Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:12]=[C:11]([OH:13])[CH:10]=[CH:9][C:3]=1[C:4]([CH2:6][C:7]#[N:8])=[O:5].[C:14]1(=O)[O:19][C:17](=[O:18])[CH2:16][CH2:15]1>N1C=CC=CC=1>[C:7]([C:6]1[C:4](=[O:5])[C:3]2[CH:9]=[CH:10][C:11]([OH:13])=[CH:12][C:2]=2[O:1][C:14]=1[CH2:15][CH2:16][C:17]([OH:19])=[O:18])#[N:8]
Reactant: O=C1CCC(=O)O1
Reactant: N#CCC(=O)c1ccc(O)cc1O
Solvent: c1ccncc1
Product: N#Cc1c(CCC(=O)O)oc2cc(O)ccc2c1=O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 8.85 g of 2,4-dihydroxybenzoyl acetonitrile, 25 ml of pyridine and 15 g of succinic anhydride was stirred at room temperature overnight. The next morning the solid was filtered and recrystallized from methanol, mp 300°-301° C.
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:35]=[CH:34][C:9]([CH2:10][N:11]2[CH2:16][CH2:15][N:14]([C:17]3[N:21]4[CH:22]=[CH:23][C:24](=[O:27])[CH:25]=[CH:26][C:20]4=[C:19]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[CH:18]=3)[CH2:13][CH2:12]2)=[CH:8][CH:7]=1)=[O:5])C.C(O)C.[OH-].[K+]>O>[C:4]([C:6]1[CH:7]=[CH:8][C:9]([CH2:10][N:11]2[CH2:16][CH2:15][N:14]([C:17]3[N:21]4[CH:22]=[CH:23][C:24](=[O:27])[CH:25]=[CH:26][C:20]4=[C:19]([C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)[CH:18]=3)[CH2:13][CH2:12]2)=[CH:34][CH:35]=1)([OH:5])=[O:3]
Reactant: CCOC(=O)c1ccc(CN2CCN(c3cc(-c4ccccc4)c4ccc(=O)ccn34)CC2)cc1
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: O=C(O)c1ccc(CN2CCN(c3cc(-c4ccccc4)c4ccc(=O)ccn34)CC2)cc1
Temperature: 60 °C
Yield: 53.2 %

Procedure:
To a stirred suspension of 3-[4-(4-ethoxycarbonylbenzyl)-1-piperazinyl]-1-phenyl-7H-pyrrolo[1,2-a]azepin-7-one (1.2 g), prepared as described in Example 20, and ethyl alcohol (30 cc) under an atmosphere of nitrogen, a solution of potassium hydroxide (0.2 g) in distilled water (3 cc) is added at a temperature of about 20° C. in the course of 5 minutes. The reaction mixture is then heated to 60° C. for 4 hours. After the solution is cooled, 1N aqueous potassium hydroxide solution (10 cc) is added and the mixture is washed 3 times with methylene chloride (150 cc in total). The organic phases are combined, dried over anhydrous magnesium sulphate, filtered and evaporated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C. The residue is dissolved in methylene chloride (5 cc) and the solution is poured into silica (40 g) contained in a column 1 cm in diameter. Elution is first performed with a mixture of cyclohexane and ethyl acetate (50:50 by volume) (2.5 liters) and the corresponding eluate is rejected. Elution is then performed with methanol (1 liter and the corresponding eluate is evaporated to dryness under reduced pressure (20 mm Hg; 1.7 kPa) at 40° C. After recrystallization in 2-methyl-2-butanol, 3-[4-(4-carboxybenzyl)-1-piperazinyl]-1-phenyl-7H-pyrrolo[1,2-a]azepin-7-one (0.6 g) is obtained in the form of its potassium salt.
Reaction SMILES: C(=O)(O)[O-].[Na+].[NH2:6][C@@H:7]([C:10]([OH:12])=[O:11])[CH2:8][OH:9].[CH2:13]([O:20][C:21](Cl)=[O:22])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>O>[CH2:13]([O:20][C:21]([NH:6][C@@H:7]([C:10]([OH:12])=[O:11])[CH2:8][OH:9])=[O:22])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: N[C@H](CO)C(=O)O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Product: O=C(N[C@H](CO)C(=O)O)OCc1ccccc1
Temperature: 2.5 °C
Reaction time: 10 h

Procedure:
Sodium bicarbonate (240 g) was added to a mixture of D-serine (100 g) and water (800 ml) at 0-5° C. Benzylchloroformate (50% solution in toluene)(480 ml) was added to the reaction mixture and stirred for 10 hours at 0-5° C. The organic and aqueous layers were separated and washed the aqueous layer with toluene. Aqueous layer pH was adjusted to 1.5 with hydrochloric acid and extract the reaction mixture in to ethyl acetate. Distilled off the solvent from the extracted reaction mixture under reduced pressure to get the title compound.
Reaction SMILES: C([O:8][C:9]1[C:10]([CH:16]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)O)=[N:11][C:12]([CH3:15])=[CH:13][CH:14]=1)C1C=CC=CC=1.C(OC(=O)C)(=O)C>N1C=CC=CC=1>[OH:8][C:9]1[C:10]([CH2:16][C:18]2[CH:19]=[CH:20][C:21]([O:24][CH3:25])=[CH:22][CH:23]=2)=[N:11][C:12]([CH3:15])=[CH:13][CH:14]=1
Reactant: COc1ccc(C(O)c2nc(C)ccc2OCc2ccccc2)cc1
Solvent: c1ccncc1
Solvent: CC(=O)OC(C)=O
Product: COc1ccc(Cc2nc(C)ccc2O)cc1
Reaction time: 4 h
Yield: 53.8 %

Procedure:
A mixture of 0.87 g of 3-benzyloxy-2-[(4-methoxyphenyl)hydroxymethyl]-6-methylpyridine, 2.5 ml of acetic acid anhydride and 20 ml of pyridine was heated under stirring for 4 hours in an oil bath kept at 120° C. After the reaction solution was evaporated, water was added thereto. The mixture was extracted with ethyl acetate, and the organic phase was washed with brine, dried over anhydrous magnesium sulfate and concentrated. To the residue were added 20 ml of methanol, 10 ml of tetrahydrofuran and a catalytic amount of 10% palladium/carbon, followed by stirring for 10 hours in a hydrogen atmosphere. After the catalyst was filtered off, the filtrate was concentrated. Then, the crystals were washed with diethyl ether, to give 320 mg of the target compound.
Reaction SMILES: [CH2:1]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH2:4][CH3:5].[C:18]([O:26][O:27][CH:28]([CH2:33][CH2:34][CH2:35][CH3:36])[CH:29](Br)[CH2:30][CH3:31])(=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[CH3:37][N:38](C)C=O.C(N)CN>O>[CH2:1]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH2:4][CH3:5].[C:18]([O:26][O:27][CH:28]([CH2:33][CH2:34][CH2:35][CH3:36])[CH:29]([C:37]#[N:38])[CH2:30][CH3:31])(=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: CN(C)C=O
Reactant: CCCCC(OOC(=O)c1ccccc1)C(Br)CC
Agent: CCCCCc1ccc(-c2ccccc2)cc1
Solvent: O
Solvent: NCCN
Product: CCCCC(OOC(=O)c1ccccc1)C(C#N)CC

Procedure:
2.75 g (5.10-3 moles) of p-pentyl biphenyl-3-bromo-4-octyloxy benzoate and 0.6 g (6.7.10-3 moles) of cuprous cyanide are introduced into 10 ml of dimethyl formamide. After system had been heated under reflux for 6 hours, it is cooled and poured into a mixture of 60 ml of deionized water and 5.5 ml of ethylene diamine. The solution is stirred and then extracted with ether. 2.3 g of crude product are obtained and then purified chromatographically on a column of silica, followed by recrystallization in ethanol. 1.8 g of pure product are obtained.
Reaction SMILES: [Br:1][C:2]1[CH:20]=[CH:19][C:5]([NH:6][CH2:7][C:8]2[CH:18]=[CH:17][C:11]3[N:12]=[C:13]([S:15][CH3:16])[S:14][C:10]=3[CH:9]=2)=[C:4]([N+:21]([O-])=O)[CH:3]=1.BrC1C(OC)=CC(NCC2C=CC3N=C(SC)SC=3C=2)=C([N+]([O-])=O)C=1>>[Br:1][C:2]1[CH:3]=[C:4]([NH2:21])[C:5]([NH:6][CH2:7][C:8]2[CH:18]=[CH:17][C:11]3[N:12]=[C:13]([S:15][CH3:16])[S:14][C:10]=3[CH:9]=2)=[CH:19][CH:20]=1
Reactant: CSc1nc2ccc(CNc3ccc(Br)cc3[N+](=O)[O-])cc2s1
Agent: COc1cc(NCc2ccc3nc(SC)sc3c2)c([N+](=O)[O-])cc1Br
Product: CSc1nc2ccc(CNc3ccc(Br)cc3N)cc2s1

Procedure:
4-Bromo-N1-((2-(methylthio)benzo[d]thiazol-6-yl)methyl)benzene-1,2-diamine was synthesized as a red oil using a procedure analogous to that described in Step 2 of Example 41, substituting 4-bromo-N-((2-(methylthio)benzo[d]thiazol-6-yl)methyl)-2-nitroaniline from the previous step for 4-bromo-5-methoxy-N-((2-(methylthio)benzo[d]thiazol-6-yl)methyl)-2-nitro aniline used in Example 41. LCMS (ESI) m/z 380, 382 (M+H)+.
Reaction SMILES: [CH:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][N:4]=1)=[O:2].[CH3:9][O:10][C:11]1[C:12]([CH2:17][CH2:18][CH2:19][CH2:20][NH:21][C:22]2[NH:23][CH:24]=[CH:25][C:26](=[O:28])[N:27]=2)=[N:13][CH:14]=[CH:15][CH:16]=1.Cl>>[CH3:9][O:10][C:11]1[C:12]([CH2:17][CH2:18][CH2:19][CH2:20][NH:21][C:22]2[NH:23][CH:24]=[C:25]([CH:1]([C:3]3[CH:8]=[CH:7][CH:6]=[CH:5][N:4]=3)[OH:2])[C:26](=[O:28])[N:27]=2)=[N:13][CH:14]=[CH:15][CH:16]=1
Reactant: COc1cccnc1CCCCNc1nc(=O)cc[nH]1
Reactant: O=Cc1ccccn1
Agent: Cl
Product: COc1cccnc1CCCCNc1nc(=O)c(C(O)c2ccccn2)c[nH]1

Procedure:
2-Formylpyridine is reacted with 2-(4-(3-methoxy-2-pyridyl)butylamino)-4(1H)-pyrimidinone in refluxing concentrated hydrochloric acid for 24 hours to give 2-(4-(3-methoxy-2-pyridyl)butylamino)-5-((2-pyridyl)hydroxymethyl)-4(1H)-pyrimidinone.
Reaction SMILES: [C:1]1([C:7]2[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([O:16][C:17]([C:19]1[S:20][CH:21]=[C:22]([CH2:24]Cl)[N:23]=1)=[O:18])C>>[C:7]1([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH:8]=[CH:9][C:10]([O:13][CH2:24][C:22]2[N:23]=[C:19]([C:17]([OH:18])=[O:16])[S:20][CH:21]=2)=[CH:11][CH:12]=1
Reactant: CCOC(=O)c1nc(CCl)cs1
Reactant: Oc1ccc(-c2ccccc2)cc1
Product: O=C(O)c1nc(COc2ccc(-c3ccccc3)cc2)cs1

Procedure:
4-(Biphenyl-4-yloxymethyl)-thiazole-2-carboxylic acid was prepared using general procedure B from 4-phenylphenol (available from Aldrich, Milwaukee, Wis.) and 4-chloromethyl-thiazole-2-carboxylic acid ethyl ester (Intermediate 4). Yield: 54 mg. Mass spectrum (ES) M-OH=294
Reaction SMILES: [CH3:1][C:2]([CH2:8][CH3:9])=[C:3]1[CH:7]=[CH:6][CH:5]=[CH:4]1.[CH3:10][Li].O>CCOCC>[CH3:1][C:2]([C:3]1[CH2:7][CH:6]=[CH:5][CH:4]=1)([CH3:10])[CH2:8][CH3:9]
Reactant: [Li]C
Reactant: CCC(C)=C1C=CC=C1
Solvent: CCOCC
Solvent: O
Product: CCC(C)(C)C1=CC=CC1
Temperature: 25 °C
Yield: 93 %

Procedure:
To a solution of 8.00 g (66.6 mmol) of 6-methyl-6-ethylfulvene in 40 ml of ether, 66.0 ml (75.2 mmol) of an ether solution of methyllithium was dropwise added in an nitrogen atmosphere with ice cooling, followed by stirring at room temperature for one night. Then, 30 ml of water was added. The separated organic phase was washed with water and a saturated saline solution, then dried over magnesium sulfate and filtered. From the filtrate, the solvent was removed under reduced pressure to obtain a liquid. The liquid was subjected to vacuum distillation (165° C./270 mmHg) to obtain 8.40 g (61.66 mmol) of a light yellow liquid (yield: 93%) The analyzed values are given below.
Reaction SMILES: [C:1]12([CH2:11][NH2:12])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[Cl:13][C:14]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:15]=1[C:16](O)=[O:17]>>[Cl:13][C:14]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:15]=1[C:16]([NH:12][CH2:11][C:1]12[CH2:8][CH:7]3[CH2:6][CH:5]([CH2:4][CH:3]([CH2:9]3)[CH2:2]1)[CH2:10]2)=[O:17]
Reactant: O=C(O)c1cc(F)ccc1Cl
Reactant: NCC12CC3CC(CC(C3)C1)C2
Product: O=C(NCC12CC3CC(CC(C3)C1)C2)c1cc(F)ccc1Cl

Procedure:
Prepared according to the method of Example 41 from 1-adamantanemethylamine (0.1 ml) and 2-chloro-5-fluorobenzoic acid (0.098 g) to give the title compound as a white solid (0.165 g).
Reaction SMILES: [CH2:1]=[CH:2][CH:3]1[CH2:8][CH:7]=[CH:6][CH2:5][CH2:4]1.[CH3:9][C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][C:19]=1[CH3:20])[C:16](=[O:21])[CH:15]=[CH:14][C:13]2=[O:22].C1C=CC=CC=1>[Pd].CO>[CH2:4]([CH:5]1[C:14]2[C:13](=[O:22])[C:12]3[C:17](=[CH:18][C:19]([CH3:20])=[C:10]([CH3:9])[CH:11]=3)[C:16](=[O:21])[C:15]=2[CH2:8][CH2:7][CH2:6]1)[CH2:3][CH2:2][CH3:1]
Reactant: C=CC1CC=CCC1
Reactant: Cc1cc2c(cc1C)C(=O)C=CC2=O
Agent: [Pd]
Solvent: CO
Solvent: c1ccccc1
Product: CCCCC1CCCC2=C1C(=O)c1cc(C)c(C)cc1C2=O
Reaction time: 4 h
Yield: 36 %

Procedure:
A 3.0 g. sample of the butadiene dimer-6,7-di-methylnaphthoquinone adduct was dissolved in 100 ml. benzene. After the addition of 0.30 g 10% Pd/C catalyst, the mixture was hydrogenated at 35 psi for four hours. After removal of catalyst by filtration, five drops DBN were added and the mixture was stirred overnight while exposed to air. The benzene was then blown off with air and the residue chromatographed on acidic alumina with a 9:1 benzene-ethyl acetate solution. The crude product (1.1 g.; 36% yield) was recrystallized from methanol to give an analytical sample with m.p. 88°-90° C.
Reaction SMILES: [CH3:1][S:2]([OH:5])(=[O:4])=[O:3].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH2:25]([O:32][CH2:33][C@H:34]1[N:38]([S:39]([C:42]2[CH:51]=[CH:50][C:49]3[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=3)[CH:43]=2)(=[O:41])=[O:40])[CH2:37][C@H:36](O)[CH2:35]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.N(C([O-])=O)=NC([O-])=O>C1(C)C=CC=CC=1.C(N(CC)CC)C>[CH2:25]([O:32][CH2:33][C@H:34]1[N:38]([S:39]([C:42]2[CH:51]=[CH:50][C:49]3[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=3)[CH:43]=2)(=[O:41])=[O:40])[CH2:37][C@@H:36]([O:3][S:2]([CH3:1])(=[O:5])=[O:4])[CH2:35]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: O=S(=O)(c1ccc2ccccc2c1)N1C[C@H](O)C[C@H]1COCc1ccccc1
Reactant: CS(=O)(=O)O
Agent: O=C([O-])N=NC(=O)[O-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: CS(=O)(=O)O[C@H]1C[C@@H](COCc2ccccc2)N(S(=O)(=O)c2ccc3ccccc3c2)C1
Reaction time: 0.08 h
Yield: 80.9 %

Procedure:
To a suspension of methanesulphonic acid (0.96 g) in toluene (30 ml) was added triethylamine (1.40 ml) and triphenylphosphine (2.72 g) at 0-5° C. The suspension was stirred for 5 minutes, and (3R,5S)-5-benzyloxymethyl-1-(naphthalene-2-sulfonyl)-pyrrolidin-3-ol (3.46 g) dissolved in toluene (20 ml) was added dropwise in 5 minutes, followed by diisipropyl azodicarboxylate (2.0 ml). The reaction mixture was stirred for 3 h at 85° C., poured onto ice/water and extracted with ethy acetate. The organic phase was washed with 10% KHSO4— and NaCl solutions, dried over magnesium sulphate and concentrated. The residue was chromatographed on silica gel using EtOAc/hexane 1:2 and 1:1 as eluents to obtain (3S,5S)-methanesulfonic acid 5-benzyloxymethyl-1-(naphthalene-2-sulfonyl)-pyrrolidin-3-yl ester (3.35 g) as a slightly yellow syrup, MS: 476 (MH+).
Reaction SMILES: C(N(CC)C(C)C)(C)C.[CH2:10]([O:12][P:13]([O:27][CH2:28][CH3:29])([O:15][C:16]1[CH:21]=[CH:20][C:19]([CH:22]=[CH:23][C:24]([OH:26])=O)=[CH:18][CH:17]=1)=[O:14])[CH3:11].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[NH2:54][CH2:55][C@@H:56]1[O:60][C:59](=[O:61])[N:58]([C:62]2[CH:67]=[CH:66][C:65]([C:68]3[S:69][CH2:70][C:71](=[O:74])[NH:72][N:73]=3)=[C:64]([F:75])[CH:63]=2)[CH2:57]1>CN(C=O)C>[F:75][C:64]1[CH:63]=[C:62]([N:58]2[CH2:57][CH:56]([CH2:55][NH:54][C:24]([CH:23]=[CH:22][C:19]3[CH:18]=[CH:17][C:16]([O:15][P:13](=[O:14])([O:12][CH2:10][CH3:11])[O:27][CH2:28][CH3:29])=[CH:21][CH:20]=3)=[O:26])[O:60][C:59]2=[O:61])[CH:67]=[CH:66][C:65]=1[C:68]1[S:69][CH2:70][C:71](=[O:74])[NH:72][N:73]=1
Reactant: CCOP(=O)(OCC)Oc1ccc(C=CC(=O)O)cc1
Reactant: NC[C@H]1CN(c2ccc(C3=NNC(=O)CS3)c(F)c2)C(=O)O1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCOP(=O)(OCC)Oc1ccc(C=CC(=O)NCC2CN(c3ccc(C4=NNC(=O)CS4)c(F)c3)C(=O)O2)cc1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 539.4 %

Procedure:
N,N-Diisopropylethylamine (0.507 ml, 2.91 mmol) was added to 3-[4-(diethoxy-phosphoryloxy)phenyl]acrylic acid (0.065 g, 0.217 mmol) [prepared according to the procedure described in Tetrahedron Lett 1996, 37, 3635] and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.124 g 0.326 mmol) in DMF (3 ml) and stirred for 20 minutes at room temperature. 2-[4-(5(S)-aminomethyl-2-oxo-oxazolidin-3-yl)-2-fluorophenyl]-4H-[1,3,4]thiadiazin-5-one (0.084 g, 0.259 mmol) was added and stirring continued at room temperature overnight. The reaction mixture was partially evaporated under vacuum, diluted with water (5 ml), and extracted with ethyl acetate (50 ml). The extract was washed with brine, dried (MgSO4), and evaporated. The residue was purified by PTLC (5% MeOH/DCM) to give pure product as a white solid (0.71 g, 54%); MS (m/z): [M+H]+=607.
Reaction SMILES: [NH2:1][C:2]1[O:6][C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:19](Cl)(=[O:35])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]>C(Cl)Cl>[C:19]([NH:1][C:2]1[O:6][C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:4][CH:3]=1)(=[O:35])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]
Reactant: CCCCCCCCCCCCCCCC(=O)Cl
Reactant: CCOC(=O)c1ccc(N)o1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCCCCCCCCCCCCCC(=O)Nc1ccc(C(=O)OCC)o1
Reaction time: 48 h

Procedure:
To a solution of 28.7 g. of ethyl 5-amino-2-furancarboxylate, 50 ml. of triethylamine and 300 ml. of methylene chloride is added 51.7 g. of palmitoyl chloride dropwise. The reaction mixture is allowed to stir for 48 hours. The solvent is evaporated and the residue dissolved in a small amount of methylene chloride. The methylene chloride solution is filtered through Magnesol and concentrated to an oil. The product is obtained by cryytallization of the residual oil from hexane.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][C:3]=1[CH2:10][OH:11].[C:12]1(=[O:21])[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:14][CH2:13]1.[OH-].[Na+].Cl>O.C(O)C>[OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[C:13]2[CH2:14][C:15]3[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:12]2=[O:21])=[CH:4][C:3]=1[CH2:10][OH:11]
Reactant: O=C1CCc2ccccc21
Reactant: O=Cc1ccc(O)c(CO)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: O=C1C(=Cc2ccc(O)c(CO)c2)Cc2ccccc21
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A mixture of 4-hydroxy-3-(hydroxymethyl)benzaldehyde (1.08 g), indan-1-one (0.94 g), ethanol (30 ml) and 5M aqueous sodium hydroxide solution (1.6 ml) was boiled under reflux for 6.5 hours. The mixture was cooled to ambient temperature and allowed to stand at that temperature for 16 hours. The mixture was diluted with water (45 ml) and then with 5M hydrochloric acid (1.6 ml) which was added with cooling. The precipitate formed was collected by filtration, washed with water and dried to give 2-(4-hydroxy-3-(hydroxymethyl)benzylidene)-1-indan-one, m.p. 194-195° C.
Reaction SMILES: O.[NH2:2][NH2:3].[C:4]([CH2:9][C:10]([O:12]CC)=O)(=O)[CH:5]([CH3:7])[CH3:6]>C(O)C>[CH:5]([C:4]1[CH2:9][C:10](=[O:12])[NH:2][N:3]=1)([CH3:7])[CH3:6]
Reactant: NN
Reactant: CCOC(=O)CC(=O)C(C)C
Solvent: O
Solvent: CCO
Product: CC(C)C1=NNC(=O)C1
Temperature: 22.5 °C
Yield: 66.5 %

Procedure:
70 g (1.26 mol) of hydrazine hydrate were added dropwise at 10 to 30° C. to a solution of 100 g (0.62 mol) of ethyl isobutyrylacetate in 60 ml of ethanol. After the exothermic reaction had subsided, the mixture was stirred at 20 to 25° C. for a further 14 hours approximately and was then cooled to approximately −10° C. 52 g of the title compound were isolated by filtration.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:16]=[CH:15][C:14]2[O:13][C:12]3[C:7]4=[C:8]([C:17](=[O:20])[NH:18][N:19]=[C:6]4[C:5]=2[CH:4]=1)[CH:9]=[CH:10][CH:11]=3.[P:21](Cl)([O:26][CH2:27][CH3:28])([O:23][CH2:24][CH3:25])=[O:22]>CN(C=O)C>[CH2:24]([O:23][P:21]([NH:1][CH2:2][C:3]1[CH:16]=[CH:15][C:14]2[O:13][C:12]3[C:7]4=[C:8]([C:17](=[O:20])[NH:18][N:19]=[C:6]4[C:5]=2[CH:4]=1)[CH:9]=[CH:10][CH:11]=3)(=[O:22])[O:26][CH2:27][CH3:28])[CH3:25]
Reactant: NCc1ccc2c(c1)-c1n[nH]c(=O)c3cccc(c13)O2
Reactant: CCOP(=O)(Cl)OCC
Solvent: CN(C)C=O
Product: CCOP(=O)(NCc1ccc2c(c1)-c1n[nH]c(=O)c3cccc(c13)O2)OCC
Yield: 50 %

Procedure:
To a solution of compound 49(0.5 mmol) in anhydrous DMF (20 mL) was added diethyl chlorophosphate (1.5 mmol). After 3 hours solution was concentrated in vacuo, and 50 mL of water was added. The aqueous layer was extracted with 30 mL of EtOAc twice. Organic layers were combined and washed with 30 mL of brine. Organic layer was dried with MgSO4. Solvent was removed to afford a white solid, which was recrystallized in 10% of EtOAc in hexanes to afford a white solid 54 in 50% yield. MS (ES−): 400; Mp: 222.3-224.5° C.; 1H-NMR (CDCl3, 400 MHz): 10.21 (s, 1H), 8.10 (d, J=2.5 Hz, 1H), 8.03 (d, J=7.5 Hz, 1H), 7.79 (t, J=8.0 Hz, 1H), 7.52 (d, J=8.0 Hz, 1H), 7.47 (dd, J=8.5 and 2.0 Hz, 1H), 7.22 (d, J=8.5 Hz, 1H), 4.12 (m, 6H), 1.32 (t, J=6.5 Hz, 6H); Anal. Calcd. for C19H20N3O5P·(0.3H2O): C, 56.10; H, 5.10; N, 10.33. Found: C, 56.00; H, 5.03; N, 10.13.
Reaction SMILES: [CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:24]([CH2:25][CH:26]([CH3:28])[CH3:27])[CH2:23][CH2:22][C:21]([C:29]([NH:31][C:32]4[CH:37]=[CH:36][C:35]([S:38][CH2:39][C:40]5[N:44]([CH2:45][CH2:46][CH3:47])[C:43]([S:48][CH3:49])=[N:42][N:41]=5)=[CH:34][CH:33]=4)=[O:30])=[CH:20][C:19]=3[CH:50]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4].ClC1C=CC=C(C(OO)=[O:59])C=1.S([O-])([O-])(=O)=S.[Na+].[Na+]>ClCCl>[CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:24]([CH2:25][CH:26]([CH3:27])[CH3:28])[CH2:23][CH2:22][C:21]([C:29]([NH:31][C:32]4[CH:33]=[CH:34][C:35]([S:38]([CH2:39][C:40]5[N:44]([CH2:45][CH2:46][CH3:47])[C:43]([S:48][CH3:49])=[N:42][N:41]=5)=[O:59])=[CH:36][CH:37]=4)=[O:30])=[CH:20][C:19]=3[CH:50]=2)=[CH:13][CH:14]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(SCc4nnc(SC)n4CCC)cc2)CCN3CC(C)C)cc1
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: ClCCl
Product: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(S(=O)Cc4nnc(SC)n4CCC)cc2)CCN3CC(C)C)cc1
Temperature: -78 °C
Reaction time: 1 h
Yield: 75.5 %

Procedure:
To a solution of 7-[4-(2-butoxyethoxy)phenyl]-1-isobutyl-N-[4-(5-methylthio-4-propyl-4H-1,2,4-triazol-3-ylmethylthio)phenyl]-2,3-dihydro-1H-benzazepine-4-carboxamide (0.80 g) in dichloromethane (10 ml) was added dropwise a solution of 3-chloroperbenzoic acid (70%, 0.41 g) in dichloromethane (10 ml) at −78° C., and the mixture was stirred for 1 hour at −78° C. To the reaction solution was added sodium thiosulfate solution at room temperature and the mixture was stirred for several minutes. The mixture was extracted with ethyl acetate, and the organic layer was washed with sodium bicarbonate solution and saturated brine, dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was separated and purified by column chromatography (basic silica gel, ethyl acetate), which was further recrystalized from ethyl acetate-hexane, to give 7-[4-(2-butoxyethoxy)phenyl]-1-isobutyl-N-[4-(5-methylthio-4-propyl-4H-1,2,4-triazol-3-ylmethylsulfinyl)phenyl]-2,3-dihydro-1H-benzazepine-4-carboxamide (Compound 149) (617.6 mg) as yellow crystals.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:13][CH2:12][NH:11][C:10](=[O:14])[C@H:9]2[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:4][CH:3]=1.[CH3:21][S:22](Cl)(=[O:24])=[O:23].O>N1C=CC=CC=1>[S:22]([O:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:13][CH2:12][NH:11][C:10](=[O:14])[C@H:9]2[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)=[CH:4][CH:3]=1)([CH3:21])(=[O:24])=[O:23]
Reactant: CS(=O)(=O)Cl
Reactant: O=C1NCC[C@@H](c2ccc(O)cc2)[C@@H]1c1ccccc1
Solvent: O
Solvent: c1ccncc1
Product: CS(=O)(=O)Oc1ccc([C@@H]2CCNC(=O)[C@H]2c2ccccc2)cc1
Reaction time: 1 h
Yield: 61 %

Procedure:
To a solution of 1.34 g (0.005 mol) of 27 in 10 cm3 of anhydrous pyridine, 1.14 g (0.01 mol; 0.77 cm3) of methanesulfonyl chloride are added under an atmosphere of nitrogen at 0° C. The mixture is stirred for 1 hour at between 0° and 3° C. before being poured into 70 cm3 of cold water. This mixture is extracted with methylene chloride and washed to neutrality. After evaporation and recrystallization in methanol, 29 is obtained in 61% yield. M.p. 199° C.