16]=4[C:17]([NH:19][NH2:20])=[O:18])=[N:14][C:10]=3[CH:9]=2)=[CH:4][N:3]=1.C([O-])(O)=O.[Na+].[N:36]#[C:37]Br>O1CCOCC1.O>[NH2:36][C:37]1[O:18][C:17]([C:16]2[CH:21]=[CH:22][CH:23]=[CH:24][C:15]=2[C:13]2[N:12]([C:25]([CH3:26])([CH3:27])[CH3:28])[C:11]3[CH:29]=[CH:30][C:8]([C:5]4[CH:4]=[N:3][C:2]([NH2:1])=[N:7][CH:6]=4)=[CH:9][C:10]=3[N:14]=2)=[N:19][N:20]=1
Reactant: CC(C)(C)n1c(-c2ccccc2C(=O)NN)nc2cc(-c3cnc(N)nc3)ccc21
Reactant: N#CBr
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: CC(C)(C)n1c(-c2ccccc2-c2nnc(N)o2)nc2cc(-c3cnc(N)nc3)ccc21
Temperature: 25 °C
Reaction time: 18 h
Yield: 65.7 %

Procedure:
To a vial is added 2-[5-(2-amino-pyrimidin-5-yl)-1-tert-butyl-1H-benzimidazol-2-yl]-benzoic acid hydrazide (43 mg, 0.107 mmol) in 1,4-dioxane (2 mL), followed by the addition of NaHCO3 (13 mg, 0.155 mmol) in water (0.5 mL), then cyanogen bromide (13 mg, 0.123 mmol). The reaction mixture is stirred at room temperature for 18 hours. The reaction mixture is concentrated in vacuo. The residue is loaded to a silica gel column. The column is eluted with 0-8% 2M NH3 in MeOH/CH2Cl2. The product fractions are collected and concentrated to afford the title compound (30 mg, 66%) as an off-white solid. LCMS (ESMS): m/z 427.76 (M++1)
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([O:14][C:15](=[O:23])[C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=2)[C:9]=1[O:24][C:25](=[O:33])[C:26]1[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][CH:27]=1.[C:34]1([CH2:40][O:41][C:42](=[O:54])[C:43]2[CH:48]=[CH:47][C:46]([OH:49])=[C:45]([CH2:50][CH2:51][CH3:52])[C:44]=2[OH:53])[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.[I-].[K+].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[C:34]1([CH2:40][O:41][C:42](=[O:54])[C:43]2[CH:48]=[CH:47][C:46]([O:49][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][C:8]3[CH:13]=[CH:12][CH:11]=[C:10]([O:14][C:15](=[O:23])[C:16]4[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=4)[C:9]=3[O:24][C:25](=[O:33])[C:26]3[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][CH:27]=3)=[C:45]([CH2:50][CH2:51][CH3:52])[C:44]=2[OH:53])[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1
Reactant: CCCc1c(O)ccc(C(=O)OCc2ccccc2)c1O
Reactant: Cc1ccc(C(=O)Oc2cccc(CCCCCCBr)c2OC(=O)c2ccc(C)cc2)cc1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCCc1c(OCCCCCCc2cccc(OC(=O)c3ccc(C)cc3)c2OC(=O)c2ccc(C)cc2)ccc(C(=O)OCc2ccccc2)c1O
Yield: 31.7 %

Procedure:
A mixture of 1.91 g (3.75 mmol) of 1-(6-bromohexyl)-2,3-bis[(4-methylbenzoyl)oxy]benzene, 1.07 g (3.75 mmol) 2,4-dihydroxy-3-propylbenzoic acid phenylmethyl ester, 0.94 g (5.63 mmol) of potassium iodide and 0.75 g (5.63 mol) of potassium carbonate in 40 mL of acetone was stirred at reflux for 26 hours. The reaction mixture was filtered and the filtrate was concentrated under reduced pressue. The crude product was purified by HPLC using 5% ethyl acetate-hexane to give 0.85 g (32% yield) of 2-hydroxy-4-[6-[2,3-bis[(4-methylbenzoyl)oxy]phenyl]hexyloxy]-3-propylbenzoic acid phenylmethyl ester as an oil.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C@H:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C:13]2[CH:18]=[CH:17][N:16]3[N:19]=[CH:20][C:21]([C:22]([OH:24])=O)=[C:15]3[N:14]=2)[CH:5]=[CH:6][CH:7]=1.[NH2:25][C@H:26]1[CH2:31][CH2:30][C@H:29]([OH:32])[CH2:28][CH2:27]1>>[F:1][C:2]1[CH:3]=[C:4]([C@H:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C:13]2[CH:18]=[CH:17][N:16]3[N:19]=[CH:20][C:21]([C:22]([NH:25][C@H:26]4[CH2:31][CH2:30][C@H:29]([OH:32])[CH2:28][CH2:27]4)=[O:24])=[C:15]3[N:14]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)c1cnn2ccc(N3CCC[C@@H]3c3cccc(F)c3)nc12
Reactant: N[C@H]1CC[C@H](O)CC1
Product: O=C(N[C@H]1CC[C@H](O)CC1)c1cnn2ccc(N3CCC[C@@H]3c3cccc(F)c3)nc12

Procedure:
Prepared by the method as described in Example 1 using (R)-5-(2-(3-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (Preparation E) and (trans)-4-aminocyclohexanol to yield the title compound as a white solid (31 mg, 62% yield). MS (apci) m/z=424.1 (M+H).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:20])[NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[CH:11]=2)=[CH:4][C:3]=1[NH:21][C:22]([C:24]1[C:28]2[N:29]=[CH:30][N:31]=[C:32](S(C)=O)[C:27]=2[S:26][CH:25]=1)=[O:23].[O:36]1[CH2:41][CH2:40][N:39]([CH2:42][CH2:43][NH2:44])[CH2:38][CH2:37]1>>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:20])[NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[CH:11]=2)=[CH:4][C:3]=1[NH:21][C:22]([C:24]1[C:28]2[N:29]=[CH:30][N:31]=[C:32]([NH:44][CH2:43][CH2:42][N:39]3[CH2:40][CH2:41][O:36][CH2:37][CH2:38]3)[C:27]=2[S:26][CH:25]=1)=[O:23]
Reactant: Cc1ccc(C(=O)Nc2cccc(C(F)(F)F)c2)cc1NC(=O)c1csc2c(S(C)=O)ncnc12
Reactant: NCCN1CCOCC1
Product: Cc1ccc(C(=O)Nc2cccc(C(F)(F)F)c2)cc1NC(=O)c1csc2c(NCCN3CCOCC3)ncnc12

Procedure:
The procedure of Step 3 of Example 13 was repeated except for using the compound obtained in Step 2 of Example 13 and 2-morpholino ethaneamine to obtain the title compound (see Table 1).
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[CH:5][N:6]=1.[CH3:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([CH3:14])[C:9]=1[N+:15]#[C-:16].[N:17]1[CH:22]=[CH:21][C:20]([CH:23]=O)=[CH:19][CH:18]=1>Cl(O)(=O)(=O)=O>[CH3:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([CH3:14])[C:9]=1[NH:15][C:16]1[N:6]2[C:2]([S:3][CH:4]=[CH:5]2)=[N:1][C:23]=1[C:20]1[CH:21]=[CH:22][N:17]=[CH:18][CH:19]=1
Reactant: [C-]#[N+]c1c(C)cccc1C
Reactant: Nc1nccs1
Reactant: O=Cc1ccncc1
Agent: [O-][Cl+3]([O-])([O-])O
Product: Cc1cccc(C)c1Nc1c(-c2ccncc2)nc2sccn12

Procedure:
Compound 21 was prepared in accordance with the general synthesis instructions from 1.0 ml (0.1 mmol) 2-aminothiazole solution (0.1 M, MC), 0.575 ml (0.115 mmol) 2,6-dimethylphenylisonitrile solution (0.2 M, MC), 0.500 ml (0.15 mmol) 4-pyridinecarbaldehyde solution (0.3 M, MC) and 10 μl perchloric acid (w=20%) in a substance library.
Reaction SMILES: [CH2:1]([NH2:7])[CH:2]1[O:6][CH2:5][CH2:4][CH2:3]1.C(N(CC)CC)C.[CH3:15][C:16]1[CH:17]=[C:18]([CH:22]=[C:23]([CH3:25])[CH:24]=1)[C:19](Cl)=[O:20]>C1C=CC=CC=1>[CH2:1]([NH:7][C:19](=[O:20])[C:18]1[CH:22]=[C:23]([CH3:25])[CH:24]=[C:16]([CH3:15])[CH:17]=1)[CH:2]1[O:6][CH2:5][CH2:4][CH2:3]1
Reactant: NCC1CCCO1
Reactant: Cc1cc(C)cc(C(=O)Cl)c1
Solvent: c1ccccc1
Solvent: CCN(CC)CC
Product: Cc1cc(C)cc(C(=O)NCC2CCCO2)c1
Reaction time: 0.5 h
Yield: 62.9 %

Procedure:
A mixture was formed containing 3.0 grams (0.03 moles) of tetrahydrofurfurylamine, 4.5 ml. triethylamine in 100 ml. benzene. Then, 3.7 ml. (0.25 moles) of 3,5-dimethylbenzoylchloride was added. After standing for 1/2 hour, the mixture was washed with 100 ml. of water, 1 normal HCl (50 ml.), 50 ml. of saturated sodium bicarbonate dried over magnesium sulfate and evaporated in vacuo to yield 4.4 grams of product ND30 1.5366.
Reaction SMILES: [OH:1][CH:2]([CH2:6][CH2:7][CH2:8][CH3:9])[CH2:3][C:4]#[CH:5].[C:10]1([C:16](Br)([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.N1C=CC=CC=1>O>[C:10]1([C:16]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[O:1][CH:2]([CH2:6][CH2:7][CH2:8][CH3:9])[CH2:3][C:4]#[CH:5])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: C#CCC(O)CCCC
Reactant: BrC(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: c1ccncc1
Solvent: O
Product: C#CCC(CCCC)OC(c1ccccc1)(c1ccccc1)c1ccccc1

Procedure:
A mixture of 10 g. (0.08 moles) of 4-hydroxy-1-octyne [L. Crombie and A. G. Jacklin, J. Chem. Soc., 1632 (1957)] and 30.75 g. (0.09 moles) of triphenylmethyl bromide in 85 ml. of dry pyridine is heated on the steam bath for 2 hours. The cooled mixture is treated with water and extracted with ether. The extract is washed successively with ice cold 2% hydrochloric acid, saturated sodium chloride solution, dried with magnesium sulfate, and taken to dryness. Column chromatography of the residue on Florisil affords an oil; λ max 3.01, 4.72 (acetylenic hydrogen), 6.28, 9.65 and 14.25 mμ (triphenylmethoxy group).
Reaction SMILES: [OH:1][C@H:2]1[CH2:19][C@@:17]2([CH3:18])[C@@H:13]([CH2:14][CH2:15][C:16]2=[O:20])[C@H:12]2[C@H:3]1[C@:4]1([CH3:22])[C:9]([CH2:10][CH2:11]2)=[CH:8][C:7](=[O:21])[CH2:6][CH2:5]1.[CH:23](O)=[O:24]>Cl(O)(=O)(=O)=O>[CH:23]([O:1][C@H:2]1[CH2:19][C@@:17]2([CH3:18])[C@@H:13]([CH2:14][CH2:15][C:16]2=[O:20])[C@H:12]2[C@H:3]1[C@:4]1([CH3:22])[C:9]([CH2:10][CH2:11]2)=[CH:8][C:7](=[O:21])[CH2:6][CH2:5]1)=[O:24]
Reactant: C[C@]12CCC(=O)C=C1CC[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)C(=O)CC[C@@H]12
Reactant: O=CO
Agent: [O-][Cl+3]([O-])([O-])O
Product: C[C@]12CCC(=O)C=C1CC[C@@H]1[C@@H]2[C@@H](OC=O)C[C@]2(C)C(=O)CC[C@@H]12
Reaction time: 20 h

Procedure:
The starting 11β-formyloxy-androst-4-ene-3,17-dione was prepared from 11β-hydroxy-androst-4-ene-3,17-dione by dissolving the latter in excess formic acid in the presence of a catalytic amount of perchloric acid and, after 20 hours at room temperature, pouring the reaction mixture on ice, extracting with methylene chloride and evaporating. There was obtained a product melting at 139°-139.5° (crystallized from ethyl acetate), [α]D25 = 188° (dioxane).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([N:9]2[CH2:15][CH2:14][CH2:13][N:12]([C:16]3[CH:21]=[CH:20][C:19]([N+:22]([O-])=O)=[CH:18][CH:17]=3)[CH2:11][CH2:10]2)[CH:3]=1.C(O)C.C(N(CC)CC)C>C(OCC)(=O)C>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([N:9]2[CH2:15][CH2:14][CH2:13][N:12]([C:16]3[CH:17]=[CH:18][C:19]([NH2:22])=[CH:20][CH:21]=3)[CH2:11][CH2:10]2)[CH:3]=1
Reactant: Cc1cc(C)nc(N2CCCN(c3ccc([N+](=O)[O-])cc3)CC2)c1
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Solvent: CCO
Product: Cc1cc(C)nc(N2CCCN(c3ccc(N)cc3)CC2)c1
Temperature: 25 °C
Yield: 99.6 %

Procedure:
To a solution of 1-(4,6-dimethyl-pyridin-2-yl)-4-(4-nitro-phenyl)-[1,4]diazepane (940 mg, 2.88 mmol) in ethyl acetate (25 mL) was added stannous chloride (3.90 g, 17.3 mmol) and ethanol (5 mL). The reaction mixture was heated to reflux for 15 hours then cooled to room temperature, basified with triethylamine and filtered. The filtrate was concentrated under reduced pressure to afford 4-[4-(4,6-dimethyl-pyridin-2-yl)-[1,4]diazepan-1-yl]-phenylamine (850 mg, 99%) as a brown solid.
Reaction SMILES: BrC[C:3]1[CH:4]=[N:5][C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:7][CH:8]=1.[NH:15]1[CH:19]=[CH:18][N:17]=[CH:16]1.[C:20]([O-])([O-])=O.[K+].[K+]>C(#N)C>[N:15]1([CH2:20][C:8]2[CH:3]=[CH:4][N:5]=[C:6]([C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:7]=2)[CH:19]=[CH:18][N:17]=[CH:16]1
Reactant: c1c[nH]cn1
Reactant: O=C([O-])[O-]
Reactant: BrCc1cnc(-c2ccccc2)nc1
Agent: [K+]
Solvent: CC#N
Product: c1ccc(-c2nccc(Cn3ccnc3)n2)cc1

Procedure:
Synthesized using compound 64a (70 mg, 0.28 mmol), imidazole (76 mg, 1.12 mmol) and K2CO3 (195 mg, 1.41 mmol) in acetonitrile according to Method B. Crude product was purified by flash chromatography on silica-gel using ethyl acetate as eluent. After flash chromatography the product was recrystallized in ethyl acetate. Light yellow solid. Yield: 62 mg, 94%. 1H NMR (CDCl3, 500 MHz): δH (ppm)=5.17 (s, 2H), 6.94 (t, J=1.3 Hz, 1H), 7.15 (t, J=1.1 Hz, 1H), 7.47-7.54 (m, 3H), 7.61 (s, 1H), 8.41-8.46 (m, 2H), 8.63 (s, 2H); 13C NMR (CDCl3, 125 MHz): δC (ppm)=46.0, 118.8, 127.0, 128.2, 128.7, 130.7, 131.1, 136.8, 137.2, 156.2, 164.8; (ESI): m/z=236.92 [M+H]+.
Reaction SMILES: [C:1](Cl)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:21]([O:28][C:29]1[C:30](=[O:37])[CH2:31][C:32]([CH2:35][OH:36])=[N:33][CH:34]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.O>CN(C)C1C=CN=CC=1.CN(C)C=O>[CH2:21]([O:28][C:29]1[C:30](=[O:37])[CH2:31][C:32]([CH2:35][O:36][C:1]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[N:33][CH:34]=1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: O=C1CC(CO)=NC=C1OCc1ccccc1
Agent: CN(C)c1ccncc1
Solvent: O
Solvent: CN(C)C=O
Product: O=C1CC(COC(c2ccccc2)(c2ccccc2)c2ccccc2)=NC=C1OCc1ccccc1
Temperature: 95 °C
Yield: 42.8 %

Procedure:
4-Dimethylaminopyridine (17.55 g) and trityl chloride (40.5 g) are added to a solution of 5-benzyloxy-2-hydroxymethyl-4-pyridone (30.2 g) in dry dimethylformamide and the mixture stirred and heated at 95° C. for 2 hours. After cooling the mixture is poured into iced-water (800 mL) and the precipitate collected, washed with water (2×500 mL) and sucked dry. The solid is boiled with methanol (500 mL) and after cooling the solid is collected, washed with methanol (200 mL) and diethyl ether (2×100 mL) and dried at 80° C. to give 5-benzyloxy-2-trityloxymethyl-4-pyridone (26.5 g) as a white solid, m.p. 233-5° C.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:8][C:7]=2[CH:16]=1.[C-:17]#[N:18].[Na+].O>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.ClCCl>[C:17]([CH2:2][C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:8][C:7]=2[CH:16]=1)#[N:18]
Reactant: CCOC(=O)c1cc2cc(CCl)ccc2o1
Reactant: [C-]#N
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Product: CCOC(=O)c1cc2cc(CC#N)ccc2o1
Reaction time: 18 h
Yield: 66.7 %

Procedure:
A mixture of ethyl 5-chloromethylbenzofuran-2-carboxylate (3.0 g, 0.0126 mol), sodium cyanide (1.23 g, 0.025 mol), tetrabutylammonium bromide (0.50 g, 0.0013 mol), water (10 cm3) and dichloromethane (10 cm3) was vigorously stirred for 18 hr. at room temperature. The mixture was separated and the organic layer was washed with water, dried (Na2SO4), filtered and the solvent was removed. The residue was recrystallised from petroleum ether (b.p. 60°-80° C.) to give ethyl 5-cyanomethylbenzofuran-2-carboxylate (1.92 g, 0.0084 mol, 66.6%) m.p. 76°-77° C.-t.l.c./silica/toluene, RF 0.11.
Reaction SMILES: [OH:1][N:2]=[C:3]([CH3:12])[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=O.[C:13]([NH:16][NH2:17])([NH2:15])=[S:14].O>C(O)(=O)C>[OH:1][N:2]=[C:3]([CH3:12])[C:4](=[N:17][NH:16][C:13]([NH2:15])=[S:14])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: CC(=NO)C(=O)c1ccccc1
Reactant: NNC(N)=S
Solvent: O
Solvent: CC(=O)O
Product: CC(=NO)C(=NNC(N)=S)c1ccccc1
Temperature: 60 °C
Yield: 86.6 %

Procedure:
A mixture of 2-hydroxyiminopropiophenone (150 g) and thiosemicarbazine (90 g) in acetic acid (500 ml) was heated at 60° C. for 60 hours with stirring. After cooling, water was added to the reaction mixture. The resultant precipitates were collected by filtration, washed successively with water, methanol and diisopropyl ether, and dried to give 2-hydroxyiminopropiophenone thiosemicarbazone (188.2 g).