Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]([C:11]([N+:16]([O-:18])=[O:17])=[CH:12][C:13]=1[O:14][CH3:15])[CH:9]=[O:10].[OH-:19].[Na+].OO>CO>[Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]([C:11]([N+:16]([O-:18])=[O:17])=[CH:12][C:13]=1[O:14][CH3:15])[C:9]([OH:19])=[O:10]
Reactant: [OH-]
Reactant: COc1cc([N+](=O)[O-])c(C=O)cc1OCCCCl
Agent: OO
Agent: [Na+]
Solvent: CO
Product: COc1cc([N+](=O)[O-])c(C(=O)O)cc1OCCCCl
Yield: 86 %

Procedure:
Methanol (4 lt), 3-(3-chloropropoxy)-4-methoxy-6-nitro benzaldehyde (560 gm) and 30% methanolic NaOH solution (5 ml) were heated to 45° C. To this reaction mass 35% of H2O2 solution (1200 ml) was added drop wise in 3-4 hours maintaining a pH of 10.5-11.5 with 30% methanolic NaOH solution. The reaction mass was quenched into ice water (10 kg) and the pH adjusted to 2.0-3.0 using hydrochloric acid. The solid obtained was filtered, washed with 50% aqueous methanol (500 ml) and dried at 45-50° C. to yield the title compound (510 gm, 86% yield).
Reaction SMILES: [Si:1]([O:8][CH2:9][CH2:10]/[C:11](=[CH:16]\[N:17](C)C)/[C:12]([O:14][CH3:15])=[O:13])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[NH:20]([C:22]1[CH:27]=[C:26]([C:28]#[N:29])[CH:25]=[CH:24][N:23]=1)N.C(O)(=O)C.C([O-])(O)=O.[Na+]>C(O)C>[Si:1]([O:8][CH2:9][CH2:10]/[C:11](=[CH:16]\[NH:17][NH:20][C:22]1[CH:27]=[C:26]([C:28]#[N:29])[CH:25]=[CH:24][N:23]=1)/[C:12]([O:14][CH3:15])=[O:13])([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:2])[CH3:3]
Reactant: N#Cc1ccnc(NN)c1
Reactant: COC(=O)/C(=C/N(C)C)CCO[Si](C)(C)C(C)(C)C
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Solvent: CC(=O)O
Product: COC(=O)/C(=C/NNc1cc(C#N)ccn1)CCO[Si](C)(C)C(C)(C)C
Temperature: 90 °C
Yield: 68.9 %

Procedure:
Charged methyl (2E)-4-[tert-butyl(dimethyl)silyl]oxy-2-(dimethylaminomethylidene)butanoate (7.33 g, 50%, 12.72 mmol), 2-hydrazinopyridine-4-carbonitrile (1.70 g, 12.72 mmol), acetic acid (10 mL) and ethanol (50 mL) to a flask, the mixture was heated to 90° C. for 30 min, cooled to r.t. and basified with NaHCO3 at 0° C. to pH=8. It was then extracted with ethyl acetate twice, concentrated and purified by silica gel chromatograph (PE/EA=10/1) to give the title compound (3.3 g, 34%). 1H NMR (400 MHz, CDCl3): δ 0.04 (6H, d, J=1.6 Hz), 0.89 (9H, s), 1.96-2.17 (2H, m), 3.59 (1H, q, J=6.4 Hz), 3.69 (2H, d, J=6.0 Hz), 3.74 (3H, s), 6.91-6.92 (1H, m), 7.19 (1H, d, J=6.0 Hz), 7.38 (1H, s), 8.22 (1H, d, J=5.2 Hz), 8.33 (1H, s). [M+H] Calc'd for C18H28N4O3Si, 377. Found, 377.
Reaction SMILES: CN(C=O)C.S(Cl)(Cl)=O.[NH:10]1[C:14]([C:15]([OH:17])=O)=[N:13][N:12]=[N:11]1.[CH3:18][C:19]1[S:20][CH:21]=[C:22]([NH2:24])[N:23]=1>C(#N)C.N1C=CC=CC=1.O.C1C=CC=CC=1>[CH3:18][C:19]1[S:20][CH:21]=[C:22]([NH:24][C:15]([C:14]2[NH:13][N:12]=[N:11][N:10]=2)=[O:17])[N:23]=1
Reactant: O=C(O)c1nnn[nH]1
Reactant: Cc1nc(N)cs1
Solvent: O
Solvent: O=S(Cl)Cl
Solvent: CC#N
Product: Cc1nc(NC(=O)c2nnn[nH]2)cs1
Temperature: 25 °C
Yield: 41.1 %

Procedure:
A mixture, obtained by adding dry DMF(0.43 ml, 5.55 mmol) and then thionyl chloride (0.405 ml, 5.55 mmol) to dry benzene (1 ml) under ice-cooling, was allowed to warm up to room temperature and to react for 10 minutes upon which the mixture separated into two layers. The lower layer was added dropwise to dipotassium salt of 1H-tetrazole-5-carboxylic acid (704 mg, 3.70 mmol) suspended in dry acetonitrile (9 ml) under ice-cooling, and the mixture was allowed to react for 15 minutes. After adding dropwise a mixed solution of 2-methyl-4-thiazolamine (447.8 mg, 3.92 mmol) in dry acetonitrile (5 ml) and dry pyridine (1 ml) under the same conditions, the mixture was allowed to warm up to room temperature and to react for 1 hour. To the reaction mixture was added water, and the insoluble solids was removed by filtration and the filtrate was acidified with ice-cooled 2N HCl to pH 2. The precipitates were filtered, washed with water, and recrystallized from DMF-water to give yellowish crystals (320 mg, yield 41%) of N-(2-methyl-4-thiazolyl)-1H-tetrazole-5-carboxamide (Ia-1), m.p. 295°-297° C. (decomp).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([Br:23])[N:9]([CH:20]([CH3:22])[CH3:21])[C:10]=1[CH:11]([C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=1)[OH:12])=[O:5])[CH3:2].ClC1C=CC([CH:29]=[O:30])=CC=1>>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([Br:23])[N:9]([C@H:20]([CH3:22])[CH2:21][O:30][CH3:29])[C:10]=1[CH:11]([C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=1)[OH:12])=[O:5])[CH3:2]
Reactant: CCOC(=O)c1nc(Br)n(C(C)C)c1C(O)c1ccc(Cl)cc1
Reactant: O=Cc1ccc(Cl)cc1
Product: CCOC(=O)c1nc(Br)n([C@H](C)COC)c1C(O)c1ccc(Cl)cc1

Procedure:
The title compound was obtained in analogy to the procedure described for intermediate B but using 4-chlorobenzaldehyde and the product from step 256.5. After completion, the reaction mixture was quenched with a 1M NH4Cl solution and extracted with EtOAc. The organic layer was dried (Na2SO4), filtered and concentrated. The residue was purified by flas chromatography (heptane/EtOAc, 80:20→20:80) to give the title compound. tR: 1.08 min (LC-MS 2); ESI-MS: 431.1/433.0 [M+H]+ (LC-MS 2).
Reaction SMILES: P(OCC)(OCC)OCC.[Br:11][C:12]1[C:13]([Cl:22])=[CH:14][C:15]2[C:16]([CH:21]=1)=[N+:17]([O-])[O:18][N:19]=2.[O-]Cl.[Na+]>C(O)C>[Br:11][C:12]1[C:13]([Cl:22])=[CH:14][C:15]2=[N:19][O:18][N:17]=[C:16]2[CH:21]=1
Reactant: [O-][n+]1onc2cc(Cl)c(Br)cc21
Agent: CCOP(OCC)OCC
Agent: [Na+]
Agent: [O-]Cl
Solvent: CCO
Product: Clc1cc2nonc2cc1Br
Temperature: 79 °C
Reaction time: 4 h

Procedure:
P(OEt)3 (0.9 mL, 903 mg, 5.4 mmol) was added to a solution of bromide 93 (904 mg, 3.6 mmol) in ethanol at 79° C. The resulting mixture was stirred at 79° C. for 4 h. The mixture was then cooled in an ice bath and NaOCl (19 mL of a 10-15% sol, 1.2 g, 16 mmol) was added. The solution was cooled and concentrated under reduced pressure to provided crude 94.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][CH:5]([C:10]1[C:11]([CH3:29])=[N:12][C:13]([N:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)=[N:14][C:15]=1[C:16]1[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=1)[C:6]([O:8]C)=[O:7].[OH-].[Na+]>CO>[CH3:1][O:2][CH2:3][CH2:4][CH:5]([C:10]1[C:11]([CH3:29])=[N:12][C:13]([N:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)=[N:14][C:15]=1[C:16]1[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=1)[C:6]([OH:8])=[O:7]
Reactant: COCCC(C(=O)OC)c1c(C)nc(N2CCCCC2)nc1-c1ccc(C)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: COCCC(C(=O)O)c1c(C)nc(N2CCCCC2)nc1-c1ccc(C)cc1
Yield: 40.6 %

Procedure:
This compound was prepared according to general method D from methyl 4-methoxy-2-(4-methyl-2-(piperidin-1-yl)-6-p-tolylpyrimidin-5-yl)butanoate (0.018 g; 0.045 mmol), sodium hydroxide 10N (0.045 mL; 0.45 mmol) in methanol (0.4 mL) to afford 0.007 g (38%) of the title compound as a white solid.
Reaction SMILES: [F:1][C:2]1[C:7]([F:8])=[C:6]([C:9]([F:12])([F:11])[F:10])[C:5]([F:13])=[C:4]([F:14])[C:3]=1[N:15]1[C:19]([NH:20][C:21]([CH3:23])=[O:22])=[CH:18][CH:17]=[N:16]1.S(Cl)([Cl:27])(=O)=O>C(Cl)Cl>[Cl:27][C:18]1[CH:17]=[N:16][N:15]([C:3]2[C:4]([F:14])=[C:5]([F:13])[C:6]([C:9]([F:12])([F:10])[F:11])=[C:7]([F:8])[C:2]=2[F:1])[C:19]=1[NH:20][C:21]([CH3:23])=[O:22]
Reactant: O=S(=O)(Cl)Cl
Reactant: CC(=O)Nc1ccnn1-c1c(F)c(F)c(C(F)(F)F)c(F)c1F
Solvent: ClCCl
Product: CC(=O)Nc1c(Cl)cnn1-c1c(F)c(F)c(C(F)(F)F)c(F)c1F
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 94.9 %

Procedure:
A solution of 0.80 gram (0.0023 mole) of 1-(2,3,5,6-tetrafluoro-4-trifluoromethylphenyl)-5-methylcarbonylaminopyrazole (Step C of Example 1) in 25 mL of methylene chloride was cooled to -5° C. Sulfuryl chloride (9.35 gram, 0.0026 mole) was added dropwise during a two minute period. After the addition was complete, the reaction mixture was allowed to warm to room temperature and was stirred for 1.5 hours. The reaction mixture was diluted with methylene chloride and washed in succession with an aqueous, saturated sodium bicarbonate solution and water. The organic phase was evaporated under reduced pressure to yield 0.82 gram of 4-chloro-1-(2,3,5,6-tetrafluoro-4-trifluoromethylphenyl)-5-methylcarbonylaminopyrazole as a white solid, m.p. 45°-47° C. The nmr spectrum was consistent with the proposed structure.
Reaction SMILES: [C:1]([N:8]1[CH2:11][CH:10]([C:12]([OH:14])=O)[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[NH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C1CCC(N=C=NC2CCCCC2)CC1>C(Cl)Cl>[C:16]1([NH:15][C:12]([CH:10]2[CH2:9][N:8]([C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])[CH2:11]2)=[O:14])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: Nc1ccccc1
Reactant: CC(C)(C)OC(=O)N1CC(C(=O)O)C1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CC(C(=O)Nc2ccccc2)C1
Temperature: 25 °C
Reaction time: 3 h
Yield: 96 %

Procedure:
To a solution of N-Boc-3-Azetidinecarboxylic acid 46 (0.50 g, 2.48 mmol) and aniline (274 μL, 1.1 eq.) in 5 mL of dry CH2Cl2 was added DCC (730 mg, 1.1 eq.) in one portion at 0° C. The mixture was stirred at room temperature for 3 hours. Filtration and removal of the solvent gave an oily crude product, which was purified by flash column chromatography (silica gel, hexane:ethyl acetate) to afford 1-Boc-Azetidine-3-carboxylic acid phenylamide 47 as a colorless oil (660 mg, 96%).
Reaction SMILES: C([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][C:12]=1[Cl:18])C=C.O.CN1C[CH2:24][CH2:23][C:22]1=O>>[CH2:24]([C:10]1[CH:9]=[CH:8][CH:7]=[C:6]([C:11]2[C:12]([Cl:18])=[CH:13][CH:14]=[CH:15][C:16]=2[Cl:17])[C:5]=1[OH:4])[CH:23]=[CH2:22]
Reactant: C=CCOc1ccccc1-c1c(Cl)cccc1Cl
Reactant: CN1CCCC1=O
Solvent: O
Product: C=CCc1cccc(-c2c(Cl)cccc2Cl)c1O
Reaction time: 120 h
Yield: 83 %

Procedure:
A solution of 2′-(allyloxy)-2,6-dichloro-1,1′-biphenyl (5.7 g, 0.0204 mol) in anhydrous 1-methyl-2-pyrrolidinone (50 mL) was heated to 180° C. for 42 hours then at 190° C. for 5 days. The cooled reaction mixture was poured into water (300 mL), the mixture stirred vigorously for 15 minutes then the resulting oily suspension extracted with ethyl acetate (400 mL). The organic extract was washed with water (300 mL) and saturated brine (300 mL), dried over magnesium sulfate and concentrated under reduced pressure to afford a brown oil. Purification by flash chromatography using a solvent gradient of 2 to 4% ethyl acetate in hexane gave 4.71 g (83%) of 3-allyl-2′,6′-dichloro-1,1′-biphenyl-2-ol as a colorless oil. MS (ES) m/z 278.9 ([M+H]+).
Reaction SMILES: [N+:1]([C:4]1[CH:17]=[CH:16][CH:15]=[CH:14][C:5]=1[CH2:6][N:7]1[CH2:12][CH2:11][CH:10]([OH:13])[CH2:9][CH2:8]1)([O-:3])=[O:2].C(N(CC)CC)C.[C:25](Cl)(=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>C1(C)C=CC=CC=1>[C:25]([O:13][CH:10]1[CH2:11][CH2:12][N:7]([CH2:6][C:5]2[CH:14]=[CH:15][CH:16]=[CH:17][C:4]=2[N+:1]([O-:3])=[O:2])[CH2:8][CH2:9]1)(=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: O=[N+]([O-])c1ccccc1CN1CCC(O)CC1
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: O=C(OC1CCN(Cc2ccccc2[N+](=O)[O-])CC1)c1ccccc1
Yield: 67.1 %

Procedure:
0.5 g (0.00212 mol) of 1-(2-nitro-benzyl)-piperidin-4-ol and 0.595 ml (0.00424 mol) of triethylamine were dissolved in 15 ml of toluene, treated with 0.295 ml (0.00254 mol) of benzoyl chloride and boiled at reflux for 18 hrs. The reaction mixture was concentrated and the residue was chromatographed over silica gel with ethyl acetate/hexane (1 :2). 0.484 g (75%) of 1-(2-nitro-benzyl)-piperidin-4-yl benzoate was obtained as a yellow oil. MS: me/e=341 (C19H21N2O4+).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]=[C:9]=[S:10].[Cl:11][C:12]1[CH:17]=[C:16]([C:18]([NH:20][NH2:21])=O)[CH:15]=[CH:14][N:13]=1>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:18]([C:16]2[CH:15]=[CH:14][N:13]=[C:12]([Cl:11])[CH:17]=2)=[N:20][N:21]=[C:9]1[SH:10]
Reactant: NNC(=O)c1ccnc(Cl)c1
Reactant: S=C=Nc1ccccc1Cl
Solvent: CN(C)C=O
Product: Sc1nnc(-c2ccnc(Cl)c2)n1-c1ccccc1Cl
Temperature: 25 °C
Reaction time: 18 h
Yield: 571 %

Procedure:
A mixture of 1-chloro-2-isothiocyanatobenzene 1 (0.4 g, 2.33 mmol) and 2-chloropyridine-4-carbohydrazide 11 (0.4 g, 2.33 mmol) in DMF was stirred at ambient temperature for 18 hours, concentrated to dryness, and 20 mL of 10% K2CO3 (aq.) was added. The resulting mixture was stirred under reflux for 6 hours. The clear solution was cooled to ambient temperature, washed with ether, and acidified with 1N HCl. The solid was collected, washed with H2O and ether, and dried to afford compound 13 (4.3 g). Yield: 86%.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:20]=[CH:19][C:18]=1[OH:27].O>CN(C=O)C>[CH:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:20]=[CH:19][C:18]=1[O:27][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1
Reactant: Oc1ccc2ccccc2c1
Reactant: O=[N+]([O-])c1ccc(F)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1ccc(Oc2ccc3ccccc3c2)cc1
Temperature: 80 °C

Procedure:
To a stirred solution of 1-fluoro-4-nitrobenzene (10 mmol) in DMF (20 mL) at rt, solid potassium carbonate (30 mmol) was added followed by addition of 2-naphthol (10 mmol) to the reaction mixture and heating to 80° C. until the reaction was complete as indicated by TLC or HPLC. After cooling to rt, the reaction mixture was poured into H2O (100 mL), extracted with EtOAc (2×50 mL), washed with H2O (2×50 mL) and brine (50 mL), and dried over sodium sulfate. The solvent was removed in vacuuo to afford the desired 4-(naphthalen-2-yloxy)-1-nitrobenzene. The crude product was used for further transformation.
Reaction SMILES: OCCCCCCCCN[C:11]([C:13]1[CH:14]=[C:15]([S:19]([C:22]2[CH:23]=[C:24]3[C:29](=[C:30]([CH3:32])[CH:31]=2)[N:28]=[CH:27][C:26]([C:33]([NH2:35])=[O:34])=[C:25]3[NH:36][C:37]2[CH:42]=[CH:41][CH:40]=[C:39]([O:43][CH3:44])[CH:38]=2)(=[O:21])=[O:20])[CH:16]=[CH:17][CH:18]=1)=[O:12].[NH2:45][C:46]1[CH:51]=[CH:50][C:49]([CH2:52][CH2:53][CH2:54][CH2:55][O:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][N:63]([CH2:71][C@@H:72]([C:81]2[CH:90]=[CH:89][C:88]([O:91][C:92]([O:94][C:95]([CH3:98])([CH3:97])[CH3:96])=[O:93])=[C:87]3[C:82]=2[CH:83]=[CH:84][C:85](=[O:99])[NH:86]3)[O:73][Si:74]([C:77]([CH3:80])([CH3:79])[CH3:78])([CH3:76])[CH3:75])[C:64](=[O:70])[O:65][C:66]([CH3:69])([CH3:68])[CH3:67])=[CH:48][CH:47]=1>>[C:95]([O:94][C:92]([O:91][C:88]1[CH:89]=[CH:90][C:81]([C@@H:72]([O:73][Si:74]([C:77]([CH3:80])([CH3:79])[CH3:78])([CH3:76])[CH3:75])[CH2:71][N:63]([CH2:62][CH2:61][CH2:60][CH2:59][CH2:58][CH2:57][O:56][CH2:55][CH2:54][CH2:53][CH2:52][C:49]2[CH:48]=[CH:47][C:46]([NH:45][C:11](=[O:12])[C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([S:19]([C:22]4[CH:23]=[C:24]5[C:29](=[C:30]([CH3:32])[CH:31]=4)[N:28]=[CH:27][C:26]([C:33](=[O:34])[NH2:35])=[C:25]5[NH:36][C:37]4[CH:42]=[CH:41][CH:40]=[C:39]([O:43][CH3:44])[CH:38]=4)(=[O:20])=[O:21])[CH:14]=3)=[CH:51][CH:50]=2)[C:64](=[O:70])[O:65][C:66]([CH3:69])([CH3:68])[CH3:67])=[C:82]2[C:87]=1[NH:86][C:85](=[O:99])[CH:84]=[CH:83]2)=[O:93])([CH3:98])([CH3:97])[CH3:96]
Reactant: COc1cccc(Nc2c(C(N)=O)cnc3c(C)cc(S(=O)(=O)c4cccc(C(=O)NCCCCCCCCO)c4)cc23)c1
Reactant: CC(C)(C)OC(=O)Oc1ccc([C@H](CN(CCCCCCOCCCCc2ccc(N)cc2)C(=O)OC(C)(C)C)O[Si](C)(C)C(C)(C)C)c2ccc(=O)[nH]c12
Product: COc1cccc(Nc2c(C(N)=O)cnc3c(C)cc(S(=O)(=O)c4cccc(C(=O)Nc5ccc(CCCCOCCCCCCN(C[C@H](O[Si](C)(C)C(C)(C)C)c6ccc(OC(=O)OC(C)(C)C)c7[nH]c(=O)ccc67)C(=O)OC(C)(C)C)cc5)c4)cc23)c1

Procedure:
The title compound was synthesized in a manner analogous to that described for Intermediate 70, using Intermediate 108 in place of 8-aminooctanol. ES/MS calcd. for C68H87N6O13SSi+ 1255.6. Found m/z=1256 (M+H)+.
Reaction SMILES: [Na].[CH2:2]1[O:26][C:5]2([CH2:22][CH2:21][C@@:20]3([CH3:23])[C@@H:7]([CH2:8][CH2:9][C@@H:10]4[C@@H:19]3[CH2:18][CH2:17][C@@:15]3([CH3:16])[C@H:11]4[CH2:12][C@H:13]([OH:25])[C@H:14]3[NH2:24])[CH2:6]2)[O:4][CH2:3]1.[CH:27](OCC)=[O:28]>C(O)C>[CH2:3]1[O:4][C:5]2([CH2:22][CH2:21][C@@:20]3([CH3:23])[C@@H:7]([CH2:8][CH2:9][C@@H:10]4[C@@H:19]3[CH2:18][CH2:17][C@@:15]3([CH3:16])[C@H:11]4[CH2:12][C@H:13]([OH:25])[C@H:14]3[NH:24][CH:27]=[O:28])[CH2:6]2)[O:26][CH2:2]1
Reactant: CCOC=O
Reactant: C[C@]12CCC3(C[C@@H]1CC[C@@H]1[C@@H]2CC[C@]2(C)[C@H](N)[C@@H](O)C[C@@H]12)OCCO3
Agent: [Na]
Solvent: CCO
Product: C[C@]12CCC3(C[C@@H]1CC[C@@H]1[C@@H]2CC[C@]2(C)[C@H](NC=O)[C@@H](O)C[C@@H]12)OCCO3

Procedure:
Sodium (0.37 g) was added to a stirred suspension of 17α-amino-16β-hydroxy-5α-androstan-3-one ethylene acetal (5.5 g) in ethyl formate (55 ml) and ethanol (27.5 ml) and the stirred mixture was heated under reflux for 11/2 h. After removal of the solvent, the residue was dissolved in chloroform and the solution was washed with water and dried (MgSO4). Evaporation of the solvent and crystallisation of the product from chloroform-ethyl acetate gave 17α-formamido-16β-hydroxy-5α-androstan-3-one ethylene acetal (4.5 g). A second recrystallisation furnished an analytical sample m.p. 277°-280° C., [α]DDMSO +58° (C 1.0).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].Br[CH:10]([CH3:15])[C:11]([O:13][CH3:14])=[O:12].[I-].[K+].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][CH:10]([CH3:15])[C:11]([O:13][CH3:14])=[O:12])[CH:6]=[CH:7][CH:8]=1
Reactant: COC(=O)C(C)Br
Reactant: Nc1cccc(Cl)c1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)C(C)Nc1cccc(Cl)c1
Temperature: 100 °C
Reaction time: 5 h
Yield: 24.8 %

Procedure:
To a sealed tube containing a clear, slightly yellow solution of 3-chloroaniline (2.5 g, 19.60 mmol) and methyl 2-bromopropanoate (3.93 g, 23.52 mmol) in DMF (39.2 mL) was added potassium iodide (0.325 g, 1.960 mmol) and potassium carbonate (4.06 g, 29.4 mmol). The vessel was sealed with a Teflon screw cap possessing an o-ring. The resulting suspension was warmed to 100° C. After 5 h, the resulting dark brown reaction mixture was stopped and cooled to rt. The reaction was filtered to remove the solid, rinsing with EtOAc. The filtrate was partitioned between EtOAc and water and the layers were separated. The aqueous layer was extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated to give a brown liquid weighing 6.30 g. Purification by normal phase chromatography gave the desired product (1.04 g, 25%) as a clear, yellow oil. MS (ESI) m/z: 214.0 (M+H)+.
Reaction SMILES: [CH3:1][N:2]([CH3:11])[C:3]([N:5]1[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1)=O.[O:12]1[CH2:17][CH2:16][N:15]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[N:24]2CCOCC2)[CH2:14][CH2:13]1.P(Cl)(Cl)(Cl)=O>C1C=CC=CC=1>[CH3:1][N:2]([CH3:11])[C:3]([N:5]1[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1)=[N:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[N:15]1[CH2:16][CH2:17][O:12][CH2:13][CH2:14]1
Reactant: c1ccc(N2CCOCC2)c(N2CCOCC2)c1
Reactant: CN(C)C(=O)N1CCCCC1
Solvent: O=P(Cl)(Cl)Cl
Solvent: c1ccccc1
Product: CN(C)C(=Nc1ccccc1N1CCOCC1)N1CCCCC1

Procedure:
Reaction of 1-dimethylcarbamoylpiperidine (3.7 g) in benzene (25 ml) with 4-(2-morpholinophenyl)morpholine (3.5 g) in the presence of phosphorus oxychloride for 35 hours at 80°-85° C. gave N,N-dimethyl-N'-(2-morpholinophenyl)piperidine-1-carboxamidine (m.p. 88°-90° C.) which was recrystallised from petroleum ether (b.p. 40°-60° C.)
Reaction SMILES: [CH3:1][C:2]1([CH3:16])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:10]=[C:11]([OH:15])[CH:12]=[CH:13][CH:14]=2)[O:3]1.Cl[CH2:18][C:19]([NH:21][CH3:22])=[O:20].C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[CH3:22][NH:21][C:19](=[O:20])[CH2:18][O:15][C:11]1[CH:12]=[CH:13][CH:14]=[C:9]([B:4]2[O:3][C:2]([CH3:16])([CH3:1])[C:6]([CH3:7])([CH3:8])[O:5]2)[CH:10]=1
Reactant: CC1(C)OB(c2cccc(O)c2)OC1(C)C
Reactant: CNC(=O)CCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CNC(=O)COc1cccc(B2OC(C)(C)C(C)(C)O2)c1
Temperature: 80 °C
Reaction time: 8 h
Yield: 72 %

Procedure:
A mixture of 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (220 mg, 1.0 mmol), 2-chloro-N-methylacetamide (129 mg, 1.2 mmol), and K2CO3 (207 mg, 1.5 mmol) in DMF (1.5 mL) was stirred at 80° C. overnight. The mixture was poured into water and extracted with EtOAc. The combined extracts were dried over Na2SO4, filtered, and concentrated. The residue was purified by chromatography to give the title compound in the yield of 72%. MS (m/z): 292 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[C:3]([O:18][CH3:19])=[CH:4][C:5]2[CH2:11][N:10]([CH2:12][CH3:13])[CH2:9][C:8](=[O:14])[N:7]([CH2:15][CH3:16])[C:6]=2[CH:17]=1.Cl[C:21]1[N:26]=[C:25]([NH:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[S:34]([N:37]([CH3:39])[CH3:38])(=[O:36])=[O:35])[C:24]([Cl:40])=[CH:23][N:22]=1>>[Cl:40][C:24]1[C:25]([NH:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[S:34]([N:37]([CH3:39])[CH3:38])(=[O:36])=[O:35])=[N:26][C:21]([NH:1][C:2]2[C:3]([O:18][CH3:19])=[CH:4][C:5]3[CH2:11][N:10]([CH2:12][CH3:13])[CH2:9][C:8](=[O:14])[N:7]([CH2:15][CH3:16])[C:6]=3[CH:17]=2)=[N:22][CH:23]=1
Reactant: CN(C)S(=O)(=O)c1ccccc1Nc1nc(Cl)ncc1Cl
Reactant: CCN1CC(=O)N(CC)c2cc(N)c(OC)cc2C1
Product: CCN1CC(=O)N(CC)c2cc(Nc3ncc(Cl)c(Nc4ccccc4S(=O)(=O)N(C)C)n3)c(OC)cc2C1

Procedure:
The title compound was prepared from 8-Amino-1,4-diethyl-7-methoxy-1,3,4,5-tetrahydro-benzo[e][1,4]diazepin-2-one and 2-(2,5-Dichloro-pyrimidin-4-ylamino)-N,N-dimethyl-benzenesulfonamide in an analogous manner to example 730 (0.042 g, 34%). Mp 195-197° C.; LCMS (m/e) 574 (M); 1H-NMR (DMSO, 400 MHz) δ 9.27 (s, 1H), 8.30 (s, 2H), 7.86 (s, 1H), 7.80-7.78 (d, 1H, J=7.83 Hz), 7.50-7.43 (t, 1H, J=9.18 Hz), 7.30-7.26 (t, 1H, J=7.58 Hz), 7.07 (s, 1H), 3.84 (s, 1H), 3.51 (s, 3H), 2.96 (s, 2H), 2.65 (s, 1H), 2.59-2.53 (q, 2H, J=7.08 Hz), 1.08-1.05 (t, 3H, J=7.33 Hz), 0.90-0.86 (t, 3H, J=6.83 Hz).
Reaction SMILES: [CH3:1][C:2]([CH3:10])=[CH:3][CH2:4]/[CH:5]=[C:6](/[CH:8]=[CH2:9])\[CH3:7].C([O-])(=[O:13])C.[Na+].C(OO)(=O)C>C(Cl)Cl>[CH3:1][C:2]([CH3:10])=[CH:3][CH2:4][C@@H:5]1[O:13][C@@:6]1([CH:8]=[CH2:9])[CH3:7]
Reactant: C=C/C(C)=C/CC=C(C)C
Reactant: CC(=O)[O-]
Agent: CC(=O)OO
Agent: [Na+]
Solvent: ClCCl
Product: C=C[C@@]1(C)O[C@H]1CC=C(C)C
Temperature: 0 °C
Reaction time: 1 h
Yield: 90 %

Procedure:
A solution of 204 g. of trans-ocimene and 150 g. of sodium acetate in 750 ml. of methylene chloride was stirred for one hour at room temperature, then it was cooled to 0° C. within about 15 min. Then, the addition of a solution of 3 g. of sodium acetate in 315 g. of 42% peracetic acid was started dropwise at a rate adjusted so that the temperature rose to 20°-25°. Without removing the cooling device but by maintaining a suitable rate of addition, the temperature was kept constant until the addition of the peracetic acid was completed. Under these conditions, the addition took one hour. The mixture was stirred for an additional four hours period at room temperature then the solid was removed by filtration and rinsed with methylene chloride. The combined methylene chloride solutions were poured into ice-water, the resulting mixture was shaken vigorously and the organic layer was separated and washed with 125 ml. portions of the following solvents: water (1 fold), saturated Na2CO3 (2 fold), water (1 fold). After the usual drying and concentrating procedure, distillation of the residue gave 205 g. of trans-epoxyocimene (90% yield), b.p. 45°-47°/0.1 Torr. d420 = 0.9082; nD20 = 1.4802.