Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C@@H:12]2[CH2:17][CH2:16][CH2:15][CH2:14][C@H:13]2[CH2:18][OH:19])(=[O:10])=[O:9])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]2[N:38]=[CH:37][O:36][N:35]=2)=[CH:30][C:29]=1[F:39].O1C=NC(C2C=CC(CN([C@@H]3CCCC[C@H]3CO)S(C3C=CC(Cl)=CC=3)(=O)=O)=CC=2)=N1>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH2:27][C:28]2[CH:33]=[CH:32][C:31]([C:34]3[N:38]=[CH:37][O:36][N:35]=3)=[CH:30][C:29]=2[F:39])[C@@H:12]2[CH2:17][CH2:16][CH2:15][CH2:14][C@H:13]2[CH2:18][OH:19])(=[O:9])=[O:10])=[CH:4][CH:3]=1
Reactant: O=S(=O)(N[C@@H]1CCCC[C@H]1CO)c1ccc(Cl)cc1
Reactant: Fc1cc(-c2ncon2)ccc1CBr
Agent: O=C([O-])[O-]
Agent: O=S(=O)(c1ccc(Cl)cc1)N(Cc1ccc(-c2ncon2)cc1)[C@@H]1CCCC[C@H]1CO
Agent: [Cs+]
Product: O=S(=O)(c1ccc(Cl)cc1)N(Cc1ccc(-c2ncon2)cc1F)[C@@H]1CCCC[C@H]1CO
Yield: 23.7 %

Procedure:
The title compound was synthesized from 4-chloro-N-(trans-2-(hydroxymethyl)cyclohexyl)benzenesulfonamide (200 mg, 0.66 mmol), cesium carbonate (257 mg, 0.79 mmol), and 3-(4-(bromomethyl)-3-fluorophenyl)-1,2,4-oxadiazole (204 mg, 0.79 mmol) according to the procedure described for N-(4-(1,2,4-oxadiazol-3-yl)benzyl)-4-chloro-N-(trans-2-(hydroxymethyl)cyclohexyl)benzenesulfonamide (Example 11) to give 4-chloro-N-(2-fluoro-4-(1,2,4-oxadiazol-3-yl)benzyl)-N-(trans-2-(hydroxymethyl)cyclohexyl)benzenesulfonamide (75 mg, 24%). 1H NMR (400 MHz, CDCl3) δ ppm 8.77 (s, 1H), 7.91 (dd, J=8.06, 1.51 Hz, 1H), 7.81 (t, J=7.81 Hz, 1H), 7.76 (d, J=10.20 Hz, 1H), 7.74 (d, J=8.60 Hz, 2H), 7.49 (d, J=8.60 Hz, 2H), 4.61 (d, J=15.86 Hz, 1H), 4.40 (d, J=15.61 Hz, 1H), 3.54-3.73 (m, 2H), 3.08 (dd, J=11.96, 1.64 Hz, 1H), 2.64 (br. s., 1H), 1.56-1.78 (m, 3H), 1.49 (ddd, J=12.21, 9.44, 9.32 Hz, 2H), 0.97-1.21 (m, 4H). Analytical HPLC R.T.=23.76 min. MS [M+H]+=480; [M+Na]+=502. HRMS [M+H]+ calcd 480.1160, found 480.1157.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([N+:13]([O-])=O)[C:5]([CH3:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[Cl-].[NH4+].O>CO.[Fe]>[NH2:13][C:4]1[C:5]([CH3:12])=[C:6]([CH:11]=[C:2]([Br:1])[CH:3]=1)[C:7]([O:9][CH3:10])=[O:8]
Reactant: COC(=O)c1cc(Br)cc([N+](=O)[O-])c1C
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CO
Product: COC(=O)c1cc(Br)cc(N)c1C
Temperature: 70 °C
Reaction time: 2 h
Yield: 58.5 %

Procedure:
To a solution of methyl 5-bromo-2-methyl-3-nitrobenzoate (6.3 g, 21 mmol) in methanol (150 ml) was added ammonium chloride (11.0 g, 210 mmol) followed by deionized water (75 ml). The mixture was heated to 70° C. before the addition of iron (7.0 g, 125 mmol). The reaction mixture was stirred at 70° C. for 2 hours, before being allowed to cool to room temperature and filtered through Kieselgel. The filter pad was washed with MeOH (150 ml) and the filtrate concentrated in-vacuo. The residue was dissolved in saturated NaHCO3 (aq) (50 ml) and EtOAc (150 ml). The phases were separated and the organic phase was washed with saturated NaHCO3 (aq) (3×50 ml), dried over MgSO4, filtered and concentrated in-vacuo. The residue was purified by flash column chromatography (50 g silica Isolute cartridge, 5-20% EtOAc:Heptanes) to give the title compound (3.0 g, 51%) as a thick pale yellow oil. LC-MS 87%, m/z=243.9, 244.9, 245.9, 246.9; 1H NMR (500 MHz, Chloroform-d) δ ppm 7.34 (d, J=1.89 Hz, 1H) 6.95 (d, J=1.89 Hz, 1H) 3.88 (s, 3H) 3.80 (br. s., 2H) 2.29 (s, 3H).
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4]1[C:9](=[O:10])[N:8]2[CH2:11][CH2:12][CH2:13][CH2:14][C:7]2=[N:6][C:5]1=[O:15].C(N(CC)CC)C.[CH3:23][S:24](Cl)(=[O:26])=[O:25]>C(#N)C>[CH3:23][S:24]([O:1][CH2:2][CH2:3][N:4]1[C:9](=[O:10])[N:8]2[CH2:11][CH2:12][CH2:13][CH2:14][C:7]2=[N:6][C:5]1=[O:15])(=[O:26])=[O:25]
Reactant: CS(=O)(=O)Cl
Reactant: O=c1nc2n(c(=O)n1CCO)CCCC2
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CS(=O)(=O)OCCn1c(=O)nc2n(c1=O)CCCC2
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 94.9 %

Procedure:
To an ice-cooled solution of 1.80 g of 3-(2-hydroxyethyl)-6,7,8,9-tetrahydro-2H-pyrido[1,2-a]-1,3,5-triazine-2,4(3H)-dione prepared in Reference Example 27 and 1.20 g of triethylamine in 25 ml of acetonitrile, 1.17 g of methanesufonyl chloride was added dropwise. After stirring for 30 minutes, the mixture was concentrated to dryness, and the residue was extracted with chloroform. Concentration of the chloroform solution gave 2.34 g of the entitled compound as an yellow oil.
Reaction SMILES: [CH2:1](Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[NH:15]1[C:23]2[C:18](=[CH:19][C:20]([OH:24])=[CH:21][CH:22]=2)[CH:17]=[N:16]1.O>CN(C)C=O>[CH2:1]([O:24][C:20]1[CH:19]=[C:18]2[C:23](=[CH:22][CH:21]=1)[NH:15][N:16]=[CH:17]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: BrCc1ccccc1
Reactant: Oc1ccc2[nH]ncc2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: c1ccc(COc2ccc3[nH]ncc3c2)cc1
Temperature: 40 °C
Reaction time: 2 h
Yield: 37.7 %

Procedure:
Benzyl bromide (0.089 ml, 0.745 mmol) and potassium carbonate (103 mg, 0.745 mmol) were added to a solution of the 1H-indazol-5-ol (100 mg, 0.745 mmol) obtained in Reference Example 4 in N,N-dimethylformamide (2 ml), and the resulting mixture was heated to 40° C. After 2 hours, the mixture was poured into water (20 ml) and extracted with ethyl acetate (20 ml×2). The organic layer was dried over anhydrous magnesium sulfate. The organic layer dried was concentrated under reduced pressure and the resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate) to obtain 5-(benzyloxy)-1H-indazole (63 mg, 38%).
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH2:10][O:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[NH:19][C:20](=O)[C:21]3[C:26]([CH:27]=2)=[CH:25][CH:24]=[CH:23][CH:22]=3)=[CH:14][C:13]=1[O:29][CH3:30])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:33])=O>>[CH2:1]([O:8][CH2:9][CH2:10][O:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[N:19]([Cl:33])[CH2:20][C:21]3[C:26]([CH:27]=2)=[CH:25][CH:24]=[CH:23][CH:22]=3)=[CH:14][C:13]=1[O:29][CH3:30])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: COc1cc(-c2cc3ccccc3c(=O)[nH]2)ccc1OCCOCc1ccccc1
Product: COc1cc(C2=Cc3ccccc3CN2Cl)ccc1OCCOCc1ccccc1

Procedure:
The resulting 3-[4-(2-benzyloxyethoxy)-3-methoxyphenyl]isoquinolin-1-one (3.15 g) was reacted with phosphorus oxychloride (20 ml) according to the method of Example 10-2, to give 3-[4-(2-benzyloxyethoxy)-3-methoxyphenyl)-2-chloroisoquinoline. Then, N-ethylpiperazine (30 ml) and potassium carbonate (1.83 g) were added to the resulting compound as it was. The resulting mixture was reacted at 90° C. overnight. The reaction solution was evaporated, and to the resulting residue were added ethyl acetate and purified water. The ethyl acetate layer was washed with water and brine, and dried over magnesium sulfate. The solvent was evaporated, to give 3-[4-(2-benzyloxyethoxy)-3-methoxyphenyl]-1-(4-ethylpiperazin-1-yl)isoquinoline.
Reaction SMILES: C(N(CC)CC)C.[C:8](Cl)(=[O:12])[CH2:9][CH2:10][CH3:11].[NH2:14][C:15]1[S:16][C:17]([CH:20]([CH3:22])[CH3:21])=[CH:18][N:19]=1>ClCCl>[CH:20]([C:17]1[S:16][C:15]([NH:14][C:8](=[O:12])[CH2:9][CH2:10][CH3:11])=[N:19][CH:18]=1)([CH3:22])[CH3:21]
Reactant: CC(C)c1cnc(N)s1
Reactant: CCCC(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCC(=O)Nc1ncc(C(C)C)s1
Temperature: -5 °C
Reaction time: 2 h
Yield: 50.1 %

Procedure:
Triethylamine (0.97 ml; 6.34 mmol) and butanoyl chloride (0.52 ml; 5.07 mmol) were added in this order to a solution of 2-amino-5-isopropyl-1,3-thiazole (0.6 g; 4.23 mmol) in dichloromethane (8 ml), cooled to −5° C. The reaction mixture was stirred at −5° C. for 2 hours and then warmed to room temperature. After additional 4 hours, the organic layer was washed with water, saturated sodium bicarbonate, 1N hydrochloric acid, brine, dried over sodium sulfate and evaporated. The residue was recrystallized from cyclohexane to yield 0.45 g (50%) of the title compound as a colourless solid (m.p. 95–97° C.)
Reaction SMILES: C1C=CC2N(O)N=NC=2C=1.[Cl:11][C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[NH:17][C:16]([C:21]([OH:23])=O)=[CH:15]2.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.[NH2:44][CH:45]1[CH2:54][C:53]2[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=2)[N:47]([CH2:55][CH2:56][CH2:57][O:58][Si:59]([C:62]([CH3:65])([CH3:64])[CH3:63])([CH3:61])[CH3:60])[C:46]1=[O:66]>C(Cl)Cl>[Si:59]([O:58][CH2:57][CH2:56][CH2:55][N:47]1[C:48]2[C:53](=[CH:52][CH:51]=[CH:50][CH:49]=2)[CH2:54][CH:45]([NH:44][C:21]([C:16]2[NH:17][C:18]3[C:14]([CH:15]=2)=[CH:13][C:12]([Cl:11])=[CH:20][CH:19]=3)=[O:23])[C:46]1=[O:66])([C:62]([CH3:64])([CH3:65])[CH3:63])([CH3:61])[CH3:60]
Reactant: CC(C)(C)[Si](C)(C)OCCCN1C(=O)C(N)Cc2ccccc21
Reactant: O=C(O)c1cc2cc(Cl)ccc2[nH]1
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC(C)(C)[Si](C)(C)OCCCN1C(=O)C(NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
Yield: 82.3 %

Procedure:
Prepared exactly as in Method 7 using HOBT (174 mg, 1.3 mmol), 5-chloroindole-2-carboxylic acid (250 mg, 1.3 mmol), DIPEA (0.22 mL, 1.3 mmol), EDCI (308 mg, 1.6 mmol) and 3-amino-1-(3-{[tert-butyl(dimethyl)silyl]oxy}propyl)-3,4-dihydroquinolin-2(1H)-one (Method 14, 432 mg, 1.3 mmol) in DCM (10 mL). This gave the title compound (548 mg, 82%) as a pale yellow solid.
Reaction SMILES: Cl.C(OC([N:9]1[CH2:14][CH2:13][CH2:12][C@H:11]([O:15][C:16]2[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=2[NH:23][C:24]2[C:25]3[C:32]([CH3:33])=[C:31]([C:34]([OH:36])=[O:35])[S:30][C:26]=3[N:27]=[CH:28][N:29]=2)[CH2:10]1)=O)(C)(C)C>CO.O1CCOCC1>[F:22][C:20]1[CH:19]=[CH:18][C:17]([NH:23][C:24]2[C:25]3[C:32]([CH3:33])=[C:31]([C:34]([OH:36])=[O:35])[S:30][C:26]=3[N:27]=[CH:28][N:29]=2)=[C:16]([O:15][C@H:11]2[CH2:12][CH2:13][CH2:14][NH:9][CH2:10]2)[CH:21]=1
Reactant: Cc1c(C(=O)O)sc2ncnc(Nc3ccc(F)cc3O[C@H]3CCCN(C(=O)OC(C)(C)C)C3)c12
Agent: Cl
Solvent: C1COCCO1
Solvent: CO
Product: Cc1c(C(=O)O)sc2ncnc(Nc3ccc(F)cc3O[C@H]3CCCNC3)c12

Procedure:
HCl in Methanol (4M; 0.250 ml) was added into a solution of 4-[2-((S)-1-tert-butoxycarbonyl-piperidin-3-yloxy)-4-fluoro-phenylamino]-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylic acid (50 mg) in dioxane (2.5 ml) at room temperature. The reaction was stirred over the weekend. The reaction mixture was purified by chromatography. The product was triturated from hot MeOH to give the intended product.
Reaction SMILES: [Si](OCCN(C)C(C1C(OCC2C=CC=CC=2)=C(O)N=C(CC2(C3C4C(=CC=CC=4)C=CC=3)CCCC2)N=1)=O)(C(C)(C)C)(C)C.[CH2:46]([O:53][C:54]1[C:55]([C:77]([OH:79])=O)=[N:56][C:57]([CH2:61][C:62]2([C:67]3[C:76]4[C:71](=[CH:72][CH:73]=[CH:74][CH:75]=4)[CH:70]=[CH:69][CH:68]=3)[CH2:66][CH2:65][CH2:64][CH2:63]2)=[N:58][C:59]=1[OH:60])[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1.[Si:80]([O:87][CH2:88][CH2:89][NH:90][CH:91]([CH3:93])[CH3:92])([C:83]([CH3:86])([CH3:85])[CH3:84])([CH3:82])[CH3:81]>>[CH2:46]([O:53][C:54]1[C:55]([C:77]([N:90]([CH2:89][CH2:88][O:87][Si:80]([C:83]([CH3:85])([CH3:84])[CH3:86])([CH3:81])[CH3:82])[CH:91]([CH3:92])[CH3:93])=[O:79])=[N:56][C:57]([CH2:61][C:62]2([C:67]3[C:76]4[C:71](=[CH:72][CH:73]=[CH:74][CH:75]=4)[CH:70]=[CH:69][CH:68]=3)[CH2:66][CH2:65][CH2:64][CH2:63]2)=[N:58][C:59]=1[OH:60])[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1
Reactant: CC(C)NCCO[Si](C)(C)C(C)(C)C
Reactant: O=C(O)c1nc(CC2(c3cccc4ccccc34)CCCC2)nc(O)c1OCc1ccccc1
Agent: CN(CCO[Si](C)(C)C(C)(C)C)C(=O)c1nc(CC2(c3cccc4ccccc34)CCCC2)nc(O)c1OCc1ccccc1
Product: CC(C)N(CCO[Si](C)(C)C(C)(C)C)C(=O)c1nc(CC2(c3cccc4ccccc34)CCCC2)nc(O)c1OCc1ccccc1

Procedure:
This compound was prepared by following the same method as described for 5-benzyloxy-6-hydroxy-2-(1-naphthalen-1-yl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-methyl-amide (350) from 5-benzyloxy-6-hydroxy-2-(1-naphthalen-1-yl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid (345) and [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-isopropyl-amine (8b).
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][CH2:3][CH:2]1[C:6]([O:8][CH2:9][CH2:10][CH2:11][C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1)=[O:7].[C:18]1([CH2:24][S:25](Cl)(=[O:27])=[O:26])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(N(CC)CC)C>C(Cl)Cl>[C:18]1([CH2:24][S:25]([N:1]2[CH2:5][CH2:4][CH2:3][C@H:2]2[C:6]([O:8][CH2:9][CH2:10][CH2:11][C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)=[O:7])(=[O:27])=[O:26])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: O=C(OCCCc1cccnc1)C1CCCN1
Reactant: O=S(=O)(Cl)Cc1ccccc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(OCCCc1cccnc1)[C@@H]1CCCN1S(=O)(=O)Cc1ccccc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 42.9 %

Procedure:
A solution of 3-(3-Pyridyl)-1-propyl pyrrolidine-2-carboxylate (200 mg; 0.9 mmol) and α-toluenesulfonyl chloride (160 mg; 0.9 mmol) in methylene chloride (20 mL) was treated with triethylamine (90 mg; 0.9 mmol) and stirred for 2 hours at room temperature. The reaction mixture was filtered to remove solids and applied directly to a silica gel column, eluting with 50% ethyl acetate in hexane, to obtain 150 mg (43%) of Compound 4 (Table I) as a clear oil. 1H NMR (300 MHz, CDCl3): δ1.81-1.85 (m, 2H); 1.95-2.02 (m, 3H); 2.10-2.25 (m, 1H); 2.69-2.74 (t, 2H); 2.85-2.97 (m, 1H); 3.24-3.27 (m, 1H); 4.16-4.20 (m, 2H); 4.29 (d, 1H); 4.34 (m, 1H); 4.45 (d, 1H); 7.20-7.25 (m, 1H); 7.35 (m, 3H); 7.49-7.52 (m, 3H); 8.46 (s, 2H). Analysis calculated for C20H24N2O3S: C, 61.83; H, 6.23; N, 7.21. Found: C, 61.59; H, 6.24; N, 7.17.
Reaction SMILES: CCN(CC)CC.[N:8]1([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1.[Cl:21][C:22]1[S:26][C:25]([NH:27][C:28]([CH:30]([C:38]2[CH:43]=[CH:42][C:41]([S:44](Cl)(=[O:46])=[O:45])=[CH:40][CH:39]=2)[CH2:31][CH:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)=[O:29])=[N:24][CH:23]=1>CC(N(C)C)=O>[Cl:21][C:22]1[S:26][C:25]([NH:27][C:28]([CH:30]([C:38]2[CH:39]=[CH:40][C:41]([S:44]([N:11]3[CH2:12][CH2:13][N:8]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9][CH2:10]3)(=[O:46])=[O:45])=[CH:42][CH:43]=2)[CH2:31][CH:32]2[CH2:33][CH2:34][O:35][CH2:36][CH2:37]2)=[O:29])=[N:24][CH:23]=1
Reactant: O=C(Nc1ncc(Cl)s1)C(CC1CCOCC1)c1ccc(S(=O)(=O)Cl)cc1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Solvent: CC(=O)N(C)C
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1CCN(S(=O)(=O)c2ccc(C(CC3CCOCC3)C(=O)Nc3ncc(Cl)s3)cc2)CC1
Reaction time: 16 h

Procedure:
NEt3 (278 μL, 2.0 mmol) and tert-butyl piperazine-1-carboxylate (373 mg, 2.0 mmol) were added to a stirred solution of 4-[1-(5-chlorothiazol-2-ylcarbamoyl)-2-(tetrahydropyran-4-yl)ethyl]benzenesulfonyl chloride (Preparation 60, 449 mg, 1.0 mmol) in anhydrous DMAc (4 mL). The mixture was stirred for 16 h, then the solvents were removed in vacuo. The residue was dissolved in EtOAc (50 mL) to give a solution that was washed with H2O (15 mL), saturated aqueous Na2CO3 (15 mL), and brine (15 mL), before being dried (MgSO4). Filtration, solvent evaporation, and column chromatography (IH-EtOAc, 7:3 to 1:1) gave tert-butyl 4-{4-[1-(5-chlorothiazol-2-ylcarbamoyl)-2-(tetrahydropyran-4-yl)ethyl]benzenesulfonyl}piperazine-1-carboxylate: m/z (ES+)=599.5 [M+H]+. A solution of this compound (189 mg, 316 μmol) in CH2Cl2-TFA (1:1, 7 mL) was stirred for 1 h. The solvents were evaporated off under reduced pressure, then the residue was triturated with Et2O. The product was collected, washed with Et2O, and air-dried to furnish the trifluoroacetate salt of the title compound: RTA=2.64 min; m/z (ES+)=499.3 [M+H]+.
Reaction SMILES: [CH3:1][C:2]1([CH3:19])[CH:7]=[C:6]([C:8]2[C:13]([CH3:14])=[CH:12][CH:11]=[CH:10][N:9]=2)[C:5]2[CH:15]=[CH:16][CH:17]=[CH:18][C:4]=2[O:3]1.C(O)(=O)C>C(O)C.[Pd]>[CH3:1][C:2]1([CH3:19])[CH2:7][CH:6]([C:8]2[C:13]([CH3:14])=[CH:12][CH:11]=[CH:10][N:9]=2)[C:5]2[CH:15]=[CH:16][CH:17]=[CH:18][C:4]=2[O:3]1
Reactant: Cc1cccnc1C1=CC(C)(C)Oc2ccccc21
Agent: [Pd]
Solvent: CC(=O)O
Solvent: CCO
Product: Cc1cccnc1C1CC(C)(C)Oc2ccccc21
Yield: 46.8 %

Procedure:
2.97 g of 2,2-dimethyl-4-(3-methyl-2-pyridyl)-2H-1-benzopyran were dissolved in 50 ml of ethanol and shaken at room temperature under a hydrogen atmosphere with 10% palladium-on-charcoal in the presence of 0.5 ml of acetic acid. After 24 hours the catalyst was filtered off and the filtrate was evaporated. The residue was chromatographed on silica gel using ethyl acetate/petroleum ether (1:4) for the elution. There were obtained 1.4 g of 3,4-dihydro-2,2-dimethyl-4-(3-methyl-2-pyridyl)-2H-1-benzopyran together with mixed fractions containing this compound and starting material. The procedure described above was carried out on the mixed fractions to give 675 mg of 3,4-dihydro-2,2-dimethyl-4-(3-methyl-2-pyridyl)-2H-1-benzopyran which was recrystallized from t-butyl methyl ether and then melted at 100°-102° C.
Reaction SMILES: C(Cl)Cl.[CH2:4]([OH:12])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][C:10]#[CH:11].Br[C:14]1[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=1>C(N(CC)CC)C>[N:16]1[CH:17]=[CH:18][CH:19]=[C:14]([C:11]#[C:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][OH:12])[CH:15]=1
Reactant: Brc1cccnc1
Reactant: C#CCCCCCCO
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: OCCCCCCC#Cc1cccnc1
Yield: 91.1 %

Procedure:
A flame-dried, 22-L flask equipped with a mechanical stirrer, condenser, and a gas inlet tube dipping below the surface of the solvent was charged with 4.0 L of methylene chloride, 1.25 L of triethylamine, 385 g of 7-octyn-1-ol, and 285 mL (456 g) of 3-bromopyridine. The reagents were rinsed into the flask with an additional 100 mL of methylene chloride. Argon was bubbled through the reaction mixture for 30 minutes. The flask was evacuated for 3 minutes at 70 mm. The vacuum was released by bubbling in argon. This process was repeated six times and then 42 g of dichlorobis(triphenyl phosphine)palladium (II) and 4 g of cuprous iodide were added. The mixture was heated at a gentle reflux for 18 hours and cooled to 20°. To the mixture was added, with vigorous stirring, 8.0 L of ether. A small amount of yellowish-white solid was removed by filtration and washed with 2×1.5 L=3.0 L of ether. The combined filtrate was washed with 3.0 L of deionized water and 2×3.0 L=6.0 L of 1N hydrochloric acid. The combined aqueous solutions were washed with 2×2.5 L=5.0 L of ether. The organic solutions were discarded and the aqueous solution was made strongly basic by the addition of 2.50 L of 20% sodium hydroxide solution. The resulting mixture was extracted with 3×4.0 L=12.0 L of methylene chloride. The extracts were dried over sodium sulfate and filtered through Celite. Solvent removal on a rotary evaporator at 45° gave 534.2 g (91% yield) of a pale brown 8-(3-pyridinyl)-7-octyn-1-ol having a strong odor of 3-bromopyridine. No further purification of this material was undertaken.
Reaction SMILES: [CH:1](=[N:8]O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:17]1([P:23](Cl)([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[O:24])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C(Cl)Cl>[C:17]1([P:23]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)(=[O:24])[N:8]=[CH:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: ON=Cc1ccccc1
Reactant: O=P(Cl)(c1ccccc1)c1ccccc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=P(N=Cc1ccccc1)(c1ccccc1)c1ccccc1
Temperature: -50 °C
Reaction time: 2 h

Procedure:
A dry 250 mL 3-necked round bottom flask, fitted with a magnetic stir bar, addition funnel and thermometer, was charged with benzaldehyde oxime (38 mmol) dissolved in petroleum ether (40 mL) and methylene chloride (40 mL) along with triethylamine (38 mmol). The flask was cooled, under an atmosphere of nitrogen, to -50° C. with a Dry Ice-chloroform bath. The addition funnel was charged with diphenylphosphinyl chloride (37 mmol) dissolved in methylene chloride (10 mL) and this solution was slowly dropped into the flask ensuring that the reaction temperature did not rise above -25° C. White precipitate formation was observed. Once the addition was complete the reaction temperature was naturally allowed to rise to room temperature over a period of 2 hours. The reaction mixture was filtered to remove the precipitate and the filtrate was concentrated by rotary evaporation which yielded a yellow oil which solidified upon standing. The structure of the product is detailed below. ##STR8##
Reaction SMILES: [F:1][C:2]1[C:10]2[N:9]([CH2:11][CH2:12][CH2:13][C:14]([CH3:19])([N+:16]([O-])=O)[CH3:15])[C:8](=[O:20])[N:7]([CH3:21])[C:6]=2[CH:5]=[CH:4][CH:3]=1.[H][H]>CO.[Ni]>[NH2:16][C:14]([CH3:19])([CH3:15])[CH2:13][CH2:12][CH2:11][N:9]1[C:10]2[C:2]([F:1])=[CH:3][CH:4]=[CH:5][C:6]=2[N:7]([CH3:21])[C:8]1=[O:20]
Reactant: Cn1c(=O)n(CCCC(C)(C)[N+](=O)[O-])c2c(F)cccc21
Reactant: [H][H]
Agent: [Ni]
Solvent: CO
Product: Cn1c(=O)n(CCCC(C)(C)N)c2c(F)cccc21

Procedure:
A solution of 2 g (6.7 mmol) 4-fluoro-1-methyl-3-(4-methyl-4-nitro-pentyl)-1,3-dihydro-benzimidazol-2-one in methanol is hydrogenated at 3 bar hydrogen pressure in the presence of Raney nickel. After separation of the catalyst hydrochloric acid in diethyl ether is added. The hydrochloride precipitated is filtered off and dried. Yield: 1.5 g (83%, hydrochloride); melting range=230-232° C.; mass spectroscopy: [M+H]+=303.
Reaction SMILES: [CH3:1][C:2]1[CH2:6][CH2:5][CH:4]([CH3:7])[CH:3]=1.[Cl:8][SiH:9]([Cl:11])[Cl:10].N(C1(C#N)CCCCC1)=NC1(C#N)CCCCC1>>[CH3:1][CH:2]1[CH2:6][CH2:5][CH:4]([CH3:7])[CH:3]1[Si:9]([Cl:11])([Cl:10])[Cl:8]
Reactant: Cl[SiH](Cl)Cl
Reactant: CC1=CC(C)CC1
Agent: N#CC1(N=NC2(C#N)CCCCC2)CCCCC1
Product: CC1CCC(C)C1[Si](Cl)(Cl)Cl
Yield: 72.5 %

Procedure:
A one-liter autoclave equipped with a stirrer was charged in a nitrogen atmosphere with 49 grams (0.51 mol) of 1,3-dimethylcyclopentene, 138 grams (1.0 mol) of trichlorosilane and 24 grams (0.1 mol) of 1,1'-azobis(cyclohexane-1-carbonitrile) and the mixture was reacted at a temperature of 130° C. for 3 days. The resulting reaction mixture was purified by distillation thereby obtaining 85 grams (0.37 mol) of 2,5-dimethylcyclopentyltrichlorosilane. The structure of the resulting product was identified by 1H-NMR analysis.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:23]=[C:22]([O:24][CH3:25])[CH:21]=[CH:20][C:4]=1[CH2:5][N:6]1[C:12](=[O:13])[C:11]2[CH:14]=[C:15]([CH3:18])[CH:16]=[CH:17][C:10]=2[NH:9][C:8](=O)[CH2:7]1.CN(C)C1C=CC(C)=CC=1.P(Cl)(Cl)([Cl:38])=O>C1(C)C=CC=CC=1>[Cl:38][C:8]1[CH2:7][N:6]([CH2:5][C:4]2[CH:20]=[CH:21][C:22]([O:24][CH3:25])=[CH:23][C:3]=2[O:2][CH3:1])[C:12](=[O:13])[C:11]2[CH:14]=[C:15]([CH3:18])[CH:16]=[CH:17][C:10]=2[N:9]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: COc1ccc(CN2CC(=O)Nc3ccc(C)cc3C2=O)c(OC)c1
Solvent: Cc1ccccc1
Solvent: Cc1ccc(N(C)C)cc1
Product: COc1ccc(CN2CC(Cl)=Nc3ccc(C)cc3C2=O)c(OC)c1
Temperature: 100 °C
Reaction time: 2.5 h

Procedure:
4-(2,4-Dimethoxy-benzyl)-7-methyl-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione (34.0 g, 100 mmol) and N,N-dimethyl-p-toluidine (28.9 mL, 200 mmol) were mixed in toluene (100 mL) and heated to 100° C. Then phosphorus oxychloride (10.1 mL, 110 mmol) was added dropwise and heating at 100° C. was continued for 2.5 h. The resulting dark red solution was used directly in the subsequent step.