Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([NH:13][C:14]([C:16]2[S:17][C:18]([Cl:21])=[CH:19][CH:20]=2)=[O:15])[CH2:10][C@H:9]1[CH2:22]OS(C)(=O)=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F-:28].C([N+](CCCC)(CCCC)CCCC)CCC>CN(C=O)C.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([NH:13][C:14]([C:16]2[S:17][C:18]([Cl:21])=[CH:19][CH:20]=2)=[O:15])[CH2:10][C@H:9]1[CH2:22][F:28])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N1C[C@H](NC(=O)c2ccc(Cl)s2)C[C@H]1COS(C)(=O)=O
Reactant: [F-]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N1C[C@H](NC(=O)c2ccc(Cl)s2)C[C@H]1CF
Temperature: 80 °C
Reaction time: 19 h

Procedure:
91.1 To a stirred solution of 150 mg (2S,4R)-4-[(5-chloro-thiophene-2-carbonyl)-amino]-2-methanesulfonyloxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (example 17.2) at r.t. in 3.3 ml DMF under an argon atmosphere was added 1.71 ml tetrabutylammonium fluoride solution (1 M in THF). The mixture was heated to 80° C. and stirring at that temperature was continued for 19 h. The mixture was cooled to r.t., diluted with EtOAc and washed with H2O. The aqueous phase was back extracted with EtOAc. The combined organics were washed with H2O and brine, dried over MgSO4, filtered and concentrated. The crude product was purified by column chromatography (silica gel; cyclohexane->cyclohexane/EtOAc 1:1) to give 44 mg (2S,4R)-4-[(5-chloro-thiophene-2-carbonyl)-amino]-2-fluoromethyl-pyrrolidine-1-carboxylic acid tert-butyl ester as off-white amorphous solid. MS 361.0 ([M−H]−)
Reaction SMILES: Cl.[CH2:2]([O:9][C:10]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:11]=1[CH2:12][CH2:13][CH2:14][CH:15]2[C:20]([N:22]([C:29]1[CH:30]=[N:31][C:32]([CH:35]([CH3:37])[CH3:36])=[CH:33][CH:34]=1)[CH2:23][C:24]1[CH:25]=[N:26][NH:27][CH:28]=1)=[O:21])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl[CH2:39][C:40]1[CH:41]=[N:42][C:43]([CH:46]([CH3:48])[CH3:47])=[CH:44][CH:45]=1>>[CH2:2]([O:9][C:10]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:11]=1[CH2:12][CH2:13][CH2:14][CH:15]2[C:20]([N:22]([C:29]1[CH:30]=[N:31][C:32]([CH:35]([CH3:37])[CH3:36])=[CH:33][CH:34]=1)[CH2:23][C:24]1[CH:25]=[N:26][N:27]([CH2:39][C:40]2[CH:41]=[N:42][C:43]([CH:46]([CH3:48])[CH3:47])=[CH:44][CH:45]=2)[CH:28]=1)=[O:21])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: CC(C)c1ccc(CCl)cn1
Reactant: CC(C)c1ccc(N(Cc2cn[nH]c2)C(=O)C2CCCc3c(OCc4ccccc4)cccc32)cn1
Agent: Cl
Product: CC(C)c1ccc(Cn2cc(CN(C(=O)C3CCCc4c(OCc5ccccc5)cccc43)c3ccc(C(C)C)nc3)cn2)cn1
Yield: 83.2 %

Procedure:
By the reaction and treatment in the same manner as in Example 271 using 5-benzyloxy-N-(6-isopropylpyridin-3-yl)-N-[(pyrazol-4-yl)methyl]-1,2,3,4-tetrahydronaphthalene-1-carboxamide hydrochloride (0.78 g) and 3-chloromethyl-6-isopropylpyridine (0.51 g) as starting materials, 5-benzyloxy-N-(6-isopropylpyridin-3-yl)-N-({1-[(6-isopropylpyridin-3-yl)methyl]pyrazol-4-yl}methyl)-1,2,3,4-tetrahydronaphthalene-1-carboxamide (0.77 g) was obtained.
Reaction SMILES: [H-].[Na+].[CH3:3][N:4]([CH2:6][CH2:7][OH:8])[CH3:5].Cl[C:10]1[CH:15]=[C:14]([N:16]2[C:20]3[N:21]=[C:22]([N:50]4[CH2:55][CH2:54][O:53][CH2:52][CH2:51]4)[N:23]=[C:24]([C:25]4[CH:26]=[N:27][C:28]([N:31]([CH2:41][C:42]5[CH:47]=[CH:46][C:45]([O:48][CH3:49])=[CH:44][CH:43]=5)[CH2:32][C:33]5[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=5)=[N:29][CH:30]=4)[C:19]=3[CH2:18][CH2:17]2)[CH:13]=[CH:12][N:11]=1>C1(C)C=CC=CC=1>[CH3:3][N:4]([CH3:5])[CH2:6][CH2:7][O:8][C:12]1[CH:13]=[C:14]([N:16]2[C:20]3[N:21]=[C:22]([N:50]4[CH2:51][CH2:52][O:53][CH2:54][CH2:55]4)[N:23]=[C:24]([C:25]4[CH:30]=[N:29][C:28]([N:31]([CH2:32][C:33]5[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=5)[CH2:41][C:42]5[CH:43]=[CH:44][C:45]([O:48][CH3:49])=[CH:46][CH:47]=5)=[N:27][CH:26]=4)[C:19]=3[CH2:18][CH2:17]2)[CH:15]=[CH:10][N:11]=1
Reactant: CN(C)CCO
Reactant: COc1ccc(CN(Cc2ccc(OC)cc2)c2ncc(-c3nc(N4CCOCC4)nc4c3CCN4c3ccnc(Cl)c3)cn2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: COc1ccc(CN(Cc2ccc(OC)cc2)c2ncc(-c3nc(N4CCOCC4)nc4c3CCN4c3ccnc(OCCN(C)C)c3)cn2)cc1
Reaction time: 0.25 h
Yield: 100 %

Procedure:
Sodium hydride (15 mg, 60% mineral oil dispersion, 5 equivalents) and N,N-dimethylaminoethanol (39 μl, 5 equivalents) were added to toluene (1.3 ml). After refluxing for 5 minutes, stirring was carried out at 50° C. for 15 minutes. {5-[7-(2-Chloro-pyridin-4-yl)-2-morpholin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl]-pyrimidin-2-yl}-bis-(4-methoxy-benzyl)-amine (50 mg) obtained in Step A in Example 1-H-31 was added, followed by refluxing overnight, and the reaction mixture was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (dichloromethane/methanol=30/1 to 10/1), to obtain a colorless solid (54 mg, 100%).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4](=[O:24])[C:5]2[C:6]([C:20]([O:22][CH3:23])=[O:21])=[C:7]([CH:14]=[CH:15][C:16]([O:18][CH3:19])=[O:17])[N:8]([CH3:13])[C:9]=2[C:10](=[O:12])[CH:11]=1.[O-]S(S([O-])=O)=O.[Na+].[Na+]>C(Cl)(Cl)Cl.C(O)C>[OH:24][C:4]1[C:3]([O:2][CH3:1])=[CH:11][C:10]([OH:12])=[C:9]2[C:5]=1[C:6]([C:20]([O:22][CH3:23])=[O:21])=[C:7]([CH:14]=[CH:15][C:16]([O:18][CH3:19])=[O:17])[N:8]2[CH3:13]
Reactant: COC(=O)C=Cc1c(C(=O)OC)c2c(n1C)C(=O)C=C(OC)C2=O
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: CCO
Product: COC(=O)C=Cc1c(C(=O)OC)c2c(O)c(OC)cc(O)c2n1C

Procedure:
Methyl 5-methoxy-3-methoxycarbonyl-N-methyl-4,7-dioxo-2-indoleacrylate (18) (6.64 g, 20 mmol) was dissolved in a mixture of chloroform (600 ml) and ethanol (215 ml). The reduction was carried out on stirring with an aqueous solution (260 ml) of Na2S2O4 (42 g) at room temperature for 30 minutes.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]=[CH:7][N:8]=[C:9](OC3CCOCC3)[C:10]=2[N:11]=1.[CH3:19][O:20][C:21]1[N:26]=[CH:25][C:24]([NH2:27])=[CH:23][CH:22]=1.C([O-])(=O)C.[Na+]>CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]=[CH:7][N:8]=[C:9]([NH:27][C:24]3[CH:25]=[N:26][C:21]([O:20][CH3:19])=[CH:22][CH:23]=3)[C:10]=2[N:11]=1
Reactant: Clc1ccc2ncnc(OC3CCOCC3)c2n1
Reactant: COc1ccc(N)cn1
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Product: COc1ccc(Nc2ncnc3ccc(Cl)nc23)cn1
Yield: 59.1 %

Procedure:
A mixture of 4,6-dichloropyrido[3,2-d]pyrimidine (Intermediate 1, step D) (0.100 g, 0.500 mmol), 6-methoxypyridin-3-amine (0.155 g, 1.250 mmol) and sodium acetate (0.123 g, 1.50 mmol) in 5 ml of solvent (THF:H2O=1:1) was refluxed for 1 hour. The reaction mixture was diluted with EtOAc. The organics were washed with brine, dried over Na2SO4, filtered and concentrated. The crued was purified by column chromatography on SiO2 (Hex:EtOAc=1:1) to get 6-chloro-N-(6-methoxypyridin-3-yl)pyrido[3,2-d]pyrimidin-4-amine (0.085 g, 59%) as a yellow solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 3.97 (3H, s), 6.85 (1H, d, J=8.8 Hz), 7.71 (1H, d, J=8.8 Hz), 8.14 (1H, d, J=8.8 Hz), 8.20 (1H, dd, J=2.8, 8.8 Hz), 8.55 (1H, d, J=2.8 Hz), 8.67 (1H, br s), 8.73 (1H, s).
Reaction SMILES: Cl.[NH2:2][CH:3]1[C:15]2[N:14]3[CH:16]=[CH:17][N:18]=[C:13]3[C:12](=[O:19])[NH:11][C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]1=2.[C:20](Cl)(=[O:24])[CH:21]([CH3:23])[CH3:22].C(N(CC)CC)C.C>CN(C)C=O.CO>[C:20]([NH:2][CH:3]1[C:15]2[N:14]3[CH:16]=[CH:17][N:18]=[C:13]3[C:12](=[O:19])[NH:11][C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]1=2)(=[O:24])[CH:21]([CH3:23])[CH3:22]
Reactant: NC1c2ccccc2-c2[nH]c(=O)c3nccn3c21
Reactant: CC(C)C(=O)Cl
Agent: Cl
Solvent: CO
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CC(C)C(=O)NC1c2ccccc2-c2[nH]c(=O)c3nccn3c21
Temperature: -10 °C
Reaction time: 1 h
Yield: 33.9 %

Procedure:
To a suspension of 1 g of 10-amino-5H,10H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one hydrochloride in 50 ml of anhydrous dimethylformamide, maintained under an argon atmosphere at a temperature in the region of -10° C., are successively added 0.9 g of isobutyryl chloride and a solution of 0.4 g of triethylamine in 5 ml of anhydrous dimethylformamide. The mixture is stirred for 1 hour at the same temperature and 0.4 g of isobutyryl chloride is added. The mixture is stirred for 30 minutes at the same temperature and for 1 hour while allowing the temperature to return gradually to 20° C. The insoluble material formed is removed by filtration and the filtrate is concentrated to dryness under reduced pressure (15 mmHg; 2 kPa) at 70° C. The product obtained (1.63 g) is dissolved in 30 ml of methanol and, after addition of decolorizing charcoal, the solution is filtered, diluted with 40 ml of distilled water and stored for 45 minutes at a temperature in the region of 20° C. The insoluble material formed is separated out by filtration, washed with 5 ml of distilled water and with 5 ml of acetone and then dried under reduced pressure (1 mmHg; 0.13 kPa) at 100° C. 0.38 g of 10-isobutyramido-5H,10H-imidazo[1,2-a]indeno[1,2-e]-pyrazin-4-one is thus obtained, decomposing without melting above 260° C. [N.M.R. spectrum: [300 MHz; (CD3)2SO d6 ; δ in ppm]: 1.09 and 1.12 [2d, J=7.5 Hz, 6H: --CH(CH3)2 ]; 2.48 [mt, 1H: --CH(CH3)2 ]; 6.15 (d, J=8.5 Hz, 1H: --CH-- 10); 7.35 and 7.45 (2t broad, J=8.5 Hz, 1H each: --H7 and --H8); 7.47 and 7.85 (2d broad, J=8 Hz, 1H each: --H6 and --H9); 7.52 and 7.58 (2s, 1H each: --H of the imidazole); 8.46 (d, J=8.5 Hz, 1H: --NHCO-- at 10); 12.48 (broad s, 1H: --CONH-- of the ring)].
Reaction SMILES: [CH3:1][C:2]1([CH3:15])[CH:7]=[CH:6][C:5]2[CH:8]=[C:9]([N+:12]([O-])=O)[CH:10]=[CH:11][C:4]=2[O:3]1.O.NN.O>C(O)C.[Pt]>[NH2:12][C:9]1[CH:10]=[CH:11][C:4]2[O:3][C:2]([CH3:1])([CH3:15])[CH:7]=[CH:6][C:5]=2[CH:8]=1
Reactant: CC1(C)C=Cc2cc([N+](=O)[O-])ccc2O1
Agent: [Pt]
Agent: NN
Solvent: O
Solvent: CCO
Product: CC1(C)C=Cc2cc(N)ccc2O1
Temperature: 35 °C
Reaction time: 0.5 h

Procedure:
Ten grams (10 g, 48.7 mmol) of 2,2-dimethyl 6-nitro 2H-1-benzopyran (3) was dissolved in 60.0 g of ethanol under heating. After cooling to 35° C., 0.6 g of 2% Pt—C (50% water-containing product) was added thereto, and 5.85 g (117.0 mmol) of hydrazine monohydrate (98% product) was added dropwise (dropwise adding was continued for 30 minutes) while controlling internal temperature to 40° C. or less. After completion of dropwise adding, reaction was carried out at a temperature of 40 to 45° C. for 6 hours. The resulting solution was cooled to room temperature, and then 10.0 g of water was added thereto and the resulting solution was filtered through celite. The celite was washed with 20.0 g of 80% water-containing ethanol, and the washing together with the filtrate were subjected to solvent-distillation. The residue was extracted with 40.0 g of toluene and 20.0 g of water. After separating into phases, the aqueous phase was extracted with 20.0 g toluene again. The toluene phases were combined, washed with 20.0 g of water and then subjected to solvent-distillation to obtain a crude product of intended product (4).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:11]([CH3:12])=[C:10]2[C:6]([C:7](=[O:13])[O:8][CH2:9]2)=[C:5]([O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[C:4]=1[CH2:21][CH:22]=[C:23]([CH3:26])[CH:24]=[O:25].O.[Li+].[BH4-]>CO.C1COCC1>[OH:25][CH2:24][C:23]([CH3:26])=[CH:22][CH2:21][C:4]1[C:5]([O:14][CH2:15][CH2:16][Si:17]([CH3:18])([CH3:20])[CH3:19])=[C:6]2[C:10]([CH2:9][O:8][C:7]2=[O:13])=[C:11]([CH3:12])[C:3]=1[O:2][CH3:1]
Reactant: COc1c(C)c2c(c(OCC[Si](C)(C)C)c1CC=C(C)C=O)C(=O)OC2
Agent: [BH4-]
Agent: [Li+]
Solvent: CO
Solvent: C1CCOC1
Solvent: O
Product: COc1c(C)c2c(c(OCC[Si](C)(C)C)c1CC=C(C)CO)C(=O)OC2
Temperature: 25 °C
Reaction time: 0.67 h
Yield: 97.8 %

Procedure:
A solution of 4-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-2-methyl-but-2-enal (103 mg, 0.27 mmol) in methanol (5 mL) was cooled to 0° C. A solution of CeC13 (0.68 mL, MeOH: H2O, 9:1) was added, followed by LiBH4 (0.14 mL, 0.28 mmol of a 2M solution in THF). The ice bath was removed and the reaction mixture was allowed to warm to room temperature. The reaction mixture was stirred for an additional 40 minutes whereupon TLC indicated complete consumption of starting aldehyde. The reaction was worked up by addition of aqueous 1N HCl (0.5 mL) and the product was extracted with CH2Cl2. The organic layer was washed with saturated aqueous sodium bicarbonate solution and brine. The organic layer was concentrated under reduced pressure and the residue was purified by silica gel chromatography to provide 100 mg (97%) of the product as a clear liquid. 1H NMR (300 MHz, CDCl3) δ 0.00 (s, 9H), 1.20 (dd, 2H, J=7, 8 Hz), 1.81 (s, 3H), 2.13 (s, 3H), 3.38-3.50 (m, 2H), 3.74 (s, 3H), 3.95 (s, 2H), 4.27 (dd, 2H, J=7, 8 Hz), 5.08 (s, 2H), 5.17-5.44 (m, 1H) ppm.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:11])[CH3:10])=[C:4]([CH3:12])[CH:3]=1.[N+:13]([O-])([OH:15])=[O:14]>O(C(C)=O)C(C)=O>[F:1][C:2]1[CH:7]=[C:6]([N+:13]([O-:15])=[O:14])[C:5]([NH:8][C:9](=[O:11])[CH3:10])=[C:4]([CH3:12])[CH:3]=1
Reactant: O=[N+]([O-])O
Reactant: CC(=O)Nc1ccc(F)cc1C
Solvent: CC(=O)OC(C)=O
Product: CC(=O)Nc1c(C)cc(F)cc1[N+](=O)[O-]
Temperature: 25 °C

Procedure:
To a mixture of N-(4-fluoro-2-methylphenyl)acetamide (19 g, 113.1 mmol, 1 eq) and (CH3CO)2O (190 mL) was added HNO3 (11.4 mL, 1.0 eq) dropwise at 0° C. The reaction mixture was allowed to warm to RT overnight and was subsequently poured onto ice and extracted with DCM. The organic phase was washed with aqueous NaHCO3 until the pH of the aqueous layer was >7. The organic phase was washed with water and then dried over Na2SO4. The solvent was evaporated to give the title compound as a crude solid (20 g, 84%). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.82 (1H, s), 7.71 (1H, dd, J1=2.8 Hz, J2=8.0 Hz), 7.56 (1H, dd, J1=2.8 Hz, J2=9.2 Hz), 2.32 (3H, s), 2.02 (3H, s).
Reaction SMILES: [CH2:1]([C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1[C:18]1[CH:19]=[C:20]([OH:24])[CH:21]=[CH:22][CH:23]=1)=[CH:15][CH:14]=[CH:13][C:12]=2[C:25]([F:28])([F:27])[F:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:29][N:30]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][C:37]=2[CH2:39]O)[CH:32]=[CH:31]1>>[CH2:1]([C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH2:39][C:37]3[CH:36]=[CH:35][CH:34]=[C:33]4[C:38]=3[N:30]([CH3:29])[CH:31]=[CH:32]4)[CH:19]=1)=[CH:15][CH:14]=[CH:13][C:12]=2[C:25]([F:28])([F:26])[F:27])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Oc1cccc(-c2c(Cc3ccccc3)cnc3c(C(F)(F)F)cccc23)c1
Reactant: Cn1ccc2cccc(CO)c21
Product: Cn1ccc2cccc(COc3cccc(-c4c(Cc5ccccc5)cnc5c(C(F)(F)F)cccc45)c3)c21

Procedure:
The title compound was prepared from 3-[3-benzyl-8-(trifluoromethyl)quinolin-4-yl]phenol and (1-methyl-1H-indol-7-yl)-methanol according to the procedure of Example 69. MS (ES) m/z 523.6.
Reaction SMILES: [C:1]([C@H:6]1[O:10][C@H:9](C(=O)C)[CH2:8][O:7]1)([O:3][CH2:4][CH3:5])=[O:2].C1C=C(Cl)C=[C:16]([C:21]([O:23]O)=[O:22])C=1.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl.O>[C:1]([C@H:6]1[O:10][C@H:9]([O:23][C:21](=[O:22])[CH3:16])[CH2:8][O:7]1)([O:3][CH2:4][CH3:5])=[O:2]
Reactant: CCOC(=O)[C@@H]1OC[C@@H](C(C)=O)O1
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Product: CCOC(=O)[C@@H]1OC[C@@H](OC(C)=O)O1
Temperature: 25 °C
Reaction time: 16 h
Yield: 49 %

Procedure:
A 2.5:1 mixture of cis and trans-2-carboethoxy-4-acetyl-1,3-dioxolane (406 mg, 2.16 mmol), 85% mCPBA (68 mg, 3.81 mmol) and sodium carbonate (389 mg, 3.67 mmol) in dry dichloromethane (10 mL) was stirred under argon for 16 hours at room temperature. The resultant suspension was diluted with dichloromethane and water and stirred for 10 minutes. The aqueous phase was removed and the organic phase was washed successively with saturated sodium thiosulfate, water, brine and then was dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the crude product thus obtained was subjected to flash column chromatography (30% EtOAc-Hexanes) to give the title compound (49% yield) which displayed the following spectral characteristics; 1H NMR (CDCl3):δ 1.29 (t, 3H, J=7.2 Hz), 2.09 (s, 1H), 4.12 (d of d, 1H, J=0.9, 9.1 Hz), 4.19-4.31 (m, 3H), 5.53 (s, 1H), 6.48 (d of d, 1H, J=0.9, 3.9 Hz).
Reaction SMILES: O.O.[Sn](Cl)Cl.[CH3:6][O:7][C:8]([C:10]1[S:11][C:12]([Br:18])=[CH:13][C:14]=1[N+:15]([O-])=O)=[O:9]>CO>[CH3:6][O:7][C:8]([C:10]1[S:11][C:12]([Br:18])=[CH:13][C:14]=1[NH2:15])=[O:9]
Reactant: COC(=O)c1sc(Br)cc1[N+](=O)[O-]
Agent: Cl[Sn]Cl
Solvent: O
Solvent: CO
Product: COC(=O)c1sc(Br)cc1N
Temperature: 65 °C
Reaction time: 0.5 h

Procedure:
Tin(II) chloride dihydrate (74.8 g) was added in portions to a solution of 5-bromo-3-nitrothiophene-2-carboxylic acid methyl ester (21.0 g) in methanol (1 L), and the mixture was stirred at 65° C. for 30 min. The mixture was concentrated and 500 mL of ethyl acetate and 700 mL of Rochelle's salt solution were added to the residue. The mixture was vigorously stirred for 1 h. The organic phase was dried over magnesium sulfate and concentrated. The product with the molecular weight of 236.09 (C6H6BrNO2S) was obtained in this way; MS (ESI): 236 (M+H+).
Reaction SMILES: [C:1]1(/[C:7](/[C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)=[CH:8]\[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][OH:14])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:21]1([N:27]=[C:28]=[O:29])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(N(CC)CC)C>C(Cl)Cl>[C:21]1([NH:27][C:28]([O:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]/[CH:8]=[C:7](\[C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)/[C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)=[O:29])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: O=C=Nc1ccccc1
Reactant: OCCCCC/C=C(\c1ccccc1)c1cccnc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(Nc1ccccc1)OCCCCC/C=C(\c1ccccc1)c1cccnc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 55.2 %

Procedure:
(E)-7-Phenyl-7-(3-pyridyl)-6-hepten-1-ol (4 g, 15 mmoles) and phenyl isocyanate (1.6 ml, 15 mmoles) were dissolved in methylene chloride (20 ml), and triethylamine (0.5 ml) was added to the solution. The mixture was stirred at room temperature for 3 hours and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography using isopropyl ether-ethyl acetate (2:1) as the developing solvent and recrystallization of the product from a mixture of ethyl acetate and isopropyl ether gave 1-phenylaminocarbonyloxy-(E)-7-phenyl-7-(3-pyridyl)-6-heptene (3.2 g, 55%)
Reaction SMILES: [SH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([OH:12])=[O:11])=[CH:4][CH:3]=1.C(N(CC)CC)C.Cl[CH2:21][C:22]1[N:23]=[C:24](/[CH:27]=[CH:28]/[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[O:25][CH:26]=1.O>CN(C)C=O>[C:29]1(/[CH:28]=[CH:27]/[C:24]2[O:25][CH:26]=[C:22]([CH2:21][S:1][C:2]3[CH:3]=[CH:4][C:5]([CH2:8][CH2:9][C:10]([OH:12])=[O:11])=[CH:6][CH:7]=3)[N:23]=2)[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1
Reactant: ClCc1coc(/C=C/c2ccccc2)n1
Reactant: O=C(O)CCc1ccc(S)cc1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: O
Product: O=C(O)CCc1ccc(SCc2coc(/C=C/c3ccccc3)n2)cc1
Reaction time: 2.5 h
Yield: 83.3 %

Procedure:
To a solution of 3-(4-mercaptophenyl)propionic acid (2.0 g) and triethylamine (2.23 g) in N,N-dimethylformamide (50 ml) was added dropwise a solution of 4-chloromethyl-2-[(E)-2-phenyl ethenyl]oxazole (2.20 g) in N,N-dimethylformamide (10 ml) at 0° C. and then stirred for 2.5 hours. To the reaction mixture was added water, and extracted with diethyl ether. The water layer was made acidic with concentrated hydrochloric acid, and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried (MgSO4), and concentrated under reduced pressure to give crystals of 3-[4-[2-[(E)-2-phenyl ethenyl]-4-oxazolylmethylthio]phenyl]propionic acid (3.05 g, 84%). Recrystallization from ethyl acetate-hexane gave colorless prisms, mp 120-121° C.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][CH2:5][NH2:6].Br[CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10]>O1CCCC1.O>[CH2:12]([O:11][C:9](=[O:10])[CH2:8][NH:6][CH2:5][CH2:4][CH2:3][O:2][CH3:1])[CH3:13]
Reactant: CCOC(=O)CBr
Reactant: COCCCN
Solvent: C1CCOC1
Solvent: O
Product: CCOC(=O)CNCCCOC
Temperature: 25 °C
Reaction time: 2 h
Yield: 67.1 %

Procedure:
A solution containing 52 g of 3-methoxypropylamine in 100 ml of tetrahydrofuran is immersed in iced water and a solution containing 27 g of ethyl bromoacetate in 30 ml of tetrahydrofuran is added dropwise for 1 hour. The resultant is stirred at room temperature for 2 hours and the solvent and the excess 3-methoxypropylamine are evaporated under reduced pressure. The residue is purified by silica gel column chromatography (ethanol:dichloromethane=1:20) to obtain 19 g of the captioned compound in the form of colorless oil.
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:10]([C:29]([OH:31])=O)=[N:11][C:12]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[N:13][C:14]=1[OH:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Si:32]([O:39][CH2:40][CH2:41][NH:42][CH3:43])([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33].O=P(Cl)(Cl)Cl.O>N1C=CC=CC=1>[Si:32]([O:39][CH2:40][CH2:41][N:42]([CH3:43])[C:29]([C:10]1[C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[C:14]([OH:15])[N:13]=[C:12]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[N:11]=1)=[O:31])([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:33])[CH3:34]
Reactant: CNCCO[Si](C)(C)C(C)(C)C
Reactant: O=C(O)c1nc(Cc2ccccc2-c2ccccc2)nc(O)c1OCc1ccccc1
Solvent: O
Solvent: c1ccncc1
Solvent: O=P(Cl)(Cl)Cl
Product: CN(CCO[Si](C)(C)C(C)(C)C)C(=O)c1nc(Cc2ccccc2-c2ccccc2)nc(O)c1OCc1ccccc1
Temperature: 0 °C
Reaction time: 2 h
Yield: 49.4 %

Procedure:
To a stirred solution of 5-benzyloxy-2-biphenyl-2-ylmethyl-6-hydroxypyrimidine-4-carboxylic acid (7-01) (3 g, 7.28 mmol) and [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-methyl-amine (8-a) (1.51 g, 8.01 mmol) in pyridine (40 mL) was added POCl3 (2 ml, 21.84 mol) at −10° C. The mixture was stirred at 0° C. for 2 h. After completion of the reaction, ice cooled-water (30 mL) was added to the reaction mixture at 0° C. The mixture was extracted with ethyl acetate (4×200 mL). The separated organic part was washed with saturated aqueous solution of NaHCO3, dried and concentrated to get a crude product which was purified by normal silica column using 40% ethyl acetate in hexane to get 5-benzyloxy-2-biphenyl-2-ylmethyl-6-hydroxypyrimidine-4-carboxylic acid [2-(tert-butyl-dimethylsilanyloxy)-ethyl]methyl-amide (9-01) (2.1 g, 49.4%) as a yellow sticky mass.
Reaction SMILES: [NH2:1][C:2]1[N:3]=[C:4]2[N:13]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=3)[CH2:12][CH2:11][N:5]2[C:6](=[O:10])[C:7]=1[N:8]=O.S(S([O-])(=O)=O)([O-])(=O)=O.[Na+].[Na+].O.[OH-].[Na+].[CH4:35]>C(O)=O>[Cl:21][C:18]1[CH:19]=[CH:20][C:15]([CH2:14][N:13]2[C:4]3=[N:3][C:2]4[NH:1][CH:35]=[N:8][C:7]=4[C:6](=[O:10])[N:5]3[CH2:11][CH2:12]2)=[CH:16][CH:17]=1
Reactant: C
Reactant: Nc1nc2n(c(=O)c1N=O)CCN2Cc1ccc(Cl)cc1
Agent: O=S(=O)([O-])S(=O)(=O)[O-]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: O=CO
Product: O=c1c2nc[nH]c2nc2n1CCN2Cc1ccc(Cl)cc1

Procedure:
The nitroso compound of Procedure 92 was reduced with sodium dithionate in formic acid according to the method of Procedure 21. The resulting 6-formylamino compound, 1.3 g. (0.0041 mole), was suspended in 40 ml. of water containing 0.0043 mole of NaOH and the mixture was heated on the steam bath until dissolution occurred. The solution was treated with charcoal, filtered, cooled and acidified with HOAc to yield the desired product, 0.85 g., recrystallized from MeOH, yield 0.60 g., hemihydrate m.p. 314°-316° d.