Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4]([NH:19][CH:20]([CH2:22][CH2:23][CH2:24][O:25][C:26]2[CH:31]=[C:30]([N+:32]([O-])=O)[CH:29]=[CH:28][C:27]=2[N:35]2[CH:39]=[N:38][C:37]([CH3:40])=[N:36]2)[CH3:21])[C:5]2[CH2:10][CH2:9][CH:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=3[F:18])[C:6]=2[N:7]=1.CO.C1COCC1.[Cl-].[NH4+]>[Fe].O>[NH2:32][C:30]1[CH:29]=[CH:28][C:27]([N:35]2[CH:39]=[N:38][C:37]([CH3:40])=[N:36]2)=[C:26]([CH:31]=1)[O:25][CH2:24][CH2:23][CH2:22][CH:20]([NH:19][C:4]1[C:5]2[CH2:10][CH2:9][CH:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=3[F:18])[C:6]=2[N:7]=[C:2]([Cl:1])[N:3]=1)[CH3:21]
Reactant: Cc1ncn(-c2ccc([N+](=O)[O-])cc2OCCCC(C)Nc2nc(Cl)nc3c2CCC3c2ccc(F)cc2F)n1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CO
Solvent: C1CCOC1
Solvent: O
Product: Cc1ncn(-c2ccc(N)cc2OCCCC(C)Nc2nc(Cl)nc3c2CCC3c2ccc(F)cc2F)n1
Temperature: 70 °C
Reaction time: 2 h
Yield: 81.2 %

Procedure:
Iron powder-325 mesh (0.63 g, 11.4 mmol) was added to a round bottom flask charged with a mixture of 2-chloro-7-(2,4-difluorophenyl)-N-(5-(2-(3-methyl-1H-1,2,4-triazol-1-yl)-5-nitrophenoxy)pentan-2-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine (0.65 g, 1.14 mmol), methanol (15 mL), THF (30 mL), water (15 mL) and ammonium chloride (0.61 g, 11.4 mmol). A water-cooled reflux condenser was attached to the flask and the heterogeneous mixture was heated at 70° C. with vigorous stirring for 2 h. The reaction mixture was filtered and washed with methanol. The filtrate was concentrated in vacuo. EtOAc (250 mL) was added to the residue and was washed with brine. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to afford the light yellow solid N-(5-(5-amino-2-(3-methyl-1H-1,2,4-triazol-1-yl)phenoxy)pentan-2-yl)-2-chloro-7-(2,4-difluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine (500 mg, 81%). LC-MS (M+H)+=540.2. 1H NMR (400 MHz, CDCl3) δ ppm 8.32 (1H, s), 7.32-7.30 (1H, m), 6.96-6.94 (1H, m), 6.81-6.75 (2H, m), 6.34-6.29 (2H, m), 4.83 (1H, br m), 4.44-4.43 (2H, m), 4.09-4.00 (2H, m), 3.77 (2H, br s), 3.13-3.12 (1H, m), 2.64-2.56 (2H, m), 2.47 (3H, s), 1.94-1.80 (3H, m), 1.63-1.61 (2H, m), 1.27-1.22 (3H, m).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12](Br)=[CH:11][C:10]=1[F:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.[CH:23]([Si:26]([CH:41]([CH3:43])[CH3:42])([CH:38]([CH3:40])[CH3:39])[N:27]1[C:31]2=[N:32][CH:33]=[CH:34][CH:35]=[C:30]2[C:29]([CH:36]=[O:37])=[CH:28]1)([CH3:25])[CH3:24].O>O1CCCC1.CCOCC>[CH2:1]([O:8][C:9]1[C:10]([F:17])=[CH:11][C:12]([C:28]2[N:27]([Si:26]([CH:41]([CH3:43])[CH3:42])([CH:38]([CH3:39])[CH3:40])[CH:23]([CH3:25])[CH3:24])[C:31]3=[N:32][CH:33]=[CH:34][CH:35]=[C:30]3[C:29]=2[CH2:36][OH:37])=[C:13]([F:15])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Fc1cc(OCc2ccccc2)c(F)cc1Br
Reactant: CC(C)[Si](C(C)C)(C(C)C)n1cc(C=O)c2cccnc21
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: C1CCOC1
Solvent: O
Product: CC(C)[Si](C(C)C)(C(C)C)n1c(-c2cc(F)c(OCc3ccccc3)cc2F)c(CO)c2cccnc21
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
To 1-Benzyloxy-4-bromo-2,5-difluoro-benzene (47, 0.84 g, 2.80 mmol) in tetrahydrofuran (15.0 mL) and ether (15.0 mL), under an atmosphere of nitrogen at −78° C., n-butyllithium (1.20 mL, 2.50 M in hexane) was added slowly. After 20 minutes, 1-Triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde (8, 0.82 g, 0.0027 mol, prepared as described in Example 5) was added to the reaction. After 20 minutes, the reaction was allowed to warm to room temperature for 10 minutes, then poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified with silica gel column chromatography eluting with 20% ethyl acetate in hexane to a white solid (48, 10 g, 70.0%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([CH2:18][C:19]3[N:24]=[C:23]([C:25](=[N:27][OH:28])[NH2:26])[CH:22]=[CH:21][CH:20]=3)=[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[NH:9]2)=[CH:5][CH:4]=1.[C:29](N1C=CN=C1)(N1C=CN=C1)=[O:30].C1CCN2C(=NCCC2)CC1.Cl>O1CCCC1>[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([CH2:18][C:19]3[N:24]=[C:23]([C:25]4[NH:26][C:29](=[O:30])[O:28][N:27]=4)[CH:22]=[CH:21][CH:20]=3)=[C:8]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)[NH:9]2)=[CH:5][CH:4]=1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: COc1ccc2c(Cc3cccc(C(N)=NO)n3)c(-c3ccccc3)[nH]c2c1
Agent: Cl
Solvent: C1CCC2=NCCCN2CC1
Solvent: C1CCOC1
Product: COc1ccc2c(Cc3cccc(-c4noc(=O)[nH]4)n3)c(-c3ccccc3)[nH]c2c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 86.1 %

Procedure:
Under an argon atmosphere, to a solution of 6-(6-methoxy-2-phenyl-1H-indol-3-ylmethyl)pyridine-2-carboxamidoxime (46.9 mg) in tetrahydrofuran (0.63 mL) were added 1,1′-carbonyldiimidazole (24.5 mg) and 1,8-diazabicyclo[5,4,0]-7-undecene (0.019 mL), and this mixture was stirred at room temperature for 3 hours. 1,1′-Carbonyldiimidazole (16.3 mg) was added thereto, followed by stirring for 80 minutes. Then, 1,8-diazabicyclo[5,4,0]-7-undecene (0.019 mL) was added thereto, followed by stirring for additional 1 hour. To the reaction mixture was added 1 mol/L hydrochloric acid, followed by extraction with ethyl acetate. The organic layer was washed with 1 mol/L hydrochloric acid, a saturated aqueous sodium hydrogen carbonate solution, and saturated brine successively, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: methanol-dichloromethane) to obtain the title compound (43.2 mg).
Reaction SMILES: [Br:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([F:10])[C:3]=1[CH:4]=[O:5].[CH3:11][Si:12]([C:15]#[CH:16])([CH3:14])[CH3:13].C(N(CC)CC)C.O>CN(C)C=O.[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>[Br:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([F:10])[C:3]=1[CH:4]=[O:5].[F:10][C:6]1[CH:7]=[CH:8][CH:9]=[C:2]([C:16]#[C:15][Si:12]([CH3:14])([CH3:13])[CH3:11])[C:3]=1[CH:4]=[O:5]
Reactant: C#C[Si](C)(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Agent: O=Cc1c(F)cccc1Br
Solvent: CCN(CC)CC
Solvent: O
Solvent: CN(C)C=O
Product: C[Si](C)(C)C#Cc1cccc(F)c1C=O
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
A solution of 2-bromo-6-fluorobenzaldehyde (3.3 g, 16 mmol) and (trimethylsilyl)acetylene (4.5 mL, 32 mmol) in anhydrous N,N-dimethylformamide (60 mL) was treated with triethylamine (3.5 mL, 25 mmol), copper(I) iodide (0.3 g, 1.6 mmol), and Pd(PPh3)2Cl2 (0.6 g, 0.80 mmol) under argon atmosphere. The mixture was stirred at RT for 2.5 h. The mixture was poured into water (150 mL) and extracted with ethyl acetate (2×150 mL). The combined organic layers were washed with water (2×75 mL), brine (100 mL) then dried over anhydrous sodium sulfate and evaporated to yield the crude product which was purified by silica gel chromatography (20-30% EtOAc in hexanes) to give 2-fluoro-6-(2-(trimethylsilyl)ethynyl)benzaldehyde 2-bromo-6-fluorobenzaldehyde as a brown oil. MS (ESI, pos. ion) m/z: 221 (M+1).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([O:16][CH3:17])=[O:15])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.Br[CH2:19][CH2:20][O:21][C:22]1[CH:31]=[C:30]2[C:25]([CH:26]=[CH:27][CH:28]=[C:29]2[CH2:32][CH2:33][NH:34][C:35](=[O:37])[CH3:36])=[CH:24][CH:23]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CS(C)=O.CC(=O)CC.O>[C:35]([NH:34][CH2:33][CH2:32][C:29]1[CH:28]=[CH:27][CH:26]=[C:25]2[C:30]=1[CH:31]=[C:22]([O:21][CH2:20][CH2:19][O:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]3[CH:13]=[CH:12][C:11]([C:14]([O:16][CH3:17])=[O:15])=[CH:10][CH:9]=3)=[CH:6][CH:7]=1)[CH:23]=[CH:24]2)(=[O:37])[CH3:36]
Reactant: CC(=O)NCCc1cccc2ccc(OCCBr)cc12
Reactant: COC(=O)c1ccc(-c2ccc(O)cc2)cc1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Solvent: CCC(C)=O
Product: COC(=O)c1ccc(-c2ccc(OCCOc3ccc4cccc(CCNC(C)=O)c4c3)cc2)cc1

Procedure:
In a 100 ml round-bottomed flask, 0.003 mol of methyl 4′-hydroxy[1,1′-biphenyl]-4-carboxylate and 0.003 mol of the compound obtained in Step A are dissolved in a mixture of 3 ml of dimethyl sulphoxide and 20 ml of butanone. 0.009 mol of potassium carbonate and one potassium iodide crystal are added and then the mixture is heated at reflux for 12 hours. The reaction mixture is then cooled and poured into 100 ml of water. The precipitate that forms is suctioned off and recrystallised to yield the title product.
Reaction SMILES: Cl[C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[C:5]([C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=1[Cl:25])[N:6]2[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=1.[CH:26]([NH:29][C:30]1([C:36]([NH2:38])=[O:37])[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1)([CH3:28])[CH3:27].C(N(CC)CC)C.CO.C(Cl)Cl>C(O)C.C(Cl)Cl>[Cl:17][C:14]1[CH:13]=[CH:12][C:11]([N:6]2[C:5]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=3[Cl:25])=[N:4][C:3]3[C:7]2=[N:8][CH:9]=[N:10][C:2]=3[N:33]2[CH2:32][CH2:31][C:30]([NH:29][CH:26]([CH3:28])[CH3:27])([C:36]([NH2:38])=[O:37])[CH2:35][CH2:34]2)=[CH:16][CH:15]=1
Reactant: Clc1ccc(-n2c(-c3ccc(Cl)cc3Cl)nc3c(Cl)ncnc32)cc1
Reactant: CC(C)NC1(C(N)=O)CCNCC1
Solvent: ClCCl
Solvent: CO
Solvent: CCN(CC)CC
Product: CC(C)NC1(C(N)=O)CCN(c2ncnc3c2nc(-c2ccc(Cl)cc2Cl)n3-c2ccc(Cl)cc2)CC1
Temperature: 60 °C

Procedure:
6-Chloro-9-(4-chlorophenyl)-8-(2,4-dichlorophenyl)-9H-purine I-(1A-1)d (300 mg, 0.58 mmol) and 4-isopropylamino-piperidine-4-carboxylic acid amide (101 mg, 0.548 mmol) were suspended in ethanol/methylene chloride (3 ml/1 ml). Triethylamine (0.16 ml, 1.1 mmol) was added to the suspension and the mixture heated to 60° C. until the TLC determined complete (3 h). The reaction mixture was partitioned between saturated NaHCO3 solution and methylene chloride. The organic layer was dried (Na2SO4), filtered, and concentrated to dryness. The pure free base was isolated by silica gel chromatography using 2–4% methanol/methylene chloride as the gradient eluant to afford title compound 10A-1. A solution of the material in methylene chloride was treated with excess 1 N HCl in diethyl ether, stirred, evaporated to dryness, and then triturated in diethyl ether to afford the hydrochloride salt of compound 10A-1 as a tan solid (115 mg, 38%): +ESI MS (M+1) 558.2; 1H NMR (400 MHz, CD3OD) δ 8.40 (s, 1H), 7.60 (d, J=8.3 Hz, 1H), 7.56 (d, J=2.1 Hz, 1H), 7.51–7.44 (m, 3H), 7.33 (d, J=8.7 Hz, 2H), 5.20 (v br m, 2H), 3.87 (br m, 2H), 3.59 (septuplet, J=6.6 Hz, 1H), 2.68 (br d, J=13.7 Hz, 2H), 2.16 (ddd, J=14.5, 10.4, 4.1 Hz, 2H), 1.39 (d, J=6.6 Hz, 6H).
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[CH:9][C:8]([CH3:11])=[C:7]2[C:3]=1[C:4](=[O:13])[CH2:5][C:6]2=[O:12].[N+:14]([O-])([OH:16])=[O:15]>CCOCC>[CH3:11][C:8]1[CH:9]=[CH:10][C:2]([CH3:1])=[C:3]2[C:7]=1[C:6](=[O:12])[CH:5]([N+:14]([O-:16])=[O:15])[C:4]2=[O:13]
Reactant: O=[N+]([O-])O
Reactant: Cc1ccc(C)c2c1C(=O)CC2=O
Solvent: CCOCC
Product: Cc1ccc(C)c2c1C(=O)C([N+](=O)[O-])C2=O

Procedure:
4,7-Dimethyl indane-1,3-dione (0.52 g; 0.003 mole) in dry ether (5 ml) was nitrated with fuming nitric acid (1.0 ml) as described in Example 12 to give 4,7-dimethyl-2-nitro-indane-1,3-dione, m.p. (water, hydrochloric acid) 108°-110°C, (Found: C, 60.07; H, 4.20; N, 6.29; C11H9NO4 requires: C, 60.28; H, 4.14; N, 6.39%).
Reaction SMILES: Br[C:2]1[C:3](=[O:35])[N:4]([CH2:19][C@H:20]([NH:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)[C:5](=[O:18])[N:6]([CH2:9][C:10]2[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=2[F:17])[C:7]=1[CH3:8].[F:36][C:37]1[C:42]([O:43][CH3:44])=[CH:41][CH:40]=[CH:39][C:38]=1B(O)O>CCO.COCCOC>[C:31]([O:30][C:28]([NH:27][C@H:20]([CH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1)[CH2:19][N:4]1[C:3](=[O:35])[C:2]([C:38]2[CH:39]=[CH:40][CH:41]=[C:42]([O:43][CH3:44])[C:37]=2[F:36])=[C:7]([CH3:8])[N:6]([CH2:9][C:10]2[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=2[F:17])[C:5]1=[O:18])=[O:29])([CH3:34])([CH3:33])[CH3:32]
Reactant: COc1cccc(B(O)O)c1F
Reactant: Cc1c(Br)c(=O)n(C[C@H](NC(=O)OC(C)(C)C)C2CCCCC2)c(=O)n1Cc1c(F)cccc1F
Solvent: CCO
Solvent: COCCOC
Product: COc1cccc(-c2c(C)n(Cc3c(F)cccc3F)c(=O)n(C[C@H](NC(=O)OC(C)(C)C)C3CCCCC3)c2=O)c1F
Temperature: 80 °C
Yield: 32.3 %

Procedure:
5-Bromo-3-[2(R)-tert-butoxycarbonylamino-2-cyclohexylethyl]-1-[2,6-difluorobenzyl]-6-methyl-pyrimidine-2,4(1H,3H)-dione 2b (1.0 g, 1.79 mmol) in bezene/EtOH/ethylene glycol dimethyl ether (20/2/22 mL) was added 2-fluoro-3-methoxyphenylboronic acid (382 mg, 2.24 mmol) and saturated Ba(OH)2/water (˜0.5 M, 15 mL). The reaction mixture was deoxygenated with N2 for 10 minutes, tetrakis(triphenylphosine) palladium (0) (208 mg, 0.18 mmol) was added and the reaction mixture was heated at 80° C. overnight under N2. The reaction mixture was partitioned between brine and EtOAc. The organic layer was dried (sodium sulfate), evaporated, and purified by flash chromatography (silica, 30% EtOAc/hexanes) to give compound 2c (348 mg, 32.3%). MS (CI) m/z 502.20 (MH+-Boc).
Reaction SMILES: [OH:1][CH2:2][C@H:3]1[C@@H:6]([N:7]2[C:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[C:10]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[O:9][C:8]2=[O:24])[C:5](=[O:25])[N:4]1CC1C=CC(OC)=CC=1OC.[S:37](Cl)([CH3:40])(=[O:39])=[O:38].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>>[S:37]([O:1][CH2:2][C@H:3]1[C@@H:6]([N:7]2[C:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[C:10]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[O:9][C:8]2=[O:24])[C:5](=[O:25])[NH:4]1)(=[O:39])(=[O:38])[CH3:40]
Reactant: COc1ccc(CN2C(=O)[C@H](n3c(-c4ccccc4)c(-c4ccccc4)oc3=O)[C@@H]2CO)c(OC)c1
Reactant: CS(=O)(=O)Cl
Agent: Cc1ccc(S(=O)(=O)Cl)cc1
Product: CS(=O)(=O)OC[C@@H]1NC(=O)[C@@H]1n1c(-c2ccccc2)c(-c2ccccc2)oc1=O
Yield: 73 %

Procedure:
When cis-2-hydroxymethyl-1-(2,4-dimethoxybenzyl)-3-(4,5-diphenyl-2-oxo-4-oxazolin-3-yl)-4-oxoazetidine is reacted according to Example 13 except that mesyl chloride is substituted for p-toluenesulfonyl chloride, cis-3-(4,5-diphenyl-2-oxo-4-oxazolin-3-yl)-4-oxo-2-azetidinylmethyl mesylate is obtained; 73% yield, mp 185°-8° from ethyl acetate-hexane.
Reaction SMILES: ClCCl.[NH2:4][C@H:5]([CH2:10][OH:11])[CH2:6][CH:7]([CH3:9])[CH3:8].C(N(CC)CC)C.[Si:19](Cl)([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20]>CN(C1C=CN=CC=1)C.O>[Si:19]([O:11][CH2:10][C@@H:5]([NH2:4])[CH2:6][CH:7]([CH3:9])[CH3:8])([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20]
Reactant: CC(C)C[C@H](N)CO
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: CN(C)c1ccncc1
Solvent: O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)C[C@H](N)CO[Si](C)(C)C(C)(C)C
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a room temperature dichloromethane (100 mL) solution of L-leucinol (6.0 g) was added triethylamine (11 mL), DMAP (0.1 g) and t-butyldimethylsilyl chloride (8.5 g). The mixture was stirred at room temperature for 2 hours and then water was added. The organic layer was separated and the aqueous further extracted with dichloromethane. The combined organic layers were washed with brine, dried with magnesium sulfate and the solvent was removed in vacuo to yield the title compound, a residue which was used as such in the next reaction. 1H NMR (CD3COCD3) δ 3.48 (m, 2H), 3.32 (m, 1H), 2.76 (m, 1H), 1.78 (m, 1H), 1.22-1.02 (m, 2H), 0.88 (m, 15H), 0.06 (s, 6H).
Reaction SMILES: C[O:2][C:3](=[O:32])[C:4]1[CH:9]=[CH:8][C:7]([C:10]#[C:11][CH:12]([C:18]2[CH:27]=[CH:26][C:25]3[C:24]([CH3:29])([CH3:28])[CH2:23][CH2:22][C:21]([CH3:31])([CH3:30])[C:20]=3[CH:19]=2)[CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])=[CH:6][CH:5]=1.[OH-].[K+].C1COCC1.Cl>C(O)C.O>[CH3:28][C:24]1([CH3:29])[CH2:23][CH2:22][C:21]([CH3:30])([CH3:31])[C:20]2[CH:19]=[C:18]([CH:12]([CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[C:11]#[C:10][C:7]3[CH:8]=[CH:9][C:4]([C:3]([OH:32])=[O:2])=[CH:5][CH:6]=3)[CH:27]=[CH:26][C:25]1=2
Reactant: CCCCCC(C#Cc1ccc(C(=O)OC)cc1)c1ccc2c(c1)C(C)(C)CCC2(C)C
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Solvent: CCO
Product: CCCCCC(C#Cc1ccc(C(=O)O)cc1)c1ccc2c(c1)C(C)(C)CCC2(C)C
Temperature: 45 °C
Yield: 49.2 %

Procedure:
The ester (609 mg) was dissolved in 9 ml of ethanol and treated with 1.59 g of potassium hydroxide in 6 ml of water. The heterogeneous mixture was further treated with 4 ml of THF and the resulting clear solution was heated to 45° C. for 1.5 hour. The mixture was diluted with 20 ml of water and the pH was adjusted to 2 with HCl 25%. The mixture was extracted with 3 portions of 25 ml of ethyl acetate. The combined organic extracts were dried over MgSO4 and concentrated in vacuo. The resulting orange oil was purified by flash chromatography (SiO2, 25% ethyl/hexanes) followed by trituration in pentane, giving 290 mg of (RS)-4-[3-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-oct-1-ynyl]-benzoic acid as a white solid, m.p. 115-116° C.
Reaction SMILES: [CH:1]12[C:15](=[O:16])[NH:14][C:13](=[O:17])[CH:2]1[C:3]1[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][C:11]2=3)[CH:6]=[CH:5][CH:4]=1.[K].S(C1C=CC(C)=CC=1)(O)(=O)=O.O[CH2:31][CH2:32][N:33]1[C:37]([N+:38]([O-:40])=[O:39])=[CH:36][N:35]=[C:34]1[CH3:41]>O>[CH3:41][C:34]1[N:33]([CH2:32][CH2:31][N:14]2[C:13](=[O:17])[CH:2]3[C:3]4[C:12]5[C:7](=[CH:8][CH:9]=[CH:10][C:11]=5[CH:1]3[C:15]2=[O:16])[CH:6]=[CH:5][CH:4]=4)[C:37]([N+:38]([O-:40])=[O:39])=[CH:36][N:35]=1
Reactant: O=C1NC(=O)C2c3cccc4cccc(c34)C12
Reactant: Cc1ncc([N+](=O)[O-])n1CCO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [K]
Solvent: O
Product: Cc1ncc([N+](=O)[O-])n1CCN1C(=O)C2c3cccc4cccc(c34)C2C1=O

Procedure:
Acenaphthene-1,2-dicarboximide is converted to the potassium salt and reacted with 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole tosylate according to the procedure described in Example 13. The crude reaction mixture is cooled and diluted with water, and then extracted with toluene. The solvent is evaporated from the toluene extract and the residue recrystallized from ethanol to give N-[2-(2-methyl-5-nitro-1-imidazolyl)ethyl]-acenaphthene-1,2-dicarboximide melting at about 183°-185° C.
Reaction SMILES: Cl.[Si]([O:9][C@H:10]1[CH2:14][CH2:13][N:12]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=2)[C:11]1=[O:23])(C(C)(C)C)(C)C>C(Cl)Cl>[OH:9][C@H:10]1[CH2:14][CH2:13][N:12]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=2)[C:11]1=[O:23]
Reactant: Cc1ccc(CN2CC[C@H](O[Si](C)(C)C(C)(C)C)C2=O)cc1
Agent: Cl
Solvent: ClCCl
Product: Cc1ccc(CN2CC[C@H](O)C2=O)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 88.9 %

Procedure:
HCl (4 M in 1,4-dioxane, 25.5 ml, 102 mmol) was added in one portion to a solution of (S)-3-((tert-butyldimethylsilyl)oxy)-1-(4-methylbenzyl)pyrrolidin-2-one (6.53 g, 20.44 mmol, intermediate H) in anyhdrous DCM (20.4 mL) at rt. A slight exotherm was noted. The reaction mixture was allowed to stir at rt for 2 h and then evaporated in vacuo. The residue was taken up in DCM (100 mL) and washed with a satd. sodium bicarbonate solution (100 mL) and brine (50 mL), and then the solution was dried over MgSO4 and concentrated to a residue. The crude product was purified by silica gel chromatography (120 g of silica) eluting with a gradient of 40% to 100% ethyl acetate in hexanes to provide 3.73 g (89%) of the desired product. LC/MS (Conditions B), RT=2.338 min, (M+H)+=206.2. 1H NMR (400 MHz, chloroform-d) δ 7.26-7.02 (m, 4H), 4.43 (d, J=3.5 Hz, 2H), 4.41-4.37 (m, 1H), 3.66 (d, J=2.6 Hz, 1H), 3.34-3.05 (m, 2H), 2.41 (dddd, J=12.8, 8.4, 6.6, 2.2 Hz, 1H), 2.34 (s, 3H), 1.93 (dq, J=12.8, 8.8 Hz, 1H).
Reaction SMILES: [CH2:1]([O:8][C:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[CH2:17][CH:18]([CH:26]([CH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1)[OH:27])[C:19]([O:21]C(C)(C)C)=[O:20])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>FC(F)(F)C(O)=O.ClCCl>[CH2:1]([O:8][C:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[CH2:17][CH:18]([CH:26]([CH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1)[OH:27])[C:19]([OH:21])=[O:20])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)C(Cc1ccccc1C(=O)OCc1ccccc1)C(O)C1CCCCC1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: O=C(OCc1ccccc1)c1ccccc1CC(C(=O)O)C(O)C1CCCCC1
Reaction time: 5 h
Yield: 40 %

Procedure:
t-Butyl 2-(2-benzyloxycarbonylphenylmethyl)-3-cyclohexyl-3-hydroxypropionate (100 mg) was dissolved in a solution of 10% trifluoroacetic acid in dichloromethane (1 ml) and the mixture was stirred for 5 hours. The solution was evaporated under reduced pressure and the residue was purified by chromatography [eluting with methanol-dichloromethane (1:19)] to give 2-(2-benzyloxycarbonyl-phenylmethyl)-3-cyclohexyl-3-hydroxypropionic acid (35 mg).
Reaction SMILES: [CH2:1]([O:4][C:5]1[C:6]([CH2:11]O)=[N:7][CH:8]=[CH:9][CH:10]=1)[CH:2]=[CH2:3].C(N(CC)CC)C.CS([Cl:24])(=O)=O.O>ClCCl>[CH2:1]([O:4][C:5]1[C:6]([CH2:11][Cl:24])=[N:7][CH:8]=[CH:9][CH:10]=1)[CH:2]=[CH2:3]
Reactant: CS(=O)(=O)Cl
Reactant: C=CCOc1cccnc1CO
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: O
Product: C=CCOc1cccnc1CCl
Temperature: 25 °C
Reaction time: 8 h
Yield: 76.7 %

Procedure:
(3-Allyloxy-pyridin-2-yl)-methanol (34 g, 205.8 mmol) is dissolved in dichloromethane (340 mL) under nitrogen and triethylamine (34.4 mL, 247 mmol) is added at 22° C. The mixture is warmed to room temperature in a water bath and methanesulfonyl chloride (16.7 mL, 216 mmol) is added keeping the temperature below 30° C. The reaction is allowed to stir overnight at room temperature. Water (500 mL is added and the mixture stirred for 10 min. The organic portion is separated and washed with a solution of saturated NaHCO3 (100 mL). The organic portion is dried over sodium sulfate, filtered, and the solvent evaporated. The resulting residue is dried under vacuum to constant weight to afford the title compound (29 g, 79%). LC-ES/MS m/z: 184.6 [M+H]+.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[C:7]1([C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH2:10][O:9]1)=O.Cl>O1CCCC1.CCOCC.O.C(OC(=O)C)C>[CH2:7]1[O:9][CH2:10][C:11]2[C:16]1=[CH:15][CH:14]=[CH:13][CH:12]=2
Reactant: O=C1OCc2ccccc21
Agent: Cl
Agent: [Al+3]
Agent: [H-]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CCOCC
Product: c1ccc2c(c1)COC2

Procedure:
Lithium aluminum hydride (0.2 g) was added to approximately 40 ml of dry tetrahydrofuran at room temperature under nitrogen. 3-[4'-(dimethyl)amino-1'-phenyl)-3-(3",5"-diisopropyl-4"-oxo-1"-phenyl)phthalide (1.0 g) was dissolved in 40 ml dry tetrahydrofuran and the solution added dropwise to the lithium aluminum hydride suspension. The temperaturerose to about 30° C. Upon completion of addition, a sample of the reaction mixture was poured into water and extracted with ether. TLC on silica gel with 1:1 ether/petroleum ether showed completion of the reaction and no unreacted phthalide. After neutralizing the lithium aluminum hydride with ethylacetate, the reaction mixture was poured into 200 ml water, the pH adjusted to 3 with HCl and extracted with ether. The ether layer was washed with 200 ml of 5% aqueous sodium hydroxide, dried over sodium sulfate and the ether evaporated to leave a pink-red residue. The residue was dissolved in about 20 ml ether, and petroleum ether was added to precipitate a white solid. The solution after filtering was evaporated to give the corresponding phthalan as a pink solid.