Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1](Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:9][C:10]([C:16]([F:19])([F:18])[F:17])([S-:15])[C:11]([F:14])([F:13])[F:12].CN([S+](N(C)C)N(C)C)C>C(#N)C>[F:12][C:11]([F:13])([F:14])[C:10]([S:15][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)([F:9])[C:16]([F:19])([F:18])[F:17]
Reactant: BrCc1ccccc1
Reactant: FC(F)(F)C(F)([S-])C(F)(F)F
Agent: CN(C)[S+](N(C)C)N(C)C
Solvent: CC#N
Product: FC(F)(F)C(F)(SCc1ccccc1)C(F)(F)F
Temperature: 0 °C
Reaction time: 18 h
Yield: 75 %

Procedure:
Benzyl bromide, 16.76 g (0.098 mol), was added dropwise at 25° to a solution of 0.098 mole of tris(dimethylamino)sulfonium 1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethanethiolate (prepared as in Example 12) in 125 mL of acetonitrile. The reaction mixture was stirred for 18 h and then poured into 500 mL of ice-water. The aqueous mixture was extracted with ether, and the ether extracts were washed with water, dried (MgSO4) and distilled to give 21.31 g (75% yield) of benzyl heptafluoroisopropyl sulfide as a pale yellow liquid: bp 70°-71° (10 mm); 1H NMR (CDCl3) δ4.09 ppm (s, 2H) and 7.27 ppm (s, 5H); 19F NMR (CDCl3) δ-75.2 ppm (d, J=11 Hz, 6F) and -162.6 ppm (septet, J=11 Hz, 1F). Anal. Calcd. for C10H7F7S: C, 41.10; H, 2.41; F, 45.51. Found: C, 40.89; H, 2.45; F, 45.27.
Reaction SMILES: CN(C)C=O.N1CCCCC1.C1(NC(N2C3C(=CC(OC4C=CN=C(NC(=O)OC5C=CC=CC=5)C=4)=CC=3)C=C2)=O)CC1.[CH:44]1([NH:47][C:48]([N:50]2[C:58]3[C:53](=[CH:54][C:55]([O:59][C:60]4[CH:65]=[CH:64][N:63]=[C:62]([NH:66][C:67]([N:69]5[CH2:74][CH2:73][CH:72](N6CCCC6)[CH2:71][CH2:70]5)=[O:68])[CH:61]=4)=[CH:56][CH:57]=3)[CH:52]=[CH:51]2)=[O:49])[CH2:46][CH2:45]1>C(OCC)C>[CH:44]1([NH:47][C:48]([N:50]2[C:58]3[C:53](=[CH:54][C:55]([O:59][C:60]4[CH:65]=[CH:64][N:63]=[C:62]([NH:66][C:67]([N:69]5[CH2:74][CH2:73][CH2:72][CH2:71][CH2:70]5)=[O:68])[CH:61]=4)=[CH:56][CH:57]=3)[CH:52]=[CH:51]2)=[O:49])[CH2:46][CH2:45]1
Reactant: O=C(Nc1cc(Oc2ccc3c(ccn3C(=O)NC3CC3)c2)ccn1)N1CCC(N2CCCC2)CC1
Agent: O=C(Nc1cc(Oc2ccc3c(ccn3C(=O)NC3CC3)c2)ccn1)Oc1ccccc1
Solvent: C1CCNCC1
Solvent: CCOCC
Solvent: CN(C)C=O
Product: O=C(Nc1cc(Oc2ccc3c(ccn3C(=O)NC3CC3)c2)ccn1)N1CCCCC1
Reaction time: 8 h

Procedure:
N,N-Dimethylformamide (5 ml) and piperidine (0.42 ml, 4.2 mmol) were added to a mixture (467 mg) of phenyl N-(4-(1-cyclopropylaminocarbonyl-1H-5-indolyl)oxy-2-pyridyl)carbamate and phenyl N-(4-(1-cyclopropylaminocarbonyl-1H-5-indolyl)oxy-2-pyridyl)-N-(phenoxycarbonyl)carbamate obtained in Example 68; and the reaction mixture was stirred overnight; the reaction mixture was partitioned between ethyl acetate and water; the organic layer was concentrated; the obtained solid was washed with a solvent mixture of hexane:diethyl ether=1:1 to yield the title compound as crystals (241 mg, 0.57 mmol).
Reaction SMILES: [O:1]1[C:5]2[CH2:6][NH:7][CH2:8][CH:9]([OH:10])[C:4]=2[CH:3]=[CH:2]1.F[C:12]1[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=1>>[F:19][C:18]([F:21])([F:20])[C:15]1[CH:16]=[CH:17][C:12]([O:10][CH:9]2[CH2:8][NH:7][CH2:6][C:5]3[O:1][CH:2]=[CH:3][C:4]2=3)=[CH:13][CH:14]=1
Reactant: Fc1ccc(C(F)(F)F)cc1
Reactant: OC1CNCc2occc21
Product: FC(F)(F)c1ccc(OC2CNCc3occc32)cc1

Procedure:
The same method as in Example 1 was conducted using 4,5,6,7-tetrahydrofuro[2,3-c]pyridin-4-ol (Reference Example 4) instead of 6-methyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-4-ol (Reference Example 6) and was conducted using 4-fluorobenzotrifluoride instead of 1-fluoronaphthalene to give the objective compound.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:20]([C:22]3[O:23][C:24](=[O:39])[C:25]4[C:30]([C:31]=3[CH2:32][N:33]3[CH2:38][CH2:37][O:36][CH2:35][CH2:34]3)=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH3:21])[N:9]=[C:10]([C:11]3[CH:16]=[C:15]([O:17]C)[CH:14]=[C:13]([F:19])[CH:12]=3)[C:3]=12.C(O)C>C(Cl)Cl.B(Br)(Br)Br>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:20]([C:22]3[O:23][C:24](=[O:39])[C:25]4[C:30]([C:31]=3[CH2:32][N:33]3[CH2:34][CH2:35][O:36][CH2:37][CH2:38]3)=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH3:21])[N:9]=[C:10]([C:11]3[CH:16]=[C:15]([OH:17])[CH:14]=[C:13]([F:19])[CH:12]=3)[C:3]=12
Reactant: COc1cc(F)cc(-c2nn(C(C)c3oc(=O)c4ccccc4c3CN3CCOCC3)c3ncnc(N)c23)c1
Agent: BrB(Br)Br
Solvent: CCO
Solvent: ClCCl
Product: CC(c1oc(=O)c2ccccc2c1CN1CCOCC1)n1nc(-c2cc(O)cc(F)c2)c2c(N)ncnc21
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 15.6 %

Procedure:
To a solution of 3-(1-(4-amino-3-(3-fluoro-5-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(morpholinomethyl)-1H-isochromen-1-one (0.033 g) in dry DCM (2 ml), 1M BBr3 in DCM (0.93 ml, 0.93 mmol) was added and the solution was stirred at room temperature for 2.5 hrs. The solution was cooled to 0° C. and ethanol (8 ml) was added. The solution was evaporate to dryness and crude was purified by flash chromatography in silica-NH cartridge (DCM to DCM:MeOH=90:10) affording title compound as a pale orange solid (5 mg).
Reaction SMILES: [CH3:1][C:2]1[N:7]=[C:6]([C:8]#[C:9][CH:10]=[C:11]2[CH2:16][CH2:15][N:14]([C:17]3[C:26]4[C:21](=CC=CC=4)[CH:20]=[N:19][CH:18]=3)[CH2:13][CH2:12]2)[CH:5]=[CH:4][CH:3]=1.BrC1C=[CH:30][C:31]([O:34]CC)=NC=1.C1(C)C=CC(P(C2C=CC(C)=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC(C)=CC=2)C2C=CC(C)=CC=2)=CC=1>>[CH2:31]([O:34][C:20]1[CH:21]=[CH:26][C:17]([N:14]2[CH2:13][CH2:12][C:11](=[CH:10][C:9]#[C:8][C:6]3[CH:5]=[CH:4][CH:3]=[C:2]([CH3:1])[N:7]=3)[CH2:16][CH2:15]2)=[CH:18][N:19]=1)[CH3:30]
Reactant: Cc1cccc(C#CC=C2CCN(c3cncc4ccccc34)CC2)n1
Reactant: CCOc1ccc(Br)cn1
Agent: Cc1ccc(P(c2ccc(C)cc2)c2ccc3ccccc3c2-c2c(P(c3ccc(C)cc3)c3ccc(C)cc3)ccc3ccccc23)cc1
Product: CCOc1ccc(N2CCC(=CC#Cc3cccc(C)n3)CC2)cn1
Yield: 10 %

Procedure:
Following the procedure reported for the compound of Example 234 and using 5-bromo-2-ethoxypyridine instead of 4-bromoisoquinoline and tol-BINAP (2,2′-bis(di-p-tolylphosphino)-1,1′-binaphthyl) instead of BINAP the title compound was prepared. After the work-up, the residue was purified by automated flash liquid chromatography (Horizon™-Biotage) eluting with PE-EtOAc 8:2. affording the title product as a yellow oil. Yield: 10%.
Reaction SMILES: [CH3:1][CH:2]1[N:7]([CH3:8])[CH2:6][CH2:5][N:4]([C:9]2[CH:18]=[CH:17][C:12]([C:13]([O:15]C)=O)=[CH:11][CH:10]=2)[CH2:3]1.[NH2:19][C:20]1[N:24](C(OC(C)(C)C)=O)[N:23]=[C:22]([CH2:32][CH2:33][C:34]2[CH:39]=[C:38]([O:40][CH3:41])[CH:37]=[C:36]([O:42][CH3:43])[CH:35]=2)[CH:21]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1>[CH3:41][O:40][C:38]1[CH:39]=[C:34]([CH2:33][CH2:32][C:22]2[NH:23][N:24]=[C:20]([NH:19][C:13](=[O:15])[C:12]3[CH:11]=[CH:10][C:9]([N:4]4[CH2:5][CH2:6][N:7]([CH3:8])[CH:2]([CH3:1])[CH2:3]4)=[CH:18][CH:17]=3)[CH:21]=2)[CH:35]=[C:36]([O:42][CH3:43])[CH:37]=1
Reactant: COc1cc(CCc2cc(N)n(C(=O)OC(C)(C)C)n2)cc(OC)c1
Reactant: COC(=O)c1ccc(N2CCN(C)C(C)C2)cc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Na+]
Solvent: C1CCOC1
Product: COc1cc(CCc2cc(NC(=O)c3ccc(N4CCN(C)C(C)C4)cc3)n[nH]2)cc(OC)c1
Yield: 19.4 %

Procedure:
N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-yl]-4-(3,4-dimethylpiperazin-1-yl)benzamide was prepared as for Example 94, but starting from methyl 4-(3,4-dimethylpiperazin-1-yl)benzoate (221 mg, 0.84 mmol), tert-butyl 5-amino-3-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazole-1-carboxylate (244 mg, 0.7 mmol) and 1M NaHMDS (1.13 ml, 1.13 mmol) in THF (5 ml). The crude product was purified by reverse phase prep. HPLC (basic) using a 38-58% gradient of acetonitrile in water containing 1% 0.880 ammonium hydroxide. The clean fractions were taken and evaporated to afford the title compound as a white solid (63 mg, 19%); 1H NMR (500.13 MHz, DMSO-d6) δ 1.12 (3H, d), 1.89-1.90 (3H, m), 2.32 (3H, s), 2.35-2.40 (1H, m), 2.64-2.68 (1H, m), 2.86-2.91 (1H, m), 2.89 (4H, t), 3.00 (1H, s), 3.64-3.68 (2H, m), 3.74 (6H, s), 6.32 (1H, s), 6.33 (1H, t), 6.42 (2H, d), 6.94-6.96 (2H, m), 7.86-7.88 (2H, m). MS: m/z 464 (MH+).
Reaction SMILES: N12CCCCC1C=NCCC2.[CH2:12]([N:19]([CH2:26][S:27]([C:30]([CH3:33])([CH3:32])[CH3:31])(=[O:29])=[O:28])[C:20](=[O:25])[C@@H:21](Br)[CH2:22][OH:23])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(Cl)Cl.P([O-])([O-])([O-])=O>O1CCCC1>[CH2:12]([N:19]([CH2:26][S:27]([C:30]([CH3:33])([CH3:32])[CH3:31])(=[O:29])=[O:28])[C:20](=[O:25])[C@@H:21]1[O:23][CH2:22]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: CC(C)(C)S(=O)(=O)CN(Cc1ccccc1)C(=O)[C@@H](Br)CO
Agent: C1=NCCCN2CCCCC12
Agent: O=P([O-])([O-])[O-]
Solvent: ClCCl
Solvent: C1CCOC1
Product: CC(C)(C)S(=O)(=O)CN(Cc1ccccc1)C(=O)[C@H]1CO1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
1.125 g (7.4 mmol) of 1,5-diazabicyclo[5.4.0]undec-5-ene are added at 0° to a solution of 118 g (3 mmol) of N-benzyl-N-tert.-butylsulphonylmethyl-2-(S)-bromo-3-hydroxypropionic acid amide (see Example 4) in 15 ml of absolute tetrahydrofuran and the whole is stirred for a further 90 minutes at room temperature. After working up with methylene chloride and phosphate buffer having a pH of 7.0, the crude product obtained from the organic phase is chromatographed over 50 g of silica gel. After eluting with a mixture of ethyl acetate/toluene (1:1), the pure title compound, identical to the compound according to Example 6, is obtained.
Reaction SMILES: [CH:1]1([CH2:8]O)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(Br)(Br)(Br)[Br:11]>>[Br:11][CH2:8][CH:1]1[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: BrC(Br)(Br)Br
Reactant: OCC1CCCCCC1
Product: BrCC1CCCCCC1

Procedure:
The subtitle compound was prepared by the method of Preparation 9 from cycloheptylmethanol and carbon tetrabromide. The crude product was purified by fractional distillation, b.pt. 115° C.-120° C. @ 30mmHg to afford 1-(bromomethyl)cycloheptane as an oil.
Reaction SMILES: Cl[CH2:2][SiH2:3][CH:4]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)[C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=1.[Na].[CH3:20][C:21]1[N:25]=[C:24]([CH3:26])[NH:23][N:22]=1>>[CH3:20][C:21]1[N:25]=[C:24]([CH3:26])[N:23]([CH2:2][SiH2:3][CH:4]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[C:5]2[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=2)[N:22]=1
Reactant: Fc1ccc(C([SiH2]CCl)c2ccc(F)cc2)cc1
Reactant: Cc1n[nH]c(C)n1
Agent: [Na]
Product: Cc1nc(C)n(C[SiH2]C(c2ccc(F)cc2)c2ccc(F)cc2)n1

Procedure:
The title compound is prepared by applying the procedure of Example 30 to equimolar quantities of chloromethyl[bis(4-fluorophenyl)]methylsilane and 3,5-dimethyl-1,2,4-triazole sodium salt.
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:25]#[N:26])=[C:4]([C:16]2[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=2[O:23][CH3:24])[C:5]2[C:10](=[O:11])[N:9]([CH3:12])[C:8](=[O:13])[N:7]([CH3:14])[C:6]=2[N:15]=1.[CH2:27]([O:34][C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([CH2:41]Br)[CH:36]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.NCC1C(NCC2C=CC3C(=CC=CC=3)C=2)=NC2N(C)C(=O)N(C)C(=O)C=2C=1C1C=C(F)C=CC=1OC>>[NH2:26][CH2:25][C:3]1[C:2]([NH:1][CH2:41][C:37]2[CH:38]=[CH:39][CH:40]=[C:35]([O:34][CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH:36]=2)=[N:15][C:6]2[N:7]([CH3:14])[C:8](=[O:13])[N:9]([CH3:12])[C:10](=[O:11])[C:5]=2[C:4]=1[C:16]1[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=1[O:23][CH3:24]
Reactant: COc1ccc(F)cc1-c1c(C#N)c(N)nc2c1c(=O)n(C)c(=O)n2C
Reactant: BrCc1cccc(OCc2ccccc2)c1
Agent: COc1ccc(F)cc1-c1c(CN)c(NCc2ccc3ccccc3c2)nc2c1c(=O)n(C)c(=O)n2C
Product: COc1ccc(F)cc1-c1c(CN)c(NCc2cccc(OCc3ccccc3)c2)nc2c1c(=O)n(C)c(=O)n2C

Procedure:
The synthesis of title compounds started from Compound 70a and 1-(benzyloxy)-3-(bromomethyl)benzene, according to procedures described in the synthesis of Compound 70. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 3.25 (s, 3H) 3.54 (s, 3H) 3.74 (s, 3H) 3.76 (d, J=14.4 Hz, 1H) 3.86 (d, J=14.4 Hz, 1H) 4.73 (q, J=15.2 Hz, 2H) 5.06 (s, 1H) 6.72-6.77 (dd, J=3.1, 16.6 Hz 1H) 6.88 (d, J=8.3 Hz 1H) 7.00-7.07 (m, 3H) 7.11-7.19 (m, 1H) 7.25 (t, J=7.8 Hz, 1H) 7.29-7.33 (m, 1H) 7.33-7.44 (m, 5H). MS [m+H] calc'd C31H31FN5O4 556; found 556.
Reaction SMILES: C([C:3]([CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)([C:7](O)=O)[C:4]([OH:6])=[O:5])C.N1CCC[CH2:20][CH2:19]1.C=O>N1C=CC=CC=1>[CH2:7]=[C:3]([CH2:10][CH2:11][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)[C:4]([O:6][CH2:19][CH3:20])=[O:5]
Reactant: C1CCNCC1
Reactant: CCC(CCc1ccccc1)(C(=O)O)C(=O)O
Agent: C=O
Solvent: c1ccncc1
Product: C=C(CCc1ccccc1)C(=O)OCC
Yield: 89 %

Procedure:
Monoethyl 2-[2-(phenyl)ethyl]malonic acid (47.2 g, 200 mole) was added to 40 mL of pyridine in a 250 mL round bottomed flask fitted with a Teflon coated stirring bar. Piperidine (3 mL) and paraformaldehyde (8.4 g, 280 mmole) were added to the flask and the flask was heated to 55°-60° C. until gas evolution ceased. TLC indicated that no starting material remained. The solution was worked up by removing the solvent under reduced pressure. Water (50 mL ) and enough 12N HCl was added to the flask to acidify the mixture (pH<3). The mixture was extracted with ether (3×50 mL) and back extracted with brine. The solution was dried over MgSO4 and filtered. The reaction mixture was shown to be clean by NMR and TLC and used without further purification. Recovered 36.3 g material (89% yield).
Reaction SMILES: [F:1][CH2:2][C:3]1([S:6]([NH:9]C(=O)OC(C)(C)C)(=[O:8])=[O:7])[CH2:5][CH2:4]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:1][CH2:2][C:3]1([S:6]([NH2:9])(=[O:8])=[O:7])[CH2:5][CH2:4]1
Reactant: CC(C)(C)OC(=O)NS(=O)(=O)C1(CF)CC1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: NS(=O)(=O)C1(CF)CC1
Reaction time: 2 h
Yield: 101.2 %

Procedure:
To a solution of tert-butyl (1-(fluoromethyl)cyclopropyl)sulfonylcarbamate (19.8 g, 38.7 mmol) in DCM (100 ml) was added TFA (30 ml, 387 mmol) drop wise at room temperature. The reaction mass was stirred for 2 hr. The reaction mass was evaporated under reduced pressure to get desired compound (6 g, 100%) as off white solid. 1H NMR (400 MHz, CDCl3): δ ppm 4.78-4.66 (d, J=48 Hz, 2H), 2.61 (br, s, 1H), 1.59-1.56 (m, 2H), 1.13-1.10 (m, 2H).
Reaction SMILES: [C:1]([C:3]1[CH:4]=[CH:5][C:6]([F:19])=[C:7]2[C:11]=1[NH:10][CH:9]=[C:8]2/[CH:12]=[CH:13]/[C:14]([O:16][CH2:17][CH3:18])=[O:15])#[N:2]>C1COCC1.[Pd]>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([F:19])=[C:7]2[C:11]=1[NH:10][CH:9]=[C:8]2[CH2:12][CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])#[N:2]
Reactant: CCOC(=O)/C=C/c1c[nH]c2c(C#N)ccc(F)c12
Agent: [Pd]
Solvent: C1CCOC1
Product: CCOC(=O)CCc1c[nH]c2c(C#N)ccc(F)c12
Reaction time: 6 h
Yield: 59.5 %

Procedure:
A solution of ethyl (2E)-3-(7-cyano-4-fluoro-1H-indol-3-yl)-2-propenoate (D43) (10.0 g) in THF (100 mL) under H2 (30 psi) atmosphere was hydrogenated by using the catalyst of Pd/C (with 50% water, 3.0 g). The reaction was stirred for about 6 hours. TLC showed the starting material was completely consumed. Then Pd/C was removed by filtration. The filtrate was concentrated. The residue was purified by column chromatography on silical gel to afford ethyl 3-(7-cyano-4-fluoro-1H-indol-3-yl)propanoate (D44) (6.0 g) as a white solid. δH (CDCl3, 400 MHz): 1.25 (3H, t), 2.72 (2H, t), 3.18 (2H, t), 4.14 (2H, q), 6.82 (1H, t), 7.10 (1H, s), 7.45 (1H, q), 8.88 (1H, s). MS (ES): C14H13FN2O2 requires 260; found 261.1 (M+H+).
Reaction SMILES: [CH2:1]([C@:3]12[CH2:11][CH2:10][C@@H:9]3[C:12]4[CH2:13][CH:14]=[C:15]([O:20]C)[CH2:16][C:17]=4[CH2:18][CH2:19][C@H:8]3[C@@H:7]1[CH2:6][CH2:5][C@@H:4]2[OH:22])[CH3:2].O>CO.Cl>[CH2:1]([C@:3]12[CH2:11][CH2:10][C@@H:9]3[C@@H:12]4[C:17]([CH2:18][CH2:19][C@H:8]3[C@@H:7]1[CH2:6][CH2:5][C@@H:4]2[OH:22])=[CH:16][C:15](=[O:20])[CH2:14][CH2:13]4)[CH3:2]
Reactant: CC[C@]12CC[C@@H]3C4=C(CC[C@H]3[C@@H]1CC[C@@H]2O)CC(OC)=CC4
Agent: Cl
Solvent: O
Solvent: CO
Product: CC[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)CC[C@@H]43)[C@@H]1CC[C@@H]2O
Reaction time: 2 h
Yield: 52.4 %

Procedure:
Add to 13β-ethyl-3-methoxy-gona-2,5(10)-dien-17β-ol (1.0 g.) in methanol (50 cc.), 3N hydrochloric acid (20 cc.); shake the mixture for 2 hours, pour into water, and extract the product with ether. Work up in the usual way and take up the resulting gum in benzene and chromatograph on neutral alumina. Elute with ether to give a crystalline material and recrystallize from a mixture of ether and pentane to yield 13β-ethyl-17β-hydroxy-gon-4-en-3-one (0.5 g.), m.p. 144°-7°; ultra-violet absorption peak at 240 mμ (ε15,500); infrared absorption peaks at 2.94, 6.06, 6.23 μ.
Reaction SMILES: [CH:1]1[C:6]2[C:7]3[O:8][C:9]4[C:14]([C:15]=3[NH:16][C:17](=[O:18])[C:5]=2[CH:4]=[CH:3][CH:2]=1)=[CH:13][CH:12]=[CH:11][CH:10]=4.[C:19](OC(=O)C)(=[O:21])[CH3:20]>N1C=CC=CC=1>[CH:1]1[C:6]2=[C:7]3[C:15](=[N:16][C:17]([O:18][C:19](=[O:21])[CH3:20])=[C:5]2[CH:4]=[CH:3][CH:2]=1)[C:14]1[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=1)[O:8]3
Reactant: O=c1[nH]c2c3ccccc3oc2c2ccccc12
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: CC(=O)Oc1nc2c3ccccc3oc2c2ccccc12
Temperature: 25 °C
Yield: 52 %

Procedure:
To a solution of compound 15c (500 mg, 2.13 mmol) in pyridine (10 mL) was added acetic anhydride (4 mL). The resultant mixture was heated at 100° C. for 9 h, then cooled slowly to room temperature overnight. The solvent was removed on the rotary evaporator and the residual oil was extracted into 50 mL ethyl acetate. The organic layer was washed with 50 mL of 1 N aqueous hydrochloric acid, dried (sodium sulfate), and the solvent removed in vacuo to provide 308 mg (52% yield) of compound 16g as a white powder.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([N:6]=[C:7]([OH:13])[C:8]([OH:12])=[N:9]2)=[C:4]([N+:14]([O-:16])=[O:15])[C:3]=1[NH:17]C(OCC)=O.[OH-].[K+].CCOCC>COCCO>[NH2:17][C:3]1[C:4]([N+:14]([O-:16])=[O:15])=[C:5]2[C:10](=[CH:11][C:2]=1[Cl:1])[N:9]=[C:8]([OH:12])[C:7]([OH:13])=[N:6]2
Reactant: CCOC(=O)Nc1c(Cl)cc2nc(O)c(O)nc2c1[N+](=O)[O-]
Agent: [K+]
Agent: [OH-]
Solvent: COCCO
Solvent: CCOCC
Product: Nc1c(Cl)cc2nc(O)c(O)nc2c1[N+](=O)[O-]
Temperature: 25 °C
Yield: 86 %

Procedure:
A mixture of 5 g (15,4 mmol) 7-chloro-6-ethoxycarbonylamino-5-nitro-2,3-dihydroxyquinoxaline and 10 g potassium hydroxide in 60 ml 2-methoxyethanol was refluxed for 15 min. After cooling to 25° C., the reaction mixture was added 20 ml 2-methoxyethanol and 40 ml ether. The precipitated black product was filtered off and washed with ether. The crude product was dissolved in 100 ml water. Addition of 4N hydrochloric acid to pH 5-6 gave 3,4 g (87%) 6-amino-7-chloro-5-nitro-2,3-dihydroxyquinoxaline as red crystals, m.p.>300° C. NMR (DMSO-d6) 12.3 (2H, broad m), 7.40 (1H,s), 6.8 (2H, broad s).
Reaction SMILES: P([O-])([O-])([O-])=[O:2].[OH:6][C@H:7]([CH2:59][CH2:60][O:61][C:62]1[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=1)[CH2:8][C:9](SCCNC(=O)CCNC(=O)[C@H](O)C(C)(C)COP(O)(=O)OP(O)(=O)OC[C@H]1O[C@@H](N2C3N=CN=C(N)C=3N=C2)[C@H](O)[C@@H]1OP(O)(O)=O)=[O:10]>>[OH:6][CH:7]([CH2:59][CH2:60][O:61][C:62]1[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=1)[CH2:8][C:9]([OH:10])=[O:2]
Reactant: O=P([O-])([O-])[O-]
Reactant: CC(C)(COP(=O)(O)OP(=O)(O)OC[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H]1OP(=O)(O)O)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C[C@H](O)CCOc1ccccc1
Product: O=C(O)CC(O)CCOc1ccccc1

Procedure:
Then, the pellet was suspended in 480 parts of a 0.1M phosphate buffer (pH 7.0), and 5 parts of (R)-3-hydroxy-5-phenoxyvaleryl CoA (prepared by a method described in Eur. J. Biochem., 250, 432–439 (1997) after obtaining 3-hydroxy-5-phenoxyvaleric acid by hydrolyzing 3-hydroxy-5-phenoxylvaleric acid ester obtained by a Reformatsky reaction using zinc, in which 3-phenoxypropanal synthesized by a method described in J. Org. Chem., 55, 1490–1492 (1990) and ethyl bromoacetate were used as raw materials) and one part of bovine serum albumin (Sigma) were added to the suspension before moderately shaking the suspension for 30 minutes at 30° C.
Reaction SMILES: [CH:1]([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]2[C:21]([O:32]CC3C=CC(F)=CC=3)=[C:22]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH:23]=[CH:24][CH:25]=2)[N: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>C(O)C.[Pd]>[CH:1]([C:14]1[N:15]=[C:16]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[C:21]=2[OH:32])[CH:17]=[CH:18][CH:19]=1)([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Fc1ccc(COc2c(-c3ccccc3)cccc2-c2cccc(C(c3ccccc3)c3ccccc3)n2)cc1
Agent: [Pd]
Solvent: CCO
Product: Oc1c(-c2ccccc2)cccc1-c1cccc(C(c2ccccc2)c2ccccc2)n1
Reaction time: 24 h
Yield: 45 %

Procedure:
Compound 6 (1.1 g, 2.1 mmol, 1.0 equiv) was dissolved in ethanol (60 mL) and 10% palladium (50% aqueous) on carbon (0.3 g) was added. The material was shaken on a Parr hydrogenator under a hydrogen atmosphere (30 psi) for 24 hr. The reaction was filtered through a layer of Celite and rinsed with dichloromethane (100 mL). The product was absorbed onto silica gel (3 g) by concentration under reduced pressure. This material was purified on a silica gel column (20 g) by eluting with ethyl acetate (2%) in heptanes (600 mL). The desired product was isolated pure in 45% yield (0.39 g).
Reaction SMILES: [ClH:1].[CH:2]1[C:16]2=[C:17]3[C:9]([C:10]4[C:15]2=[CH:14][CH:13]=[CH:12][CH:11]=4)=[CH:8][CH:7]=[CH:6][C:5]3=[C:4]([CH2:18][NH:19][C:20]([CH3:25])([CH2:23]O)[CH2:21][OH:22])[CH:3]=1.C1C2=C3C(C4C2=CC=CC=4)=CC=CC3=C(C=O)C=1.CC(N)(C)CO>CO.CCOCC>[ClH:1].[CH:2]1[C:16]2=[C:17]3[C:9]([C:10]4[C:15]2=[CH:14][CH:13]=[CH:12][CH:11]=4)=[CH:8][CH:7]=[CH:6][C:5]3=[C:4]([CH2:18][NH:19][C:20]([CH3:25])([CH3:23])[CH2:21][OH:22])[CH:3]=1
Reactant: CC(CO)(CO)NCc1ccc2c3c(cccc13)-c1ccccc1-2
Agent: CC(C)(N)CO
Agent: Cl
Agent: O=Cc1ccc2c3c(cccc13)-c1ccccc1-2
Solvent: CCOCC
Solvent: CO
Product: CC(C)(CO)NCc1ccc2c3c(cccc13)-c1ccccc1-2

Procedure:
Using the reductive amination procedure outlined in 1D, 3-fluoranthenecarbaldehyde (1A) and 2-methyl-2-aminopropanol (Aldrich) gave 2-((3-fluoranthenylmethyl)-amino)-2-methyl-1-propanol hydrochloride, mp 288°-290° (dec), (CH3OH/Et2O), (C, H, Cl, N).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C@H:14]2[S:18][C@H:17]([C:19]3[CH:24]=[C:23]([O:25][CH3:26])[C:22]([O:27][CH3:28])=[C:21]([O:29][CH3:30])[CH:20]=3)[CH2:16][S:15]2)[CH:6]=[C:7]([N+:11]([O-])=O)[C:8]=1[O:9][CH3:10].[Cl-].[Ca+2].[Cl-]>C(O)C.O.[Zn]>[NH2:11][C:7]1[C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=[C:5]([C@H:14]2[S:18][C@H:17]([C:19]3[CH:24]=[C:23]([O:25][CH3:26])[C:22]([O:27][CH3:28])=[C:21]([O:29][CH3:30])[CH:20]=3)[CH2:16][S:15]2)[CH:6]=1
Reactant: COc1cc([C@@H]2CS[C@@H](c3cc(OC)c(OC)c([N+](=O)[O-])c3)S2)cc(OC)c1OC
Agent: [Ca+2]
Agent: [Cl-]
Agent: [Zn]
Solvent: O
Solvent: CCO
Product: COc1cc([C@@H]2SC[C@@H](c3cc(OC)c(OC)c(OC)c3)S2)cc(N)c1OC

Procedure:
Trans-2-(3,4-dimethoxy-5-nitrophenyl)-4-(3,4,5-trimethoxyphenyl)-1,3-dithiolane (2) (FIG. 20) (3.10 g, 6.84 mmole) was predissolved in 33 ml absolute ethanol. To this solution was added calcium chloride (0.721 g, 6.50 mmole) predissolved in 7 ml H2O followed by freshly activated zinc dust (10.0 g,195 mmole). The reaction was refluxed for 12 hours. The solid was removed by vacuum filtration through celite and was washed with ethyl acetate. The filtrate was washed with H2O, dried over MgSO4, and evaporated in vacuo to a white foam (2.52 g, 87%).