Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[NH:12][CH:11]([C:16]1[CH:17]=[C:18]([C:22]3[CH:27]=[CH:26][C:25]([C:28]([CH3:31])([CH3:30])[CH3:29])=[CH:24][CH:23]=3)[CH:19]=[CH:20][CH:21]=1)[CH2:10][C:9]2([CH3:33])[CH3:32])=[O:5])C.Cl>C(O)C.O1CCCC1.[OH-].[Na+].O>[C:28]([C:25]1[CH:24]=[CH:23][C:22]([C:18]2[CH:19]=[CH:20][CH:21]=[C:16]([CH:11]3[CH2:10][C:9]([CH3:33])([CH3:32])[C:8]4[C:13](=[CH:14][CH:15]=[C:6]([C:4]([OH:5])=[O:3])[CH:7]=4)[NH:12]3)[CH:17]=2)=[CH:27][CH:26]=1)([CH3:31])([CH3:29])[CH3:30]
Reactant: CCOC(=O)c1ccc2c(c1)C(C)(C)CC(c1cccc(-c3ccc(C(C)(C)C)cc3)c1)N2
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CCO
Product: CC(C)(C)c1ccc(-c2cccc(C3CC(C)(C)c4cc(C(=O)O)ccc4N3)c2)cc1
Temperature: 60 °C
Reaction time: 12 h
Yield: 189.5 %

Procedure:
A mixture of 2-(4′-tert-butyl-biphenyl-3-yl)-4,4-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid ethyl ester (0.17 g, 0.37 mmol) in ethanol (3 mL) and tetrahydrofuran (5 mL), 30% sodium hydroxide in water (1 mL). The reaction mixture was stirred at 60° C. for 12 h. The mixture was neutralized with a 3 N aqueous hydrochloric acid solution and extracted with ethyl acetate (2×50 mL), washed with water, dried over anhydrous sodium sulfate and then concentrated in vacuo to afford 2-(4′-tert-butyl-biphenyl-3-yl)-4,4-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid (0.29 g, 90%) as a white solid which was used for next step without further purification: MS (ESI) M+1=414.2.
Reaction SMILES: F[C:2]1[N:9]=[CH:8][CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[CH3:10][C:11]1[C:16]([OH:17])=[CH:15][CH:14]=[CH:13][N:12]=1>>[CH3:10][C:11]1[C:16]([O:17][C:2]2[N:9]=[CH:8][CH:7]=[CH:6][C:3]=2[C:4]#[N:5])=[CH:15][CH:14]=[CH:13][N:12]=1
Reactant: Cc1ncccc1O
Reactant: N#Cc1cccnc1F
Product: Cc1ncccc1Oc1ncccc1C#N

Procedure:
2-Fluoro-nicotinonitrile was reacted with 2-methyl-pyridin-3-ol according to the method of Example 85A to provide the title compound. MS (DCI/NH3) m/z 212 (M+1)+.
Reaction SMILES: [C:1]([O:7][CH3:8])(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].[C:9](Cl)(=O)CC>>[O:4]=[C:3]([CH2:5][CH3:9])[CH2:2][C:1]([O:7][CH3:8])=[O:6]
Reactant: COC(=O)CC(C)=O
Reactant: CCC(=O)Cl
Product: CCC(=O)CC(=O)OC
Yield: 45.5 %

Procedure:
According to the method described in Jikken Kaqaku Koza, Vol. 19, p. 441, 121 g of methyl 3-ketopentanoate was synthesized from 326 g of methyl acetoacetate and 189 g of propionyl chloride and then subjected to enantioselective hydrogenation using (+)-2,2'-bis[di(p-tolylphosphino)-1,1'-binaphthyl] tetrachlorodiruthenium-triethylamine [Ru2Cl4 (T-BINAP)2Et3N] according to the method disclosed in JP-A-63-310847, to obtain 110 g of methyl R-(-)-3-hydroxypentanoate. 100 g of this compound was treated in the same manner as in Step 1 of Example 1, to obtain 19 g of the desired compound having a boiling point of 60° to 65° C./1 mmHg and a chemical purity, as measured by GC, of 88.2%. The percent yield was 36.3%.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH2:13][C:14]([OH:16])=O)[NH:8][C:7]2=[O:17])([O-:3])=[O:2].[CH3:18][N:19](C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CN>CN(C=O)C>[CH3:18][NH:19][C:14](=[O:16])[CH2:13][N:9]1[C:10]2[C:6](=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:12][CH:11]=2)[C:7](=[O:17])[NH:8]1
Reactant: O=C(O)Cn1[nH]c(=O)c2cc([N+](=O)[O-])ccc21
Reactant: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: CN
Agent: F[B-](F)(F)F
Solvent: CN(C)C=O
Product: CNC(=O)Cn1[nH]c(=O)c2cc([N+](=O)[O-])ccc21
Reaction time: 8 h
Yield: 27.1 %

Procedure:
To a solution of crude (5-nitro-3-oxo-2,3-dihydro-indazol-1-yl)-acetic acid (0.14 g) in DMF, was added TBTU (0.20 g), followed by N,N-ethyldiisopropylamine (0.40 mL) and after 10 minutes methylamine (0.32 mL of a 2 M solution) was added. The reaction was stirred overnight and was quenched with 2N HCl (aq.) and extracted with EtOAc. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and evaporated. Flash column chromatography of the residue over silica gel afforded the desired N-methyl-2-(5-nitro-3-oxo-2,3-dihydro-indazol-1-yl)-acetamide (0.040 g) as a yellow solid. MS (ESI−):249.1 ([M−H]−).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][Cl:18])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:19][C:20]1[CH:28]=[C:27]([C:29]#[C:30][CH2:31][O:32][CH3:33])[C:23]2[O:24][CH2:25][O:26][C:22]=2[C:21]=1[NH2:34].C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>CN(C=O)C>[Cl:19][C:20]1[CH:28]=[C:27]([C:29]#[C:30][CH2:31][O:32][CH3:33])[C:23]2[O:24][CH2:25][O:26][C:22]=2[C:21]=1[NH:34][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][Cl:18])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1
Reactant: COCC#Cc1cc(Cl)c(N)c2c1OCO2
Reactant: COc1cc2c(Cl)ncnc2cc1OCCCCl
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Na+]
Solvent: CN(C)C=O
Product: COCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCCl)c(OC)cc23)c2c1OCO2
Yield: 66.6 %

Procedure:
This was prepared using the method described in example 4 using 4-chloro-7-(3-chloropropoxy)-6-methoxyquinazoline (400 mg, 1.39 mmol), 5-chloro-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-amine (367 mg, 1.53 mmol) and sodium bis(trimethylsilyl)amide (1.0M in THF, 2.90 ml) in DMF (3 ml). The crude product was purified by column chromatography on silica using ethyl acetate as eluent. There was thus obtained the title compound (454 mg, 66%) as a pale yellow solid; NMR Spectrum:(CDCl3) 2.39 (quintet, 2H), 3.46 (s, 3H), 3.79 (t, 2H), 3.98 (s, 3H), 4.33 (t, 2H), 4.35 (s, 2H), 6.07 (s, 2H), 6.94 (s, 1H), 7.07 (s, 1H), 7.10 (s, 1H), 7.29 (s, 1H), 8.63 (s, 1H); Mass Spectrum: M+H+ 490.
Reaction SMILES: S(Cl)([Cl:3])=O.O[CH2:6][CH:7]1[C:11]([CH3:18])([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[O:10][C:9](=[O:19])[NH:8]1>N1C=CC=CC=1>[Cl:3][CH2:6][CH:7]1[C:11]([CH3:18])([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[O:10][C:9](=[O:19])[NH:8]1
Reactant: O=S(Cl)Cl
Reactant: CC1(c2ccccc2)OC(=O)NC1CO
Solvent: c1ccncc1
Product: CC1(c2ccccc2)OC(=O)NC1CCl
Temperature: 25 °C
Reaction time: 1 h

Procedure:
1.5 ml (10 mMole) of thionyl chloride are slowly added dropwise at 0° to +5° C. to 1.04 g (5 mMole) of 4-hydroxymethyl-5-methyl-5-phenyl oxazolidin-2-one dissolved in 15 ml of pyridine. After 1 hour at 50° C., the reaction solution is stirred overnight at room temperature, poured onto ice and repeatedly extracted with chloroform. The combined chloroform phases dried over Na2SO4 are concentrated. The crystals formed are recrystallised from methanol.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:24])[CH:5]=[C:6]([C:13]1[CH:21]=[C:20]2[C:16]([CH:17]=[CH:18][NH:19]2)=[CH:15][C:14]=1[O:22][CH3:23])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH3:2].C(OC(=O)CC(C1C=CC=C2C=1C(C#N)=CN2)C1C=CC=CC=1)C>>[CH2:1]([O:3][C:4](=[O:24])[CH2:5][CH:6]([C:13]1[CH:21]=[C:20]2[C:16]([CH:17]=[CH:18][NH:19]2)=[CH:15][C:14]=1[O:22][CH3:23])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH3:2]
Reactant: CCOC(=O)C=C(c1ccccc1)c1cc2[nH]ccc2cc1OC
Agent: CCOC(=O)CC(c1ccccc1)c1cccc2[nH]cc(C#N)c12
Product: CCOC(=O)CC(c1ccccc1)c1cc2[nH]ccc2cc1OC

Procedure:
3-(5-Methoxy-1H-indol-6-yl)-3-phenyl-propionic acid ethyl ester CXXXIV was prepared from 3-(5-methoxy-1H-indol-6-yl)-3-phenyl-acrylic acid ethyl ester using the procedure described above for preparation of 3-(3-Cyano-1H-Indol-4-yl)-3-phenyl-propionic acid ethyl ester LIX (Example 14)
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH2:26][CH:27]2[CH2:30][C:29](C(O)=O)([C:31]([OH:33])=[O:32])[CH2:28]2)[CH:5]=[CH:6][C:7]=1[C:8]1[S:9][C:10]2[C:15]([N:16]=1)=[CH:14][CH:13]=[C:12]([C:17]1([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:19][CH2:18]1)[N:11]=2.CS(C)=O>O>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[C:8]1[S:9][C:10]2[C:15]([N:16]=1)=[CH:14][CH:13]=[C:12]([C:17]1([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH2:18][CH2:19]1)[N:11]=2)[CH2:26][C@@H:27]1[CH2:30][C@H:29]([C:31]([OH:33])=[O:32])[CH2:28]1
Reactant: O=C(O)C1(C(=O)O)CC(Cc2ccc(-c3nc4ccc(C5(c6ccccc6)CC5)nc4s3)c(F)c2)C1
Solvent: O
Solvent: CS(C)=O
Product: O=C(O)[C@H]1C[C@@H](Cc2ccc(-c3nc4ccc(C5(c6ccccc6)CC5)nc4s3)c(F)c2)C1
Temperature: 160 °C
Reaction time: 4 h

Procedure:
3-((3-Fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)-methyl)cyclobutane-1,1-dicarboxylic acid (0.360 g, 0.716 mmol) treated with 4 mL DMSO, fitted with a water cooled reflux condenser, and heated to 160° C. After 4 h, the reaction mixture was cooled to rt. The reaction mixture was partitioned between water and EtOAc. The organic layer was washed with water once, satd NaCl once and the organics were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to give a light yellow solid, as an approximately 2:1 mixture of isomers. Separation by SFC (Gradient with Chiralpak IC (21×250 mm, 5 micron), pure methanol with CO2 70 mL/min) gave (cis)-3-(3-fluoro-4-(5-(1-phenylcyclopropyl)-thiazolo[5,4-b]pyridine-2-yl)benzyl)cyclobutanecarboxylic acid as a white solid. MS (ESI) m/z: calculated: 458.2; Observed: 459.1 (M++1).
Reaction SMILES: CCN(C(C)C)C(C)C.[CH3:10][O:11][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]2[C:21]=1[O:20][C:19](=[O:22])[C:18]([C:23]([OH:25])=O)=[CH:17]2.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:50][N:51]1[C:55]([C:56]2[CH:57]=[C:58]([NH2:62])[CH:59]=[CH:60][CH:61]=2)=[CH:54][CH:53]=[N:52]1>CN(C=O)C>[CH3:50][N:51]1[C:55]([C:56]2[CH:57]=[C:58]([NH:62][C:23]([C:18]3[C:19](=[O:22])[O:20][C:21]4[C:16]([CH:17]=3)=[CH:15][CH:14]=[CH:13][C:12]=4[O:11][CH3:10])=[O:25])[CH:59]=[CH:60][CH:61]=2)=[CH:54][CH:53]=[N:52]1
Reactant: COc1cccc2cc(C(=O)O)c(=O)oc12
Reactant: Cn1nccc1-c1cccc(N)c1
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: COc1cccc2cc(C(=O)Nc3cccc(-c4ccnn4C)c3)c(=O)oc12
Temperature: 25 °C
Yield: 73.8 %

Procedure:
DIEA (0.012 mL, 0.071 mmol) was added to 8-methoxy-3-carboxy-coumarin (0.014 g, 0.065 mmol) and HATU (0.027 g, 0.071 mmol) in 0.5 mL of DMF with constant stirring at room temperature until a clear solution resulted. Subsequently, 3-(2-methyl-2H-pyrazol-3-yl)-phenylamine (0.011 g, 0.065 mmol) was added and allowed to react overnight when a solid precipitated out of solution. The resulting precipitate was filtered, dried under suction, and finally dried overnight in vacuo to give 0.018 g of product in 77% yield: LCMS (ESI) m/z 376 (MH+).
Reaction SMILES: Br[C:2]1[C:3]2[C:8]([CH:9]=[C:10]3[C:15]=1[CH:14]=[CH:13][CH:12]=[CH:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2.[C:16]1([BrH](O)(=O)=O)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(=O)([O-])[O-].[K+].[K+].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>CC([O-])=O.CC([O-])=O.[Pd+2].COCCOC>[C:16]1([C:2]2[C:3]3[C:8]([CH:9]=[C:10]4[C:15]=2[CH:14]=[CH:13][CH:12]=[CH:11]4)=[CH:7][CH:6]=[CH:5][CH:4]=3)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: Brc1c2ccccc2cc2ccccc12
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: COCCOC
Product: c1ccc(-c2c3ccccc3cc3ccccc23)cc1
Temperature: 80 °C
Reaction time: 9 h
Yield: 85 %

Procedure:
5.4 g (21.1 mmol) of 9-bromoanthracene, 2.6 g (21.1 mmol) of phenylbromic acid, 60 mg (0.21 mmol) of Pd(OAc)2, 10 ml (20 mmol) of a 2 mol/1 potassium carbonate (K2CO3) aqueous solution, 263 mg (0.84 mmol) of tri(orthotolyl)phosphine (P(o-tolyl)3), and 20 ml of 1,2-dimethoxyethane (abbrev.: DME) were mixed, and stirred for 9 hours at 80° C. After the reaction, the solid extracted was recovered by suction filtration. Then it was dissolved in toluene and filtered through Florisil, Celite, and alumina. After the filtrate was washed by water and a saturated saline solution, it was dried with magnesium sulfate. After natural filtration, the filtrate was concentrated, and the target substance of 9-phenylanthracene was obtained in a light brown solid form, weighing 21.5 g in a yield of 85% (synthesis scheme (j-3)).
Reaction SMILES: [BH4-].[Na+].[Br-].[CH3:4][O:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][CH:10]=[C:9]2[CH2:15][C:16]1[CH:17]=[N+:18]([CH2:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([N+:30]([O-:32])=[O:31])=[CH:26][CH:25]=2)[CH:19]=[CH:20][CH:21]=1>CO>[CH3:4][O:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][CH:10]=[C:9]2[CH2:15][C:16]1[CH2:17][N:18]([CH2:22][CH2:23][C:24]2[CH:25]=[CH:26][C:27]([N+:30]([O-:32])=[O:31])=[CH:28][CH:29]=2)[CH2:19][CH2:20][CH:21]=1
Reactant: COc1ccc2[nH]cc(Cc3ccc[n+](CCc4ccc([N+](=O)[O-])cc4)c3)c2c1
Agent: [BH4-]
Agent: [Br-]
Agent: [Na+]
Solvent: CO
Product: COc1ccc2[nH]cc(CC3=CCCN(CCc4ccc([N+](=O)[O-])cc4)C3)c2c1

Procedure:
Sodium borohydride in pellets (0.8 g; 0.0211 mol) was added to a cold (~0° C.) stirring mixture of compound of Description 7 [3-[(5-methoxy-1H-indol-3-yl)-methyl]-1-(2-(4-nitro-phenyl)-ethyl)-pyridinium bromide] (1.75 g; 0.0038 mol) in methanol (50 ml). The reaction mixture was stirred at 0° C. for 2 hours. The reaction was then quenched with a saturated solution of aqueous sodium carbonate and the solvent (methanol) was evaporated under vacuum. The product was extracted with methylene chloride. The organic extract was dried (MgSO4) and evaporated under vacuum giving the desired compound (1.38 g). The compound was used as such without further purification.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([Cl:8])[N:5]=[C:4]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[C:12]([F:17])[CH:11]=2)[N:3]=1.[CH:18]1([NH2:25])[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1.[OH-].[Na+].O>CC(C)=O>[Cl:8][C:6]1[N:7]=[C:2]([NH:25][CH:18]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[N:3]=[C:4]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[C:12]([F:17])[CH:11]=2)[N:5]=1
Reactant: Cc1ccc(Nc2nc(Cl)nc(Cl)n2)cc1F
Reactant: NC1CCCCCC1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC(C)=O
Product: Cc1ccc(Nc2nc(Cl)nc(NC3CCCCCC3)n2)cc1F

Procedure:
To 156a (1.0010 g, 3.7 mmol) dissolved in acetone (20 mL) was added a solution of N-cycloheptylamine (0.5 mL, 3.7 mmol) in acetone (5 mL) followed by addition of 2.5 N NaOH (1.5 mL, 3.7 mmol) and water (4 mL). The reaction mixture was allowed to stir at reflux for 3 hours under nitrogen. The reaction mixture was extracted 3 times with dichloromethane; the combined organic layers were washed with brine, and dried over potassium carbonate. After filtering, the sample was concentrated, and the resulting solid was dried overnight under vacuum. Flash column chromatography (SiO2, 70:30 hexanes:ethyl acetate) yielded a white solid (156b, 1.144 g, 88%), mp 149° C.; HPLC: Inertsil ODS-3V C18, 30:70 [KH2PO4 (0.01M, pH 3.2): CH3CN], 264 nm, Rt 28.9 min, 90.4% purity; MS (TOF MS ES+): m/z 427 (40.2), 351 (32.2), 350 (M+H, 100).
Reaction SMILES: C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.[CH3:34][O:35][C:36]1[C:41]([CH2:42][OH:43])=[CH:40][CH:39]=[CH:38][N:37]=1.[Br:44][C:45]1[CH:50]=[CH:49][C:48]([C:51]2[CH:56]=[CH:55][C:54](O)=[CH:53][CH:52]=2)=[CH:47][CH:46]=1>C1COCC1>[Br:44][C:45]1[CH:46]=[CH:47][C:48]([C:51]2[CH:56]=[CH:55][C:54]([O:43][CH2:42][C:41]3[C:36]([O:35][CH3:34])=[N:37][CH:38]=[CH:39][CH:40]=3)=[CH:53][CH:52]=2)=[CH:49][CH:50]=1
Reactant: COc1ncccc1CO
Reactant: Oc1ccc(-c2ccc(Br)cc2)cc1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COc1ncccc1COc1ccc(-c2ccc(Br)cc2)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a mixture of PPh3 (0.53 g, 2.03 mmol) and DIAD (0.4 mL, 2.03 mmol) in dry THF (3 mL) at 0° C. was added a mixture of (2-methoxy-pyridin-3-yl)-methanol (0.18 g, 1.27 mmol) from Step A and 4′-bromo-biphenyl-4-ol (0.33 g, 1.33 mmol) in dry THF (2 mL). After 1 hr, the reaction was warmed to room temperature and monitored by TLC. After the reaction was completed (˜4 h), the reaction mixture was concentrated under vacuo and then diluted with EtOAc. The precipitates were filtered. The filtrate was brought to the usual work-up. The resulting crude product was purified by chromatography (silica gel, 15% EtOAc/hexanes) to give the titled compound. MS: 370, 372 (M+H)+.
Reaction SMILES: [CH3:1][S:2]([C:4]1[CH:13]=[CH:12][C:11]2[NH:10][C:9]3=[CH:14][C:15]([C:17]([OH:19])=O)=[N:16][N:8]3[C:7](=[O:20])[C:6]=2[CH:5]=1)=[O:3].CN(C=O)C.C(N1C=CN=C1)(N1C=CN=C1)=O.O.[NH2:39][C:40]1[NH:44][N:43]=[N:42][N:41]=1>N1C=CC=CC=1>[CH3:1][S:2]([C:4]1[CH:13]=[CH:12][C:11]2[NH:10][C:9]3=[CH:14][C:15]([C:17]([NH:39][C:40]4[NH:44][N:43]=[N:42][N:41]=4)=[O:19])=[N:16][N:8]3[C:7](=[O:20])[C:6]=2[CH:5]=1)=[O:3]
Reactant: CS(=O)c1ccc2[nH]c3cc(C(=O)O)nn3c(=O)c2c1
Reactant: Nc1nnn[nH]1
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: CN(C)C=O
Solvent: O
Solvent: c1ccncc1
Product: CS(=O)c1ccc2[nH]c3cc(C(=O)Nc4nnn[nH]4)nn3c(=O)c2c1

Procedure:
From 4,9-dihydro-7-(methylsulfinyl)-9-oxo-pyrazolo-[5,1-b]quinazoline-2-carboxylic acid (1.40 g; 5 mmole), DMF (50 ml), 1,1'-carbonyl-diimidazole (2.43 g; is mmole) and 5-amino-1-H-tetrazole, monohydrate (0.62 g; 6 mmole), following the procedure of Example 3, there is obtained 4,9-dihydro-7-(methylsulfinyl)-9-oxo-N-1H-tetrazol-5-yl-pyrazolo[5,1-b]quinazoline-2-carboxamide with pyridine (4:3), mp>350°; after crystallization from pyridine-ether.
Reaction SMILES: C(O[C:4](=[O:14])[CH2:5][C:6](=O)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)C.[NH2:15][C:16]1[N:20]([CH3:21])[N:19]=[C:18]([CH3:22])[CH:17]=1>O>[CH3:21][N:20]1[C:16]2=[N:15][C:6]([C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=3)=[CH:5][C:4]([OH:14])=[C:17]2[C:18]([CH3:22])=[N:19]1
Reactant: CCOC(=O)CC(=O)c1ccccc1
Reactant: Cc1cc(N)n(C)n1
Solvent: O
Product: Cc1nn(C)c2nc(-c3ccccc3)cc(O)c12
Temperature: 120 °C
Reaction time: 8 h

Procedure:
96 gms. of benzoylacetic acid ethyl ester (0.5 mol.) are added dropwise to a stirred mixture of 55.5 gms. of 5-amino-1,3-dimethylpyrazole (0.5 mol) and 250 gms. of polyphosphorus acid heated to 120° C. After the reaction has occurred, which can be recognized by the changing of the color, the whole is heated for an additional hour at 120° C. After the mixture has cooled to room temperature, 600 ml. of water are added and stirring is continued until the compound becomes crystalline. The mixture is allowed to stand overnight and is then filtered off. The collected 1,3-dimethyl-4-hydroxy-6-phenyl-1H-pyrazolo[3,4-b]pyridine is washed with dilute ammonia, dried and treated with ethyl acetate yielding 73.6 gms. (61.6%), m.p. 262°-264°.
Reaction SMILES: [CH3:1][C:2]([NH:10][CH3:11])([CH3:9])[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].[CH2:12](Br)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH2:12]([N:10]([C:2]([CH3:1])([CH3:9])[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5])[CH3:11])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: BrCc1ccccc1
Reactant: CCOC(=O)CC(C)(C)NC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CCOC(=O)CC(C)(C)N(C)Cc1ccccc1

Procedure:
A mixture containing ethyl 3-methyl-3-methylaminobutanoate (95 g--see Preparation δ), benzyl bromide (72 ml), anhydrous potassium carbonate (138 g) and acetonitrile (500 ml) was heated under reflux for 1.5 hours. The mixture was concentrated in vacuo and the residue partitioned between dichloromethane (500 ml) and 10% aqueous potassium carbonate (300 ml). The layers were separated and the aqueous layer extracted with dichloromethane (2×100 ml). The combined dichloromethane extracts were dried (MgSO4) and concentrated in vacuo to give the title compound as a mobile, colourless oil, yield 150 g.
Reaction SMILES: [CH3:1][C:2]1([CH3:23])[N:6]=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[CH:4]([C:13]2[CH:22]=[CH:21][C:16]([N:17](C)[CH:18]=O)=[CH:15][CH:14]=2)[O:3]1>C(O)C>[CH3:18][NH:17][C:16]1[CH:15]=[CH:14][C:13]([CH:4]2[O:3][C:2]([CH3:23])([CH3:1])[N:6]=[C:5]2[C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[CH:22][CH:21]=1
Reactant: CN(C=O)c1ccc(C2OC(C)(C)N=C2c2ccccc2)cc1
Solvent: CCO
Product: CNc1ccc(C2OC(C)(C)N=C2c2ccccc2)cc1
Yield: 55 %

Procedure:
5 g of 4'-(2,2-dimethyl-4-phenyl-3-oxazoline-5-yl)-N-methylformanilide were exposed to light in 2 liters of ethanol under an atmosphere of argon for 8 hours in the apparatus described in Example 4. After evaporation of the solvent in a water-jet vacuum, there remained behind an oil which was chromatographed on silica gel. The elution was carried out with dichloromethane/acetone (95:5). In order to remove accompanying impurities, the product isolated in the foregoing manner was suspended in hot petroleum ether (boiling range 80°-110° C.), removed by filtration under suction and washed on the suction filter with petroleum ether. After drying at 60° C. in a water-jet vacuum, there were obtained 2.5 g of 5-[p-(methylamino)phenyl]-2,2-dimethyl-4-phenyl-3-oxazoline having a melting point of 138°-139° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10](Cl)=[O:11])=[CH:5][CH:4]=1.C(N(CC)CC)C.[C:20]1([SH:26])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.CCCC(C)C.C(OCC)(=O)C>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10](=[O:11])[S:26][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:5][CH:4]=1
Reactant: COc1ccc(CC(=O)Cl)cc1
Reactant: Sc1ccccc1
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: COc1ccc(CC(=O)Sc2ccccc2)cc1
Yield: 96.6 %

Procedure:
2-(4-Methoxyphenyl)acetyl chloride (3.06 mL, 20.0 mmol) in 60 mL toluene was added to a solution of triethylamine (2.80 mL, 20.1 mmol) and thiophenol (2.04 mL, 20.0 mmol) in 40 mL toluene. Reaction monitoring was accomplished by TLC: iso-hexane/ethyl acetate 25:1, Rf=0.29. Workup yielded 4.99 g (97%) S-phenyl 2-(4-methoxyphenyl)ethanethioate 3 as crystalline yellow solid.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.[H-].[Na+].[CH:13]([Si:16](Cl)([CH:20]([CH3:22])[CH3:21])[CH:17]([CH3:19])[CH3:18])([CH3:15])[CH3:14]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([Si:16]([CH:20]([CH3:22])[CH3:21])([CH:17]([CH3:19])[CH3:18])[CH:13]([CH3:15])[CH3:14])[CH:6]=[CH:5]2
Reactant: CC(C)[Si](Cl)(C(C)C)C(C)C
Reactant: Brc1ccc2[nH]ccc2c1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C)[Si](C(C)C)(C(C)C)n1ccc2cc(Br)ccc21
Temperature: 0 °C
Reaction time: 1 h
Yield: 75.5 %

Procedure:
5-Bromoindole (1.4 gm, 7.14 mmol) was dissolved in dry THF (50 ml) and cooled to 0° C., which was followed by the addition of NaH (0.34 g, 14.28 mmol) portion wise. The reaction mixture was allowed to stir at room temperature for 1 h. The reaction mixture was again cooled to 0° C. and triisopropylsilyl chloride (1.78 g, 9.28 mmol) was added drop wise. The mixture was allowed to warm to room temperature and was stirred overnight. The solvent was evaporated under reduced pressure and triturated with ethyl acetate (100 ml). The organic layer was washed with brine (50 ml) and dried over Na2SO4 and evaporated. The compound was purified by flash column chromatography using pure hexanes to afford colorless oily product 47 (1.90 g, 76%). 1H NMR (400 MHz, CDCl3) δ 1.13 (d, 18H, J=8.0 Hz), 1.63-1.71 (m, 3H), 6.56 (d, 1H, J=3.2 Hz), 7.20-7.25 (m, 2H), 7.37 (d, 1H, J=8.8 Hz), 7.74 (d, 1H, J=2.0 Hz).
Reaction SMILES: [CH3:1][C:2](=O)[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11].C(OP([CH2:21][C:22]([O:24][CH3:25])=[O:23])(OCC)=O)C.C[O-].[Na+]>C1C=CC=CC=1.CO>[CH3:11][C:10]([CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][CH3:1])=[CH:21][C:22]([O:24][CH3:25])=[O:23]
Reactant: CCCCCCCCCC(C)=O
Reactant: CCOP(=O)(CC(=O)OC)OCC
Agent: C[O-]
Agent: [Na+]
Solvent: c1ccccc1
Solvent: CO
Product: CCCCCCCCCC(C)=CC(=O)OC
Temperature: 25 °C
Reaction time: 8 h

Procedure:
2-Undecanone (methyl nonyl ketone) (1′) (73.9 g, 434 mmols) and methyl (diethylphosphono)acetate (99.4 g, 433 mmols) were dissolved in dry benzene (300 ml). The solution was stirred at room temperature, and a 28% sodium methoxide solution (83.7 g) in methanol was slowly added. Stirring was continued overnight at room temperature. The reaction mixture was poured into ice water, and extracted with diethyl ether. The organic layer was washed (water and a saturated aqueous solution of sodium chloride), and dried (sodium sulfate), followed by removing the solvent in a vacuum to obtain methyl 3-methyl-2-dodecenoate (2′) as a geometric isomer mixture.