Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([N:7]2[CH2:15][C:14]3[C:13](=[O:16])[N:12]4[N:17]=[C:18]([C:20]5[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=5)[CH:19]=[C:11]4[NH:10][C:9]=3[C:8]2=[O:26])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].[CH2:33](Br)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.C(O)C>CN(C=O)C.O.C(Cl)(Cl)Cl.C(OC(=O)C)C>[CH:1]1([N:7]2[CH2:15][C:14]3[C:13](=[O:16])[N:12]4[N:17]=[C:18]([C:20]5[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=5)[CH:19]=[C:11]4[N:10]([CH2:33][C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)[C:9]=3[C:8]2=[O:26])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=C1c2[nH]c3cc(-c4ccccc4)nn3c(=O)c2CN1C1CCCCC1
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Solvent: CN(C)C=O
Solvent: ClC(Cl)Cl
Product: O=C1c2c(c(=O)n3nc(-c4ccccc4)cc3n2Cc2ccccc2)CN1C1CCCCC1
Temperature: 25 °C
Reaction time: 24 h
Yield: 84 %

Procedure:
To a suspension of 6-cyclohexyl-4,7-dihydro-2-phenyl-5H-pyrazolo[1,5-a]pyrrolo[3,4-d]pyrimidine-5,8(6H)-dione, prepared as described in Preparation 1 hereinabove, (2.00 g., 5.74 mmoles) and anhydrous potassium carbonate (795 mg., 5.75 mmole) in dry DMF (30 ml. in a flask there was added benzyl bromide (1.37 ml., 11.5 mmoles). The flask was stoppered tightly and stirred at room temperature for 24 hours. The mixture was diluted with water (150 ml.), stirred for 30 minutes and suction filtered. The collected solid was washed twice more water and air dried. The resulting solid was crystallized from an ethanol/chloroform, about 3/1 V/V ratio, 650 ml., dissolved at reflux temperature of the mixture and then cooled to 0° C. to afford 2.11 g. of the tilted product as fine, ivory colored needle crystals (84% yield,, m.p. 276°-278° C.). 1H NMR (CDCl3) 8.0 (m,2H, pyrazole o-phenyl), 7.3-7.5 (m,8H, phenyl), 6.44 (s, 1H, pyrazole-H), 5.93 (s, 2H, CH2 phenyl), 4.41 (s, 2H, lactam CH2), 4.18 (m, 1H, cyclohexyl CH), 1.1-2.0 (m, 10H, cyclohexyl CH2); IR (mull, cm1) 1697, 1679, 1618, 1591, 1577; UV (ethanol) λ max (ε)205(35,680), 227(23,860), 267(33,080), 285 sh (15,450), 295 sh (11,460) 338 (6,870); MS m/e (rel. intens.) 438(M+,15), 347(5), 91(100); Anal. calcd. for C27H26N4O2 : % Calcd.: C, 73.95; H, 5.98; N, 12.78; % Found: C, 73.88; H, 6.07; N, 12.80. TLC (silica, 4/1 V/V chloroform/ethylacetate) Rf 0.56.
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][CH:3]=1.[Cl:11][C:12]1[NH:20][C:19]2[C:18](=[O:21])[N:17]([CH2:22][CH2:23][CH2:24][CH2:25]/[C:26](=[N:29]/[H])/[NH:27]O)[C:16](=[O:31])[N:15]([CH2:32][CH2:33][CH3:34])[C:14]=2[N:13]=1.ClC1NC2C(=O)N(CCCC/C(=N/[H])/NO)C(=O)N(CCCCC)C=2N=1>CS(C)=O>[Cl:11][C:12]1[NH:20][C:19]2[C:18](=[O:21])[N:17]([CH2:22][CH2:23][CH2:24][CH2:25][C:26]3[N:27]=[C:6]([C:5]4[CH:4]=[CH:3][C:2]([OH:1])=[CH:10][CH:9]=4)[O:8][N:29]=3)[C:16](=[O:31])[N:15]([CH2:32][CH2:33][CH3:34])[C:14]=2[N:13]=1
Reactant: O=C(O)c1ccc(O)cc1
Reactant: [H]/N=C(/CCCCn1c(=O)c2[nH]c(Cl)nc2n(CCC)c1=O)NO
Agent: [H]/N=C(/CCCCn1c(=O)c2[nH]c(Cl)nc2n(CCCCC)c1=O)NO
Solvent: CS(C)=O
Product: CCCn1c(=O)n(CCCCc2noc(-c3ccc(O)cc3)n2)c(=O)c2[nH]c(Cl)nc21
Temperature: 90 °C
Reaction time: 2 h
Yield: 11 %

Procedure:
4-Hydroxybenzoic acid (18 mg, 0.13 mmol) and CDl (24 mg, 0.15 mmol) were stirred in anhydrous DMSO (0.9 ml) at rt for 1 h. (1Z)-5-(8-Chloro-2,6-dioxo-3-propyl-2,3,6,7-tetrahydro-1H-purin-1-yl)-N-hydroxypentanimidamide (50 mg, 0.15 mmol; prepared in a manner similar to (1Z)-5-(8-Chloro-2,6-dioxo-3-pentyl-2,3,6,7-tetrahydro-1H-purin-1-yl)-N-hydroxypentanimidamide as described in Example 128(b)) was added and the mixture was stirred at 90° C. for 2 h. The reaction mixture was purified by MDAP. The product fraction was combined and concentrated under high vacuum to give the title compound as a white solid (7 mg, 11%).
Reaction SMILES: [CH3:1][Si:2]([C:5]#[CH:6])([CH3:4])[CH3:3].Br[C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[CH2:15][C:16]([O:18][CH3:19])=[O:17].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCN(CC)CC>C1COCC1.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:14][C:12]1[CH:11]=[CH:10][C:9]([CH2:15][C:16]([O:18][CH3:19])=[O:17])=[C:8]([C:6]#[C:5][Si:2]([CH3:4])([CH3:3])[CH3:1])[CH:13]=1
Reactant: C#C[Si](C)(C)C
Reactant: COC(=O)Cc1ccc(F)cc1Br
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: COC(=O)Cc1ccc(F)cc1C#C[Si](C)(C)C
Temperature: 35 °C

Procedure:
A suspension of (trimethylsilyl)acetylene (0.696 g, 7.08 mmol), methyl 2-(2-bromo-4-fluorophenyl)acetate (A48) (0.500 g, 2.02 mmol), PPh3 (0.053 g, 0.202 mmol), CuI (39 mg, 0.202 mmol), Et3N (1.41 mL, 10.1 mmol) and PdCl2(PPh3)2 (0.142 g, 0.202 mmol) in THF (25 mL) was heated at 35° C. for 16 hours. The resulting mixture was adsorbed onto silica gel and purified using column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-40% EtOAc in petroleum benzine 40-60° C.) to yield the title compound A49 as a clear oil (0.212 g, 40%); LCMS-A: rt 6.830 min.
Reaction SMILES: [CH2:1]([C:3]1[C:4]([C:23]([C:25]2[NH:29][C:28]3[CH:30]=[CH:31][C:32]([C:34]#[N:35])=[CH:33][C:27]=3[N:26]=2)=[CH2:24])=[C:5]2[C:9](=[C:10]([CH3:12])[CH:11]=1)[N:8](S(C1C=CC(C)=CC=1)(=O)=O)[CH:7]=[CH:6]2)[CH3:2].[OH-].[K+]>CCO.C(Cl)Cl.FC(F)(F)CO>[CH2:1]([C:3]1[C:4]([C:23]([C:25]2[NH:29][C:28]3[CH:30]=[CH:31][C:32]([C:34]#[N:35])=[CH:33][C:27]=3[N:26]=2)=[CH2:24])=[C:5]2[C:9](=[C:10]([CH3:12])[CH:11]=1)[NH:8][CH:7]=[CH:6]2)[CH3:2]
Reactant: C=C(c1nc2cc(C#N)ccc2[nH]1)c1c(CC)cc(C)c2c1ccn2S(=O)(=O)c1ccc(C)cc1
Agent: [K+]
Agent: [OH-]
Solvent: ClCCl
Solvent: CCO
Solvent: OCC(F)(F)F
Product: C=C(c1nc2cc(C#N)ccc2[nH]1)c1c(CC)cc(C)c2[nH]ccc12
Temperature: 100 °C
Reaction time: 0.5 h

Procedure:
A mixture of 2-(1-(5-ethyl-7-methyl-1-tosyl-1H-indol-4-yl)vinyl)-1H-benzo[d]imidazole-5-carbonitrile (79 mg, 0.164 mmol) and KOH (46.1 mg, 0.822 mmol) in EtOH (3 mL) was stirred at 100° C. for 0.5 h under the microwave irradiation. The reaction mixture was diluted with CH2Cl2/2,2,2-trifluoroethanol (c.a. 9/1). The mixture was washed with H2O, dried over Na2SO4, and filtered and concentrated. The resulting residue was purified by RP-HPLC (HC-A), then (HC-B) to give the title compound. 1H NMR (400 MHz, DICHLOROMETHANE-d2 with about 5 μL TFA) δ ppm 8.46 (br. s., 1H), 8.04 (s, 1H), 7.86 (d, J=8.59 Hz, 1H), 7.73 (dd, J=1.14, 8.59 Hz, 1H), 7.37 (s, 1H), 7.27 (t, J=2.80 Hz, 1H), 7.07 (s, 1H), 6.25 (s, 2H), 2.47-2.65 (m, 5H), 1.14 (t, J=7.45 Hz, 3H). HRMS calcd. for C21H18N4 (M+H)+ 327.1610. found 327.1612.
Reaction SMILES: O.O.[Cl-].[Ca+2:4].[Cl-].[CH3:6][C:7]([C:10]1[CH:11]=[C:12]([C:21]2[S:25][C:24](=[S:26])[NH:23][N:22]=2)[CH:13]=[C:14]([C:17]([CH3:20])([CH3:19])[CH3:18])[C:15]=1[OH:16])([CH3:9])[CH3:8].C(O)C>O1CCCC1>[Ca:4].[CH3:9][C:7]([C:10]1[CH:11]=[C:12]([C:21]2[S:25][C:24](=[S:26])[NH:23][N:22]=2)[CH:13]=[C:14]([C:17]([CH3:18])([CH3:19])[CH3:20])[C:15]=1[OH:16])([CH3:6])[CH3:8]
Reactant: [Ca+2]
Agent: CC(C)(C)c1cc(-c2n[nH]c(=S)s2)cc(C(C)(C)C)c1O
Agent: [Cl-]
Solvent: C1CCOC1
Solvent: O
Solvent: CCO
Product: [Ca]
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Calcium chloride dihydrate (1.496, 0.0102 mole) is added in one portion to a solution of 5-[3,5-bis(1,1-dimethylethyl)-4-hydroxy-phenyl]-1,3,4-thiadiazole-2(3H)-thione (8.11 g, 0.0204 mole) in tetrahydrofuran (80 ml). The resulting mixture is stirred 2 hours at room temperature before absolute ethanol (80 ml) is added. The mixture is stirred overnight at room temperature. The solution is concentrated in vacuo and the residue dissolved in tetrahydrofuran and the product is precipitated by the addition of water. Filtration and drying at 80° C. in vacuo provides 4.7 g (6.8 g theor., 68%) 5-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]-1,3,4-thiadiazole-2-(3H)thione calcium (2:1) (salt), mp 212°-231° C., analyzed for 0.31 hydrate.
Reaction SMILES: COC(O[C@@H:6]1[C@@:26]2([CH3:27])[C:10](=[CH:11][CH:12]=[C:13]3[C@@H:25]2[CH2:24][CH2:23][C@@:22]2([CH3:28])[C@H:14]3[CH2:15][CH2:16][C@@H:17]2[CH:18]([CH:20]=[O:21])C)[CH2:9][C@@H:8](OC(OC)=O)[CH2:7]1)=O.[BH4-].[Na+].Cl>C(O)C.O>[CH2:20]([OH:21])[CH2:18][C@@H:17]1[C@:22]2([CH3:28])[C@H:14]([C:13]3[C@H:25]([CH2:24][CH2:23]2)[C@:26]2([CH3:27])[C:10]([CH2:9][CH2:8][CH2:7][CH2:6]2)=[CH:11][CH:12]=3)[CH2:15][CH2:16]1
Reactant: COC(=O)O[C@@H]1CC2=CC=C3[C@@H]4CC[C@H](C(C)C=O)[C@@]4(C)CC[C@@H]3[C@@]2(C)[C@@H](OC(=O)OC)C1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: C[C@]12CC[C@H]3C(=CC=C4CCCC[C@@]43C)[C@@H]1CC[C@@H]2CCO
Reaction time: 0.5 h

Procedure:
In 2 ml of ethanol was dissolved 100 mg of 1α,3β-bis(methoxycarbonyloxy)pregna-5,7-diene-20-carbaldehyde . Then, under ice-cooling, 20 mg of sodium borohydride was added and the reaction mixture was stirred for 30 minutes. The reaction mixture was neutralized with diluted hydrochloric acid under ice-cooling and, after diluted with water, extracted with diethyl ether. The extract was serially washed with aqueous sodium hydrogen carbonate solution and aqueous sodium chloride solution, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give 83 mg of 20-methyl-1α,3β-bis)methoxycarbonyloxy)pregna-5,7-dien-21-ol.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([C:12](=[O:14])[CH3:13])[C@@H:7]([CH3:15])[CH2:6][N:5]2S(C1C=CC(C)=CC=1)(=O)=O.S(=O)(=O)(O)O.[OH-].[Na+]>ClCCl>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([C:12](=[O:14])[CH3:13])[C@@H:7]([CH3:15])[CH2:6][NH:5]2
Reactant: CC(=O)N1c2ccc(Br)cc2N(S(=O)(=O)c2ccc(C)cc2)C[C@@H]1C
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Product: CC(=O)N1c2ccc(Br)cc2NC[C@@H]1C
Yield: 84.7 %

Procedure:
A 1-L round bottomed flask was charged with (S)-1-(6-bromo-2-methyl-4-tosyl-3,4-dihydroquinoxaline-1(2H)-yl)ethanone (13.32 g, 31.5 mmol) and sulfuric acid (67.1 mL, 1259 mmol). The reaction mixture was stirred until all the viscous oil had dissolved (ca. 1 h). The reaction mixture was then quenched over crushed ice (ca. 50 g). The mixture was carefully neutralized with 10 N sodium hydroxide (157 mL, 1573 mmol) while not allowing internal temperature to exceed 10° C. The mixture was diluted with dichloromethane (200 mL) and the layers separated. The aqueous layer was extracted with dichloromethane (100 mL). The organic layers were combined and concentrated under reduced pressure. The crude product was purified by column chromatography (eluting with 4:1 dichloromethane-ethyl acetate) to afford (S)-1-(6-bromo-2-methyl-3,4-dihydroquinoxaline-1(2H)-yl)ethanone (7.18 g, 85%) as an off-white solid. MS (ESI, pos. ion) m/z 269 [M+1]+.
Reaction SMILES: [CH3:1][C:2]1([C@H:8]2[C:42](=[O:43])[N:41]3[CH2:44][C@@H:38]([CH2:39][C@H:40]3[C:45]([O:47]C)=[O:46])[O:37][C:20]3=[N:21][C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][C:27]=4[C:28]([O:29][CH:30]4[CH2:35][CH2:34][N:33]([CH3:36])[CH2:32][CH2:31]4)=[C:19]3[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][C@@H:13]3[CH2:49][C@H:12]3[O:11][C:10](=[O:50])[NH:9]2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.O.[OH-].[Li+].CO.C(O)(=O)C>O.C1COCC1>[CH3:1][C:2]1([C@H:8]2[C:42](=[O:43])[N:41]3[CH2:44][C@@H:38]([CH2:39][C@H:40]3[C:45]([OH:47])=[O:46])[O:37][C:20]3=[N:21][C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][C:27]=4[C:28]([O:29][CH:30]4[CH2:35][CH2:34][N:33]([CH3:36])[CH2:32][CH2:31]4)=[C:19]3[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][C@@H:13]3[CH2:49][C@H:12]3[O:11][C:10](=[O:50])[NH:9]2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1
Reactant: COC(=O)[C@@H]1C[C@@H]2CN1C(=O)[C@H](C1(C)CCCCC1)NC(=O)O[C@@H]1C[C@H]1CCCCCc1c(nc3ccccc3c1OC1CCN(C)CC1)O2
Agent: [Li+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: CO
Solvent: C1CCOC1
Product: CN1CCC(Oc2c3c(nc4ccccc24)O[C@@H]2C[C@@H](C(=O)O)N(C2)C(=O)[C@H](C2(C)CCCCC2)NC(=O)O[C@@H]2C[C@H]2CCCCC3)CC1
Temperature: 25 °C

Procedure:
A round-bottom flask was charged with the product of step 6 (450 mg, 0.651 mmol) and lithium hydroxide monohydrate (137 mg, 3.26 mmol). MeOH (2171 μl), THF (2171 μl) and water (2171 μl) were successively added and the mixture was stirred at room temperature LCMS showed complete reaction after 2 hours. The reaction was quenched by addition of acetic acid (373 μl, 6.51 mmol). Water was added (20 mL) and the mixture was extracted with dichloromethane (2×20 mL) and ethyl acetate (20 mL). The combined organic extracts were dried over magnesium sulfate, filtered and concentrated in rotavap. Residual acetic acid was azeotropically removed with toluene to give the title compound as a crude product (450 mg, 0.665 mmol, 102% yield) as a white powder. No further purification was carried out.
Reaction SMILES: [N:1]1([C:7]2[N:12]=[CH:11][NH:10][C:9](=[O:13])[CH:8]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[Cl:14][C:15]1[C:22]([Cl:23])=[CH:21][CH:20]=[C:19]([Cl:24])[C:16]=1[CH:17]=O>>[Cl:14][C:15]1[C:22]([Cl:23])=[CH:21][CH:20]=[C:19]([Cl:24])[C:16]=1[CH2:17][N:4]1[CH2:5][CH2:6][N:1]([C:7]2[N:12]=[CH:11][NH:10][C:9](=[O:13])[CH:8]=2)[CH2:2][CH2:3]1
Reactant: O=c1cc(N2CCNCC2)nc[nH]1
Reactant: O=Cc1c(Cl)ccc(Cl)c1Cl
Product: O=c1cc(N2CCN(Cc3c(Cl)ccc(Cl)c3Cl)CC2)nc[nH]1

Procedure:
6-[4-(2,3,6-Trichloro-benzyl)-piperazin-1-yl]-3H-pyrimidin -4-one was prepared using Procedure A from 6-piperazin-1-yl-3H-pyrimidin-4-one (Intermediate 4) and 2,3,6-trichlorobenzaldehyde. Mass spectrum (ES) MH+=373.
Reaction SMILES: [OH:1][C:2]([CH3:8])([CH3:7])[CH2:3][C:4]([OH:6])=O.Cl.[NH2:10][C:11]1[N:12]=[C:13]2[CH:18]=[CH:17][C:16]([O:19][C:20]3[CH:21]=[CH:22][C:23]([CH3:36])=[C:24]([NH:26][C:27]([C:29]4[N:33]([CH3:34])[N:32]=[C:31]([CH3:35])[CH:30]=4)=[O:28])[CH:25]=3)=[N:15][N:14]2[CH:37]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[OH:1][C:2]([CH3:8])([CH3:7])[CH2:3][C:4]([NH:10][C:11]1[N:12]=[C:13]2[CH:18]=[CH:17][C:16]([O:19][C:20]3[CH:21]=[CH:22][C:23]([CH3:36])=[C:24]([NH:26][C:27]([C:29]4[N:33]([CH3:34])[N:32]=[C:31]([CH3:35])[CH:30]=4)=[O:28])[CH:25]=3)=[N:15][N:14]2[CH:37]=1)=[O:6]
Reactant: CC(C)(O)CC(=O)O
Reactant: Cc1cc(C(=O)Nc2cc(Oc3ccc4nc(N)cn4n3)ccc2C)n(C)n1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: Cc1cc(C(=O)Nc2cc(Oc3ccc4nc(NC(=O)CC(C)(C)O)cn4n3)ccc2C)n(C)n1
Yield: 65.4 %

Procedure:
In the same manner as in Example 278 and using 3-hydroxy-3-methylbutanoic acid (74 mg, 0.63 mmol), N-{5-[(2-aminoimidazo[1,2-b]pyridazin-6-yl)oxy]-2-methylphenyl}-1,3-dimethyl-1H-pyrazole-5-carboxamide hydrochloride (200 mg, 0.48 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (240 mg, 0.63 mmol), N,N-diisopropylethylamine (190 mg, 1.5 mmol) and N,N-dimethylformamide (7 mL) as starting materials, the title compound (150 mg, 66%) was obtained as a pale-yellow solid.
Reaction SMILES: [OH-].[Li+].[CH3:3][O:4][CH2:5][C:6]1[N:10]([CH3:11])[C:9]([C:12](=[O:18])[C:13]([O:15]CC)=[O:14])=[C:8]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:7]=1>CO>[CH3:3][O:4][CH2:5][C:6]1[N:10]([CH3:11])[C:9]([C:12](=[O:18])[C:13]([OH:15])=[O:14])=[C:8]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:7]=1
Reactant: CCOC(=O)C(=O)c1c(-c2ccccc2)cc(COC)n1C
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Product: COCc1cc(-c2ccccc2)c(C(=O)C(=O)O)n1C
Temperature: 25 °C
Reaction time: 3 h
Yield: 67.4 %

Procedure:
Lithium hydroxide (170 mg, 4.04 mmol) was added to a solution of ethyl 2-[5-(methoxymethyl)-1-methyl-3-phenyl-pyrrol-2-yl]-2-oxo-acetate (600 mg, 1.90 mmol) in methanol (20 mL) and stirred for 3 h at ambient temperature. The mixture was concentrated in vacuo and the residue dissolved in water and acidified with acetic acid. The mixture was extracted with ethyl acetate, the organic layer washed with brine, dried over anhydrous sodium sulphate and concentrated in vacuo to afford 2-[5-(methoxymethyl)-1-methyl-3-phenyl-pyrrol-2-yl]-2-oxo-acetic acid (350 mg, 64%) as a solid.
Reaction SMILES: Cl.[CH3:2][C:3]1[CH:12]=[C:11]([O:13]CC2C=CC(C3C(C(O)=O)=CC=CC=3)=CC=2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1.CS(C)=O.[N+](C1C=C(C=CC=1)CO)([O-])=O.CC1C=C(OCC2C=CC(C3C(C(OC)=O)=CC=CC=3)=CC=2)C2C(=CC=CC=2)N=1>>[CH3:2][C:3]1[CH2:12][C:11](=[O:13])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1
Reactant: Cc1cc(OCc2ccc(-c3ccccc3C(=O)O)cc2)c2ccccc2n1
Agent: COC(=O)c1ccccc1-c1ccc(COc2cc(C)nc3ccccc23)cc1
Agent: Cl
Agent: O=[N+]([O-])c1cccc(CO)c1
Solvent: CS(C)=O
Product: CC1=Nc2ccccc2C(=O)C1

Procedure:
(Example 2): 4'-[(2-Methylquinolin-4-yloxy)methyl]biphenyl-2-carboxylic acid hydrochloride, m.p. 184°-186° C.; NMR (d6 -DMSO): 2.93(s,3H), 5.67(s,2H), 7.38-7.72(m,8H), 7.77(dd,1H), 7.84(dd,1H), 8.08(dt,1H), 8.29(d,1H), 8.33(d,1H); mass spectrum (-ve FAB, DMSO/m-nitrobenzyl alcohol)(NBA): 368 (M-H)- ; microanalysis found: C,71.2; H,5.0; N,3.6; Cl, 8.6%, C24H19NO3.HCl requires:C,71.0; H,5.0; N,3.5; Cl,8.7%; starting from methyl 4'-[(2-methylquinolin-4-yloxy)methyl]biphenyl-2-carboxylate, obtained as a solid, m p 146° C.; NMR: 2.71(s,3H), 3.67(s,3H), 5.33(s,2H), 6.74(s,1H), 7.3-7.6(complex m,8H), 7.68(dt,1H), 7.87(dd,1H), 7.98(d,1H), 8.23(dd,1H); itself obtained from 2-methyl-4-quinolone, using analogous procedures to those described in Example 1;
Reaction SMILES: [CH:1]1([C:7]2[CH:12]=[CH:11][C:10]([NH:13][CH2:14][C@H:15]([OH:18])[CH2:16][OH:17])=[CH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:19](=O)(OCC)[O:20]CC.C[O-].[Na+]>C1(C)C=CC=CC=1>[CH:1]1([C:7]2[CH:8]=[CH:9][C:10]([N:13]3[CH2:14][C@@H:15]([CH2:16][OH:17])[O:18][C:19]3=[O:20])=[CH:11][CH:12]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: OC[C@@H](O)CNc1ccc(C2CCCCC2)cc1
Reactant: CCOC(=O)OCC
Agent: C[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: O=C1O[C@H](CO)CN1c1ccc(C2CCCCC2)cc1
Reaction time: 8 h
Yield: 87.6 %

Procedure:
A solution of 1.40 g (5.6 mmol) of (S)-3-(4-cyclohexyl-phenylamino)-propane-1,2-diol in 50 ml of toluene was treated with 0.73 g (6.2 mmol) of diethyl carbonate and 0.5 ml of a 1 molar sodium methylate solution and stirred overnight at an oil bath temperature of 110°. After distilling off the solvent the residue was treated with water and 5 ml of 1N hydrochloric acid and extracted with ethyl acetate. The organic phase was washed with sodium chloride solution, dried over magnesium sulfate and the solvent was distilled off. 1.35 g of (S)-3-(4-cyclohexylphenyl)-5-hydroxymethyl-oxazolidin-2-one were obtained in the form of colorless crystals from ethyl acetate/hexane. M.p.: 166°-168°. [α]D =+51.25° (c=0.8/CH3OH).
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[C:12](=[O:13])[C:11]2[CH:14]=[CH:15][S:16][C:10]=2[S:9](=[O:18])(=[O:17])[CH2:8][CH2:7]1.Cl.Cl.[N:21]1[CH:26]=[CH:25][CH:24]=[N:23][C:22]=1[N:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>O.C1(C)C=CC=CC=1.CN(C)C=O>[N:21]1[CH:26]=[CH:25][CH:24]=[N:23][C:22]=1[N:27]1[CH2:32][CH2:31][N:30]([CH2:2][CH2:3][CH2:4][CH2:5][N:6]2[C:12](=[O:13])[C:11]3[CH:14]=[CH:15][S:16][C:10]=3[S:9](=[O:18])(=[O:17])[CH2:8][CH2:7]2)[CH2:29][CH2:28]1
Reactant: c1cnc(N2CCNCC2)nc1
Reactant: O=C1c2ccsc2S(=O)(=O)CCN1CCCCCl
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [I-]
Solvent: O
Solvent: CN(C)C=O
Solvent: Cc1ccccc1
Product: O=C1c2ccsc2S(=O)(=O)CCN1CCCCN1CCN(c2ncccn2)CC1
Temperature: 90 °C
Reaction time: 3 h
Yield: 51.7 %

Procedure:
To a solution of 4.1 g of 4-(4-chlorobutyl)-2,3-dihydrothieno[3,2-f]-1,4-thiazepin-5(4H)-one 1,1-dioxide in 80 ml of a mixed solvent of N,N-dimethylformamide and toluene (1:1) were added 3.2 g of N-(2-pyrimidinyl)piperazine dihydrochloride, 3.8 g of potassium carbonate and 2.3 g of potassium iodide and the mixture was stirred for 3 hours at 90° C. Then, the mixture was poured into water and extracted with ethyl acetate. The extract was washed with water, dried over magnesium sulfate and the solvent was distilled off. The resulting residue was chromatographed on a silica gel and eluted using chloroform and methanol (95:5) as an eluent. The resulting crystals were recrystallized from ethanol to give 3.0 g of 2,3-dihydro-4-[4-(4-(2-pyrimidinyl)-1-piperazinyl)butyl]thieno[3,2-f]-1,4-thiazepin-5(4H)-one 1,1-dioxide as white crystals, melting at 161°-163° C.
Reaction SMILES: [C:1]1([CH2:7][C:8](=[O:10])[CH3:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>O>[C:1]1([CH2:7][C@@H:8]([OH:10])[CH3:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC(=O)Cc1ccccc1
Solvent: O
Product: C[C@H](O)Cc1ccccc1
Reaction time: 24 h

Procedure:
Washed phaseolus aureus L (green grams) 50 g. were taken into a conical flask and allowed to soak in deionised water (400 ml) for a period of 24 hr. Phenylacetone (0.500 g; 0.0037 moles) I(d) was added to the soaked phaseolus aureus L (green grams) in the above water, covered and allowed to shake for 24 hr at 15–20° C. Then the green grams were filtered off and washed with deionised water (3×100 ml). The combined filtrate was extracted with chloroform (3×500 ml). The chloroform layer was dried and the crude product obtained (330 mg). Pure 1-phenyl-(2S)-propan-2-ol II(d) was obtained after column chromatography with silica gel using chloroform as eluent.
Reaction SMILES: Cl.[CH2:2]([N:4]([CH2:9]/[CH:10]=[CH:11]/[C:12]#[C:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH2:5][C:6]([OH:8])=O)[CH3:3].ClC(OC)=O.C(N(CC)CC)C.[S:30]1[CH:34]=[CH:33][C:32]([C:35]2[CH:36]=[C:37](/[CH:41]=[CH:42]/[CH2:43][NH2:44])[CH:38]=[CH:39][CH:40]=2)=[CH:31]1>C(Cl)Cl>[S:30]1[CH:34]=[CH:33][C:32]([C:35]2[CH:36]=[C:37](/[CH:41]=[CH:42]/[CH2:43][NH:44][C:6](=[O:8])[CH2:5][N:4]([CH2:9]/[CH:10]=[CH:11]/[C:12]#[C:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH2:2][CH3:3])[CH:38]=[CH:39][CH:40]=2)=[CH:31]1
Reactant: NC/C=C/c1cccc(-c2ccsc2)c1
Reactant: CCN(C/C=C/C#CC(C)(C)C)CC(=O)O
Agent: COC(=O)Cl
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCN(C/C=C/C#CC(C)(C)C)CC(=O)NC/C=C/c1cccc(-c2ccsc2)c1
Reaction time: 0.5 h
Yield: 14.8 %

Procedure:
100 mg of (E)-N-ethyl-N-(6,6-dimethyl-2-hepten-4-ynyl)glycine hydrochloride was dissolved in 10 ml of methylene chloride, and 34 μl of methyl chloroformate and 0.1 ml of triethylamine were added under ice cooling. The mixture was stirred for 30 minutes, and a methylene chloride solution(5 ml) of 90 mg of (E)-3-[3-(3-thienyl)phenyl]-2-propenylamine was added, then the mixture was stirred at room temperature for 2 hours. The solvent was evaporated under reduced pressure, and ethyl acetate and water were added to the residue to extract it. The organic layer was separated, washed with a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate. The desiccant was separated by filtration and the solvent was evaporated under reduced pressure. The residue was purified by medium-pressure liquid chromatography [silica gel column, hexane→hexane/ethyl acetate=5/1] to give 24 mg (yield 17%) of the captioned compound as a pale yellow oil.
Reaction SMILES: [CH3:1][S:2]([N:5]1[CH2:10][CH2:9][CH:8]([OH:11])[CH2:7][CH2:6]1)(=[O:4])=[O:3].[H-].[Na+].F[C:15]1[CH:20]=[CH:19][C:18]([S:21]([N:24]([C:29]2[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=2)[CH2:25][CH:26]([CH3:28])[CH3:27])(=[O:23])=[O:22])=[CH:17][CH:16]=1>O>[F:35][C:32]1[CH:31]=[CH:30][C:29]([N:24]([CH2:25][CH:26]([CH3:28])[CH3:27])[S:21]([C:18]2[CH:19]=[CH:20][C:15]([O:11][CH:8]3[CH2:7][CH2:6][N:5]([S:2]([CH3:1])(=[O:4])=[O:3])[CH2:10][CH2:9]3)=[CH:16][CH:17]=2)(=[O:23])=[O:22])=[CH:34][CH:33]=1
Reactant: CS(=O)(=O)N1CCC(O)CC1
Reactant: CC(C)CN(c1ccc(F)cc1)S(=O)(=O)c1ccc(F)cc1
Agent: [H-]
Agent: [Na+]
Solvent: O
Product: CC(C)CN(c1ccc(F)cc1)S(=O)(=O)c1ccc(OC2CCN(S(C)(=O)=O)CC2)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 34.7 %

Procedure:
To a solution of 1-methanesulfonyl-piperidin-4-ol (61 mg) in anhydrous tetrohydrofuran (5 mL) at room temperature was added NaH (60% dispersion in mineral oil, 15 mg, 369 μmol) and the reaction was stirred at room temperature for 30 minutes. 4-Fluoro-N-(4-fluoro-phenyl)-N-isobutyl-benzenesulfonamide (100 mg, 308 μmol) was added and the reaction was heated at 90° C. for 3 hours. The reaction was allowed to cool to room temperature, water was added and then extracted with EtOAc, concentrated, purified by preparative reverse-phase HPLC and then freeze dried to give the title compound (51.8 mg). 1H NMR (400 MHz, DMSO): δ 7.44 (d, J=8.8 Hz, 2H), 7.13-7.14 (m, 7H), 4.69 (t, J=3.8 Hz, 1H), 3.35 (d, J=10.8 Hz, 4H), 3.28 (d, J=7.4 Hz, 3H), 3.12-3.14 (m, 2H), 2.91 (s, 3H), 2.03 (br s, 3H), 1.71-1.79 (m, 3H), 1.41 (t, J=6.8 Hz, 1H), 0.84 (d, J=6.6 Hz, 6H). LCMS (m/z, Method B) ES+ 484.9 [M+1]+.