Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:8][C:9]1[CH:14]=[C:13]([O:15]CC2C=CC=CC=2)[C:12]([CH:23]([CH3:25])[CH3:24])=[CH:11][C:10]=1[C:26]1[N:27]([C:32]2[CH:37]=[CH:36][C:35]([N:38]3[CH2:43][CH2:42][O:41][CH2:40][CH2:39]3)=[CH:34][CH:33]=2)[C:28]([OH:31])=[N:29][N:30]=1)C1C=CC=CC=1.C(O)(=O)C.CN(C)C=O>CO.[C].[Pd]>[OH:31][C:28]1[N:27]([C:32]2[CH:33]=[CH:34][C:35]([N:38]3[CH2:43][CH2:42][O:41][CH2:40][CH2:39]3)=[CH:36][CH:37]=2)[C:26]([C:10]2[CH:11]=[C:12]([CH:23]([CH3:25])[CH3:24])[C:13]([OH:15])=[CH:14][C:9]=2[OH:8])=[N:30][N:29]=1
Reactant: CC(C)c1cc(-c2nnc(O)n2-c2ccc(N3CCOCC3)cc2)c(OCc2ccccc2)cc1OCc1ccccc1
Agent: [Pd]
Solvent: CO
Solvent: CN(C)C=O
Solvent: CC(=O)O
Product: CC(C)c1cc(-c2nnc(O)n2-c2ccc(N3CCOCC3)cc2)c(O)cc1O
Reaction time: 1 h
Yield: 59.6 %

Procedure:
5-(2,4-bis-benzyloxy-5-isopropyl-phenyl)-4-(4-morpholin-4-yl-phenyl)-4H-[1,2,4]triazol-3-ol (1.2 g, 2.07 mmol) was suspended in methanol (100 mL), acetic acid (50 mL) and dimethylformamide (50 mL), and mixed with palladium carbon (60 mg), and catalytic reduction was carried out under a hydrogen atmosphere at 80° C. for 1 hour and then at room temperature overnight. After completing the reaction, the catalyst was removed by filtration and the solvent was concentrated under reduced pressure. The residue was mixed with 5% aqueous sodium hydrogencarbonate to make it neutral and then extracted twice with chloroform. The organic layer thus obtained was dried over anhydrous sodium sulfate. Sodium sulfate was removed by filtration, and the solvent was distilled off under reduced pressure, and the residue thus obtained was purified by silica gel column chromatography (dichloromethane:methanol 15:1-10:1). The obtained product was purified by suspending in ethanol to obtain the title compound (OH-a01: white crystals, 489 mg, 59%). The analytical data of this compound were the same as that of the target compound obtained in Example 2-1A.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]([OH:22])[C@@H:9]2[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10]2)[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].Br[CH2:26][CH2:27][O:28][Si:29]([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30]>C1COCC1>[Si:29]([O:28][CH2:27][CH2:26][O:22][C@@H:8]([C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=1)[C@@H:9]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:19])([CH3:21])[CH3:20])=[O:16])[CH2:10]1)([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30]
Reactant: CC(C)(C)[Si](C)(C)OCCBr
Reactant: CC(C)(C)OC(=O)N1CCC[C@@H]([C@@H](O)c2cccc(Cl)c2)C1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCC[C@@H]([C@@H](OCCO[Si](C)(C)C(C)(C)C)c2cccc(Cl)c2)C1
Temperature: 80 °C

Procedure:
To a mixture of (R)-tert-butyl 3-((R)-(3-chlorophenyl)(hydroxy)methyl)piperidine-1-carboxylate (0.1964 g, 0.60 mmol, 1.0 equiv) and 60% NaH in oil (0.753 g, 18.8 mmol, 31 equiv) in THF (15 mL) was added (2-bromoethoxy)-tert-butyldimethylsilane (2.042 g, 8.5 mmol, 14 equiv). The resulting mixture was heated at 80° C. for 19 h and then quenched with water, extracted with EtOAc and dried over Na2SO4. After the solvent was removed, the crude product was used in the next step without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:24]=[CH:23][CH:22]=[CH:21][C:3]=1[O:4][C:5]1[CH2:9][N:8]([CH:10]([CH2:14][CH2:15][C:16]([F:19])([F:18])[F:17])[C:11](O)=[O:12])[C:7](=[O:20])[CH:6]=1.[CH3:25][C:26]1([CH3:38])[O:30][C@H:29]([CH2:31][N:32]2[CH:36]=[CH:35][C:34]([NH2:37])=[N:33]2)[CH2:28][O:27]1.C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C)C=O.C(OCC)(=O)C>[CH3:25][C:26]1([CH3:38])[O:30][C@H:29]([CH2:31][N:32]2[CH:36]=[CH:35][C:34]([NH:37][C:11](=[O:12])[CH:10]([N:8]3[CH2:9][C:5]([O:4][C:3]4[CH:21]=[CH:22][CH:23]=[CH:24][C:2]=4[Cl:1])=[CH:6][C:7]3=[O:20])[CH2:14][CH2:15][C:16]([F:19])([F:18])[F:17])=[N:33]2)[CH2:28][O:27]1
Reactant: O=C(O)C(CCC(F)(F)F)N1CC(Oc2ccccc2Cl)=CC1=O
Reactant: CC1(C)OC[C@@H](Cn2ccc(N)n2)O1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC1(C)OC[C@@H](Cn2ccc(NC(=O)C(CCC(F)(F)F)N3CC(Oc4ccccc4Cl)=CC3=O)n2)O1
Temperature: 25 °C
Reaction time: 8 h
Yield: 79.6 %

Procedure:
In a round bottom flask under argon was placed 2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-5,5,5-trifluoro-pentanoic acid (182 mg, 0.50 mmol) and 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-ylamine (prepared as in Example 49, 118 mg, 0.60 mmol) in N,N-dimethylformamide (4 mL). This mixture was treated with N,N-diisopropyethylamine (250 μL, 1.5 mmol) and (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (330 mg, 0.75 mmol) and stirred overnight at 25° C. After this time, the reaction was diluted with ethyl acetate (25 mL) and washed with a saturated aqueous solution of ammonium chloride (25 mL), saturated aqueous solution of sodium bicarbonate (25 mL) and a saturated aqueous solution of sodium chloride (25 mL), dried over sodium sulfate and concentrated with silica gel (2 g). Purification by Biotage flash chromatography (Aspire 40 g column, 80% ethyl acetate/hexanes) afforded 2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-5,5,5-trifluoro-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide (216 mg, 79%) as a white foam: HR-ES-MS m/z calculated for C24H26N4O5ClF3 [M+H]+ 543.1617, observed 543.1619.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8]Br)[C:3]=1[F:10].C[Si]([C:15]#[N:16])(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>CC#N>[Cl:1][C:2]1[C:3]([F:10])=[C:4]([CH2:8][C:15]#[N:16])[CH:5]=[CH:6][CH:7]=1
Reactant: Fc1c(Cl)cccc1CBr
Reactant: C[Si](C)(C)C#N
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: CC#N
Product: N#CCc1cccc(Cl)c1F
Temperature: 25 °C
Yield: 88 %

Procedure:
To a solution of 1-chloro-3-bromomethyl-2-fluoro-benzene (2.22 g, 10 mmol) in CH3CN (30 mL) was added trimethylsilyl cyanide (1.5 mL) and TBAF (1M in THF, 12 mmol, 12 mL). The resulting reaction mixture was heated at reflux temperature for 30 min. After cooling to room temperature, the volatiles were evaporated under reduced pressure. The residue was partitioned between EtOAc and water. The organic layer was then washed with brine, dried over anhy. Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash column chromatography to give the title compound (1.48 g, 88%). MS: 170.1 (M+H)+.
Reaction SMILES: CN1C2C(NC(=O)C3C=CC=CC=3)CCCC=2C2C1=C(F)C=C(F)C=2.[C:26]([NH:29][CH:30]1[CH2:42][C:41]2[C:40]3[C:35](=[C:36]([F:43])[CH:37]=[CH:38][CH:39]=3)[NH:34][C:33]=2[CH2:32][CH2:31]1)(=O)[CH3:27]>>[CH2:26]([NH:29][CH:30]1[CH2:42][C:41]2[C:40]3[C:35](=[C:36]([F:43])[CH:37]=[CH:38][CH:39]=3)[NH:34][C:33]=2[CH2:32][CH2:31]1)[CH3:27]
Reactant: CC(=O)NC1CCc2[nH]c3c(F)cccc3c2C1
Agent: Cn1c2c(c3cc(F)cc(F)c31)CCCC2NC(=O)c1ccccc1
Product: CCNC1CCc2[nH]c3c(F)cccc3c2C1

Procedure:
Following a reductive procedure similar to that described in Example 260 but substituting for 3-(N-methylbenzamido-6,8-difluoro-1,2,3,4-tetrahydrocarbazole an equivalent amount of 3-acetamido-8-fluoro-1,2,3,4-tetrahydrocarbazole there can be obtained 3-(ethylamino)-8-fluoro-1,2,3,4-tetrahydrocarbazole.
Reaction SMILES: [CH3:1][N:2]([CH3:23])[C:3]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[CH:6]=[CH:5][C:4]=1[C:12]1[NH:13][C:14]2[C:15]([N:22]=1)=[N:16][C:17]([O:20]C)=[CH:18][CH:19]=2.Cl>>[CH3:1][N:2]([CH3:23])[C:3]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[CH:6]=[CH:5][C:4]=1[C:12]1[N:22]=[C:15]2[NH:16][C:17](=[O:20])[CH2:18][CH:19]=[C:14]2[N:13]=1
Reactant: COc1ccc2[nH]c(-c3ccc([N+](=O)[O-])cc3N(C)C)nc2n1
Agent: Cl
Product: CN(C)c1cc([N+](=O)[O-])ccc1C1=NC2=CCC(=O)NC2=N1
Temperature: 0 °C

Procedure:
A quantity of 0.2 gm of 2-(2-dimethylamino-4-nitro-phenyl)-5-methoxy-imidazo[4,5-b]pyridine is heated in a bomb tube to 100° C. for three hours with 5 ml of concentrated hydrochloric acid. The reaction mixture is poured onto about 20 ml of ice, neutralized, and extracted with ethyl acetate. After washing with water and drying with magnesium sulfate, the ethyl acetate phase is evaporated. The residue is crystallized by trituration in ether/petroleum ether.
Reaction SMILES: C[N:2](C)/[CH:3]=[CH:4]/[C:5]([C:7]1[C:12](=[O:13])[CH:11]=[CH:10][N:9]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:21]([F:24])([F:23])[F:22])[CH:15]=2)[N:8]=1)=O.[F:26][C:27]1[CH:28]=[C:29]2[C:34](=[CH:35][CH:36]=1)[N:33]=[CH:32][CH:31]=[C:30]2[NH:37]N>>[F:26][C:27]1[CH:28]=[C:29]2[C:34](=[CH:35][CH:36]=1)[N:33]=[CH:32][CH:31]=[C:30]2[N:37]1[C:5]([C:7]2[C:12](=[O:13])[CH:11]=[CH:10][N:9]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:21]([F:24])([F:23])[F:22])[CH:15]=3)[N:8]=2)=[CH:4][CH:3]=[N:2]1
Reactant: CN(C)/C=C/C(=O)c1nn(-c2cccc(OC(F)(F)F)c2)ccc1=O
Reactant: NNc1ccnc2ccc(F)cc12
Product: O=c1ccn(-c2cccc(OC(F)(F)F)c2)nc1-c1ccnn1-c1ccnc2ccc(F)cc12

Procedure:
The product was obtained starting from 3-((E)-3-Dimethylamino-acryloyl)-1-(3-trifluoromethoxy-phenyl)-1H-pyridazin-4-one (A-6) and (6-fluoro-quinolin-4-yl)-hydrazine according to the method described for example 91. MS: M=468.2 (M+H)+
Reaction SMILES: [CH2:1]([C:3]1([CH2:18][CH3:19])[C:8]2[CH:9]=[C:10]([N+:13]([O-])=O)[CH:11]=[CH:12][C:7]=2[N:6]([CH3:16])[C:5](=[O:17])[O:4]1)[CH3:2].[BH4-].[Na+]>[Pd].CO>[NH2:13][C:10]1[CH:11]=[CH:12][C:7]2[N:6]([CH3:16])[C:5](=[O:17])[O:4][C:3]([CH2:18][CH3:19])([CH2:1][CH3:2])[C:8]=2[CH:9]=1
Reactant: CCC1(CC)OC(=O)N(C)c2ccc([N+](=O)[O-])cc21
Agent: [Pd]
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CCC1(CC)OC(=O)N(C)c2ccc(N)cc21
Temperature: 0 °C
Reaction time: 1 h
Yield: 80.5 %

Procedure:
To a stirred suspension of 4,4-diethyl-1-methyl-6-nitro-1,4-dihydro-2H-3,1-benzoxazin-2-one (3.74 g, 14.15 mmol) and 5% palladium on carbon (0.20 g) in methanol (35 mL) at 0° C. was added sodium borohydride (10.70 g, 28.30 mmol) portionwise. After stirring 1 hr at 0° C., the reaction was quenched with ice and ammonium chloride solution (sat.) and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine and dried over magnesium sulfate. Solvent was removed and trituration of the residue with ether gave 6-amino-4,4-diethyl-1-methyl-1,4-dihydro-2H-3,1-benzoxazin-2-one as a yellow solid (2.67 g, 81%). 1H NMR (DMSO-d6): δ 6.78 (d, J=8.6 Hz, 1H), 6.56 (m, 1H), 6.40 (d, J=2.4 Hz, 1H), 4.93 (s, 2H), 3.18 (s, 3H), 1.99 (m, 4H), 0.80 (t, J=7.3 Hz, 6H); MS (ESI) m/z 235 ([M+H]+); Anal. calcd for C13H18N2O2: C, 66.64; H7.74; N 11.96. Found: C, 64.97; H, 7.67; N, 11.62.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][N:5]1[C:10](=[O:11])[C:9]2[CH:12]=[CH:13][CH:14]=[CH:15][C:8]=2[Si:7]([CH3:17])([CH3:16])[CH2:6]1.C[Si]1(C)C2C([F:29])=CC=CC=2C(=O)NC1.C([Li])CCC.ClCCCBr>O1CCCC1>[Cl:1][CH2:2][CH2:3][CH2:4][N:5]1[C:10](=[O:11])[C:9]2[CH:12]=[CH:13][CH:14]=[C:15]([F:29])[C:8]=2[Si:7]([CH3:16])([CH3:17])[CH2:6]1
Reactant: C[Si]1(C)CNC(=O)c2cccc(F)c21
Reactant: C[Si]1(C)CN(CCCCl)C(=O)c2ccccc21
Agent: ClCCCBr
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: C[Si]1(C)CN(CCCCl)C(=O)c2cccc(F)c21

Procedure:
3-(3-Chloropropyl)-1,1-dimethyl-8-fluoro-4-oxo-1,2,3,4-tetrahydro-3,1-benzazasiline is obtained in a manner similar to that described in Example 4 for the preparation of 3-(3-chloropropyl)-1,1-dimethyl-4-oxo-1,2,3,4-tetrahydro-3,1-benzazasiline, but using 4.8 g of 1,1-dimethyl-8-fluoro-4-oxo-1,2,3,4-tetrahydro-3,1-benzazasiline, 17.2 cm3 of n-butyllithium, 8.7 g of 1-chloro-3-bromopropane and 70 cm3 of tetrahydrofuran. After purification by flash chromatography on a silica column under a nitrogen stream at moderate pressure (0.5-1.5 bar) with a dichloromethane-methanol mixture (98-2 by volume) as eluent, 2.75 g of 3-(3-chloropropyl)-1,1-dimethyl-8-fluoro-4-oxo- 1,2,3,4-tetrahydro-3,1-benzazasiline are obtained.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.[CH3:9][CH:10]([SH:12])[CH3:11].[H-].[Na+]>CN(C)C=O>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([S:12][CH:10]([CH3:11])[CH3:9])=[N:3][CH:4]=1
Reactant: Brc1ccc(Br)nc1
Reactant: CC(C)S
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)Sc1ccc(Br)cn1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a mixture of 2,5-dibromopyridine (2.07 g, 8.73 mmol) and 2-propanethiol (0.97 ml, 10.4 mmol) in N,N-dimethylformamide (20 ml) at 0° C. was added portionwise sodium hydride 60% dispersed in oil (450 mg, 11.3 mmol). The resulting mixture was stirred at room temperature for 1 hour, then partitioned between ether and water. The crude product from the organic phase was chromatographed on silica gel eluting with 10% ethyl acetate in hexane to afford the 5-Bromo-2-isopropylthiopyridine compound as a solid.
Reaction SMILES: [CH3:1][NH:2][C:3]1[C:8]([N+:9]([O-])=O)=[CH:7][N:6]=[C:5]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)=[CH:15][CH:14]=2)[N:4]=1>[Pd]>[NH2:9][C:8]1[C:3]([NH:2][CH3:1])=[N:4][C:5]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH2:20][CH2:21][O:22][CH2:23][CH2:24]3)=[CH:15][CH:14]=2)=[N:6][CH:7]=1
Reactant: CNc1nc(Nc2ccc(N3CCOCC3)cc2)ncc1[N+](=O)[O-]
Agent: [Pd]
Product: CNc1nc(Nc2ccc(N3CCOCC3)cc2)ncc1N

Procedure:
Hydrogenation of 4-(methylamino)-2-[(4-morpholinophenyl)amino]-5-nitropyrimidine (from Example 2(1) above) over palladium on charcoal (Pd/C) gave the title compound as a solid.
Reaction SMILES: CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[CH2:23]([O:30][CH2:31][CH2:32][CH2:33][C@H:34]([CH3:37])[CH2:35][OH:36])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C(Cl)Cl>[CH2:23]([O:30][CH2:31][CH2:32][CH2:33][C@H:34]([CH3:37])[CH:35]=[O:36])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: C[C@H](CO)CCCOCc1ccccc1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: ClCCl
Product: C[C@H](C=O)CCCOCc1ccccc1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 81.7 %

Procedure:
Dess-Martin periodinane (5.19 g, 12.23 mmol, 1.2 equiv) was added to a solution of 34 (2.1 g) in methylene chloride (20 ml) at 0° C. The mixture was stirred at room temperature for 10 min, filtered through a plug of celite and concentrated. Flash column chromatography (10% EtOAc/hexanes) gave aldehyde 25 (1.7 g, 82%) as a colorless oil: [α]22D=+15.5 (c=0.5, CHCl3); TLC Rf=0.87 (silica gel, 50% EtOAc/hexanes); 1H NMR (400 MHz, CDCl3) δ 9.6 (s, 1H), 7.37-7.26 (m, 5H), 4.5 (s, 2H), 3.51-3.46 (t, 3J=6 Hz, 2H), 2.41-2.32 (m, 1H), 1.87-1.78 (m, 1H), 1.74-1.60 (m, 2H), 1.52-1.42 (m, 1H), 1.115-1.097 (d, 3J=7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 205.23, 136.678, 128.62, 127.863, 73.187, 70.171, 46.298, 27.397, 13.529; HRMS calcd for C13H18O2+Na+ 229.1204; found 229.1221 [M+Na+].
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([CH2:19][O:20]C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[O:7][C@@H:6]1[O:40][CH2:41][C@H:42]([O:59][CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH2:72][CH3:73])[CH2:43][O:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH3:58])(=[O:3])[CH3:2]>C(O)(=O)C>[C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([CH2:19][OH:20])[O:7][C@@H:6]1[O:40][CH2:41][C@H:42]([O:59][CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH2:72][CH3:73])[CH2:43][O:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH3:58])(=[O:3])[CH3:2]
Reactant: CCCCCCCCCCCCCCOC[C@H](CO[C@H]1O[C@H](COC(c2ccccc2)(c2ccccc2)c2ccccc2)[C@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O)OCCCCCCCCCCCCCC
Solvent: CC(=O)O
Product: CCCCCCCCCCCCCCOC[C@H](CO[C@H]1O[C@H](CO)[C@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O)OCCCCCCCCCCCCCC
Temperature: 50 °C
Reaction time: 2 h
Yield: 55.9 %

Procedure:
3-O-(2,3,4-tri-O-acetyl-6-O-trityl-α-D-galactopyranosyl)-1,2-di-O-tetradecyl-Sn-glycerol (5) (599 mg) was mixed with 90% acetic acid (30 ml). The mixture was stirred at 50° C. for 2 hours and concentrated in vacuo. The residue was subjected to column chromatography (Wakogel C-300, 120 g) and eluted with 2.5% methanol-containing chloroform to obtain 3-O-(2,3,4-tri-O-acetyl-α-D-galactopyranosyl)-1,2-di-O-tetradecyl-Sn-glycerol (6) (255 mg, 60.8%).
Reaction SMILES: CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[OH:23][CH2:24][C@H:25]1[CH2:30][CH2:29][C@H:28]([C:31]([O:33][CH3:34])=[O:32])[CH2:27][CH2:26]1.S([O-])([O-])(=O)=S.[Na+].[Na+]>C1COCC1>[CH:24]([C@H:25]1[CH2:26][CH2:27][C@H:28]([C:31]([O:33][CH3:34])=[O:32])[CH2:29][CH2:30]1)=[O:23]
Reactant: COC(=O)[C@H]1CC[C@H](CO)CC1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: C1CCOC1
Product: COC(=O)[C@H]1CC[C@H](C=O)CC1

Procedure:
To a solution of Dess-Martin periodinane (542 mg, 1.28 mmol) in THF (2 mL) was added methyl trans-4-(hydroxymethyl)cyclohexanecarboxylate (200 mg, 1.18 mmol) at 0° C., and the reaction mixture was then stirred at 20° C. for 3 hours before the addition of saturated aqueous sodium thiosulfate solution (50 mL). The mixture was extracted with ethyl acetate and the combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by prep-TLC (ethyl acetate/petroleum ether) to give methyl trans-4-formylcyclohexanecarboxylate. MS ESI calc'd. for C9H15O3[M+H]+ 171. found 171. 1H NMR: (400 MHz, CDCl3) δ 9.63 (s, 1H), 3.68 (s, 3H), 2.36-2.17 (m, 2H), 2.13-2.04 (m, 4H), 1.55-1.45 (m, 2H), 1.37-1.25 (m, 2H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C@@:8]([NH:18][S@@:19]([C:21]([CH3:24])([CH3:23])[CH3:22])=[O:20])([CH2:11][C:12](=[O:17])[C:13]([F:16])([F:15])[F:14])[CH2:9][F:10])[CH:5]=[CH:6][CH:7]=1>CC(O)C>[Br:1][C:2]1[CH:3]=[C:4]([C@@:8]([NH:18][S@@:19]([C:21]([CH3:24])([CH3:23])[CH3:22])=[O:20])([CH2:11][C@H:12]([OH:17])[C:13]([F:15])([F:14])[F:16])[CH2:9][F:10])[CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)[S@@](=O)N[C@@](CF)(CC(=O)C(F)(F)F)c1cccc(Br)c1
Solvent: CC(C)O
Product: CC(C)(C)[S@@](=O)N[C@@](CF)(C[C@H](O)C(F)(F)F)c1cccc(Br)c1
Reaction time: 8 h
Yield: 85.1 %

Procedure:
Ru[p-cymeme](1S,2S)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine (0.119 g, 0.198 mmol) was added in one portion to a solution of (R)-N-((S)-2-(3-bromophenyl)-1,5,5,5-tetrafluoro-4-oxopentan-2-yl)-2-methylpropane-2-sulfinamide (2.14 g, 4.95 mmol) in IPA (50 ml) (which had been degassed by bubbling nitrogen through the solution for 30 minutes prior to use) in a dry box at room temperature. After stirring overnight, the reaction was worked up with saturated sodium bicarbonate solution and extracted with EtOAc three times. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated. The crude material was purified by column chromatography using 20-100% EtOAc/hexane to give (R)-N-((2S,4S)-2-(3-bromophenyl)-1,5,5,5-tetrafluoro-4-hydroxypentan-2-yl)-2-methylpropane-2-sulfinamide (1.83 g, 85% yield). MS m/z=435.8 [M+H]+. Calculated for C15H20BrF4NO2S: 434.3
Reaction SMILES: [O:1]1[C@H:3]([CH3:4])[CH2:2]1.[CH2:5]([Mg]Br)[CH2:6][CH2:7][CH:8]=[CH2:9].[NH4+].[Cl-]>C1COCC1>[CH3:4][C@@H:3]([OH:1])[CH2:2][CH2:9][CH2:8][CH2:7][CH:6]=[CH2:5]
Reactant: C=CCCC[Mg]Br
Reactant: C[C@@H]1CO1
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: C=CCCCC[C@@H](C)O
Temperature: 25 °C
Reaction time: 4 h
Yield: 63.4 %

Procedure:
(R)-(+)-1,2-epoxypropane (1.12 ml, 16.0 mmol) is dissolved in dry THF (23 ml) and CuBr (230 mg, 1.6 mmol) is added therein, after which the temperature is reduced −78° C. The 1M 4-pentenylmagnesium bromide solution (23 ml, 23.5 mmol) prepared in the reaction (1) is added to reaction mixture. The temperature is gradually increased to a room temperature and the mixture is stirred for 4 hours. The reaction is finished with saturated NH4Cl solution (10 ml). An obtained product is extracted with Et2O (20 ml×2) and it is washed by water (10 ml). An organic layer is dried using anhydrous MgSO4. The solution is vacuum concentrated, and then the compound (III) (1.3 g, 65%) is isolated using flash column chromatography (Et2O/n-pentene, 5:1, v/v):
Reaction SMILES: [F:1][C:2]1[C:3]([N:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)=[CH:4][C:5]2[N:14]=[CH:13][C:12]3[N:11]([CH3:15])[CH:10]=[C:9]([C:16]([O:18]CC)=[O:17])[C:8](=[O:21])[C:7]=3[C:6]=2[CH:22]=1.[OH-].[K+].Cl>C(O)C>[F:1][C:2]1[C:3]([N:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)=[CH:4][C:5]2[N:14]=[CH:13][C:12]3[N:11]([CH3:15])[CH:10]=[C:9]([C:16]([OH:18])=[O:17])[C:8](=[O:21])[C:7]=3[C:6]=2[CH:22]=1
Reactant: CCOC(=O)c1cn(C)c2cnc3cc(N4CCCC4)c(F)cc3c2c1=O
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: Cn1cc(C(=O)O)c(=O)c2c3cc(F)c(N4CCCC4)cc3ncc21
Temperature: 70 °C
Reaction time: 2 h
Yield: 87.9 %

Procedure:
A suspension of 0.8 g of ethyl 9-fluoro-4-methyl-1-oxo-8-pyrrolidinyl-1,4-dihydrobenzo[f][1,7]naphthyridine-2-carboxylate in a mixture of 60 Cm3 of aqueous ethanol at 50% and 2.8 cm3 of a 1 N aqueous potassium hydroxide solution was heated, with stirring, for 2 hours at a temperature of 70° C. After concentration under reduced pressure (5.2 kPa) at 60° C., the residue was dissolved in 100 cm3 of water; the light insoluble material was removed by filtration. The solution obtained was neutralized with 2.8 cm3 of a 1 N aqueous hydrochloric acid solution. The insoluble material formed was dewatered, washed 3 times with 20 cm of water, twice with 15 cm3 of ethanol and dried under vacuum at 100° C. 0.65 g of 9-fluoro-4-methyl-1-oxo-8-pyrrolidinyl-1,4-dihydrobenzo[f][1,7]naphthyridine-2-carboxylic acid was obtained in the form of yellow crystals, which melted at 365° C.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[NH:11][C:12](=[O:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[C:20](=O)([O-])[O-].[Cs+].[Cs+].CI>CN(C=O)C>[CH3:20][N:11]([C:3]1[CH:4]=[CH:5][C:6]([N+:8]([O-:10])=[O:9])=[CH:7][C:2]=1[CH3:1])[C:12](=[O:19])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: Cc1cc([N+](=O)[O-])ccc1NC(=O)c1ccccc1
Reactant: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CI
Solvent: CN(C)C=O
Product: Cc1cc([N+](=O)[O-])ccc1N(C)C(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 95 %

Procedure:
To a solution of N-(2-methyl-4-nitrophenyl)benzamide (Example 1099A) (0.38 g, 1.48 mmol) in DMF (2 mL) was added cesium carbonate (1.2 g, 3.68 mmol) followed by methyl iodide (0.12 mL, 1.9 mmol). The reaction mixture was stirred at room temp for 2 hr, extracted with EtOAc, washed with water and brine, dried and concentrated in vacuo to give N-methyl-N-(2-methyl-4-nitrophenyl)-benzamide (0.38 g, 95%). ES-MS (M+H)+=271.
Reaction SMILES: [OH:1][CH2:2][CH2:3][O:4][C:5]1[CH2:10][CH2:9]S[CH:7]2[S:11][C:12]([S:14]([NH2:17])(=[O:16])=[O:15])=[CH:13][C:6]=12.OO[S:20]([O-:22])=[O:21].[K+]>CO.O>[OH:1][CH2:2][CH2:3][O:4][C:5]1[CH2:10][CH2:9][S:20](=[O:22])(=[O:21])[CH:7]2[S:11][C:12]([S:14]([NH2:17])(=[O:16])=[O:15])=[CH:13][C:6]=12
Reactant: NS(=O)(=O)C1=CC2=C(OCCO)CCSC2S1
Reactant: O=S([O-])OO
Agent: [K+]
Solvent: CO
Solvent: O
Product: NS(=O)(=O)C1=CC2=C(OCCO)CCS(=O)(=O)C2S1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a stirred solution of 5,6-dihydro-4-(2-hydroxyethoxy)thieno[2,3-b]thiopyran-2-sulfonamide (1.0 g, 0.0034 mole) in CH3OH (20 ml) was added dropwise a solution of OXONE® (3.15 g, 0.005 mole) in water (20 ml). The mixture was stirred at ambient temperature overnight and then filtered, washing the filter cake thoroughly with CH3OH. Methanol was stripped from the filtrate in vacuo and the residue was extracted repeatedly with ethyl acetate. Evaporation of the dried extract left the crude product as a yellow gum that was purified by column chromatography on silica gel (75 g, 230-400 mesh). The product was eluted with 90 CHCl3 :10CH3OH:1H2O. Evaporation of the eluate left a colorless glass (0.8 g) that was triturated with ether, collected, dried in vacuo, and recrystallized from water. The yield of white crystalline product, m.p. 159°-164° C., was 430 mg (39%).