Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:12]2[NH:13][C:14]3[CH:15]=[C:16]([OH:20])[CH:17]=[CH:18][C:19]=3[C:11]=2[C:10]([CH3:22])([CH3:21])[CH2:9][N:8]([C:23](=[O:31])[C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)[CH:7]=1)=[O:5])[CH3:2].[I-].[Na+].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:41][CH2:42][N:43]1[CH2:48][CH2:47][O:46][CH2:45][CH2:44]1>CC(C)=O>[CH2:1]([O:3][C:4]([C:6]1[C:12]2[NH:13][C:14]3[CH:15]=[C:16]([O:20][CH2:41][CH2:42][N:43]4[CH2:48][CH2:47][O:46][CH2:45][CH2:44]4)[CH:17]=[CH:18][C:19]=3[C:11]=2[C:10]([CH3:22])([CH3:21])[CH2:9][N:8]([C:23](=[O:31])[C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)[CH:7]=1)=[O:5])[CH3:2]
Reactant: CCOC(=O)C1=CN(C(=O)c2ccc(F)cc2)CC(C)(C)c2c1[nH]c1cc(O)ccc21
Reactant: ClCCN1CCOCC1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCOC(=O)C1=CN(C(=O)c2ccc(F)cc2)CC(C)(C)c2c1[nH]c1cc(OCCN3CCOCC3)ccc21
Temperature: 75 °C
Yield: 10.3 %

Procedure:
A mixture of 3-(4-fluorobenzoyl)-8-hydroxy-1,1-dimethyl-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylic acid ethyl ester (85 mg, 0.2 mmol), sodium iodide (30 mg), potassium carbonate (140 mg, 1.01 mmol) and 4-(2-chloroethyl)morpholine (free base, 300 mg, 2 mmol) and acetone (8 mL) was heated at 75° C. for 24 hours. The solid was filtered off, and the filtrate was concentrated in vacuo, and the crude product was purified by reverse-phase preparative HPLC to give the title compound (11 mg); 1H-NMR (CDCl3): δ 10.51 (1H, s), 7.72 (1H, s), 7.67 (1H, d), 7.66-7.59 (2H, m), 7.15-7.10 (2H, m), 6.86 (1H, d), 6.76 (1H, dd), 4.27-4.17 (4H, m), 4.08 (2H, br s), 3.77 (4H, m), 2.88 (2H, br s), 2.65 (4H, br s), 1.59 (6H, s), 1.25 (3H, t); MS (ES): 536 (MH+).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[C:8]([C:10](=[O:13])[CH2:11][CH3:12])[CH:7]=[CH:6][C:5]=1[NH:14]C(=O)C)([O-:3])=[O:2].N>Cl>[NH2:14][C:5]1[CH:6]=[CH:7][C:8]([C:10](=[O:13])[CH2:11][CH3:12])=[CH:9][C:4]=1[N+:1]([O-:3])=[O:2]
Reactant: CCC(=O)c1ccc(NC(C)=O)c([N+](=O)[O-])c1
Agent: Cl
Agent: N
Product: CCC(=O)c1ccc(N)c([N+](=O)[O-])c1
Yield: 90.1 %

Procedure:
A solution of N-(2-nitro-4-propionylphenyl)acetamide (3.36 g, 10 mmol) in 30 mL 35% HCl was heated to reflux for 1 h and cooled. The pH was adjusted to 7 by adding aqueous ammonia under stirring. The precipitate was collected by filtration to give the desired product as a yellow solid (1.75 g, 90%).
Reaction SMILES: CC1C=CC(C=O)=CC=1.[C:10]1([B-:16]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C[C:36]1[CH:41]=[CH:40][N+:39]([CH3:42])=[CH:38][CH:37]=1>N1CCCCC1.C(O)C>[C:29]1([B-:16]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1.[CH3:42][N+:39]1[CH:40]=[CH:41][CH:36]=[CH:37][CH:38]=1
Reactant: Cc1cc[n+](C)cc1
Agent: Cc1ccc(C=O)cc1
Agent: c1ccc([B-](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCNCC1
Solvent: CCO
Product: C[n+]1ccccc1

Procedure:
In a 500-mL one-neck flask fitted with a stirrer and a condenser, 1.2 g (0.01 mol) of 4-methylbenzaldehyde, 0.01 mol of 4-methyl-N-methylpyridinium tetraphenylborate, and 30 mL of absolute ethanol were mixed. Five drops of piperidine was added to the mixture. The solution was then heated to reflux, refluxed overnight, cooled, and filtered. The collected solid was washed twice with ether and twice with water to obtain 4-[p-N-methyl-N-ethylamino)styryl]-N-methylpyridinium tetraphenylborate in 78% yield as a reddish solid.
Reaction SMILES: C([Li])CCC.[CH:6]([Si:9]([C:16]#[CH:17])([CH:13]([CH3:15])[CH3:14])[CH:10]([CH3:12])[CH3:11])([CH3:8])[CH3:7].CON(C)[C:21](=[O:30])[CH2:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C1COCC1>[C:24]1([CH2:23][CH2:22][C:21](=[O:30])[C:17]#[C:16][Si:9]([CH:10]([CH3:11])[CH3:12])([CH:6]([CH3:8])[CH3:7])[CH:13]([CH3:15])[CH3:14])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: C#C[Si](C(C)C)(C(C)C)C(C)C
Reactant: CON(C)C(=O)CCc1ccccc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CC(C)[Si](C#CC(=O)CCc1ccccc1)(C(C)C)C(C)C
Temperature: 0 °C
Reaction time: 1 h

Procedure:
Following a procedure of Trost (Trost, B. M. et al., J. Am. Chem. Soc. 128, 6745-6754 (2006)); n-Butyllithium (2.5 M in hexanes, 10.4 ml, 26 mmol, 1.7 eq.) was added dropwise to a solution of triisopropylsilyl acetylene (5.8 ml, 26 mmol, 1.7 eq.) in THF (53 ml) at −78° C. After addition, the mixture was allowed to warm slowly to 0° C. and stirred for 1 h. The mixture was cooled to −78° C. and a solution of 83 (3.0 g, 15.3 mmol, 1 eq.) in THF (20 ml) was added dropwise. The mixture was then allowed to slowly warm to −10° C. and stirred for 1 h before being quenched by the addition of saturated aq. NH4Cl (50 ml). The mixture was extracted with EtOAc (3×30 ml) and the combined organic phases were washed with brine (50 ml) before being dried (MgSO4), filtered and concentrated to give the crude product. This was purified by column chromatography on silica, eluting with petrol/Et2O (100:0 to 98:2), giving the title product 84 as a clear, colourless oil (4.61 g, 96%).
Reaction SMILES: P(Cl)(Cl)(Cl)=O.CN(C)[CH:8]=[O:9].[NH:11]1[C:19]2[C:14](=[CH:15][C:16]([C:20]([O:22][CH3:23])=[O:21])=[CH:17][CH:18]=2)[CH:13]=[CH:12]1.C(=O)([O-])[O-].[K+].[K+]>O>[CH:8]([C:13]1[C:14]2[C:19](=[CH:18][CH:17]=[C:16]([C:20]([O:22][CH3:23])=[O:21])[CH:15]=2)[NH:11][CH:12]=1)=[O:9]
Reactant: CN(C)C=O
Reactant: COC(=O)c1ccc2[nH]ccc2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O=P(Cl)(Cl)Cl
Solvent: O
Product: COC(=O)c1ccc2[nH]cc(C=O)c2c1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
A 1.28 ml portion of phosphoryl chloride was added dropwise to 8 ml of N,N-dimethylformamide under ice-cooling, followed by stirring at room temperature for 15 minutes. An 8 ml portion of an N,N-dimethylformamide solution of 2.00 g of methyl 1H-indole-5-carboxylate was added dropwise to this solution under ice-cooling, followed by stirring at room temperature for 1.5 hours. Under ice-cooling, 50 ml of water was added thereto and potassium carbonate was further added until the pH became 12, and the resulting solid was collected by filtration, washed with water and then dried over heating under a reduced pressure to obtain 2.19 g of methyl 3-formyl-1H-indole-5-carboxylate as a pale light brown solid.
Reaction SMILES: C[O:2][C:3]([CH:5]1[CH:10]([O:11]C(=O)C)[CH:9]([O:15]C(=O)C)[CH:8]([O:19]C(=O)C)[CH:7]([O:23][C:24](=[O:49])[NH:25][CH2:26][CH2:27][C:28]2[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[N:30]([S:37]([C:40]3[N:47]4[C:43]([S:44][CH:45]=[CH:46]4)=[N:42][C:41]=3[Cl:48])(=[O:39])=[O:38])[CH:29]=2)[O:6]1)=[O:4].CO.O[Li].O>C1COCC1.O>[Cl:48][C:41]1[N:42]=[C:43]2[N:47]([C:40]=1[S:37]([N:30]1[C:31]3[C:36](=[CH:35][CH:34]=[CH:33][CH:32]=3)[C:28]([CH2:27][CH2:26][NH:25][C:24]([O:23][C@@H:7]3[O:6][C@H:5]([C:3]([OH:4])=[O:2])[C@@H:10]([OH:11])[C@H:9]([OH:15])[C@H:8]3[OH:19])=[O:49])=[CH:29]1)(=[O:38])=[O:39])[CH:46]=[CH:45][S:44]2
Reactant: COC(=O)C1OC(OC(=O)NCCc2cn(S(=O)(=O)c3c(Cl)nc4sccn34)c3ccccc23)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O
Agent: [Li]O
Solvent: O
Solvent: CO
Solvent: C1CCOC1
Product: O=C(NCCc1cn(S(=O)(=O)c2c(Cl)nc3sccn23)c2ccccc12)O[C@@H]1O[C@H](C(=O)O)[C@@H](O)[C@H](O)[C@H]1O
Temperature: 0 °C
Reaction time: 2 h
Yield: 86 %

Procedure:
A solution of 3,4,5-triacetoxy-6-(2-{1-[(6-chloroimidazo[2,1-b][1,3]thiazol-5-yl)sulfonyl]-1H-indol-3-yl}ethycarbamoyloxy)tetrahydropyran-2-carboxylic acid methyl ester (1.0 g, 1.35 mmol) in THF is treated with CH3OH (38.8 mL) and H2O (10 mL), cooled to 0° C. (ice-water bath), treated with a solution of LiOH.H2O (340 mg, 8.1 mmol, 6 eq) in H2O (5.5 mL) [0.1 N LiOH/MeOH/THF/H2O] and stirred at 0° C. for 2 h under N2 atmosphere. Progress of the deprotection is monitored via reversed-phase TLC (SiO2—C18 MeCN/H2O, 3/7). The reaction mixture is diluted with 150 mL of H2O, neutralized by the addition of 10 g of amberlite-120 (plus) cation exchange material (H+ form) and filtered. The filtrate is concentrated under reduced pressure to an aqueous suspension. This suspension is freeze dried and lyophilized to give the title product, 700 mg (86% yield). Further purification by silica gel column chromatography [CHCl3/CH3OH/H2O (7:3:0.5) as a eluent] provides the title product, 310 mg, 98% pure, identified by mass spectral and NMR analyses. 1H NMR (300 MHz, DMSO-d6): 8.31 (d, 1H, J=4.5 Hz), 7.94-7.91 (m, 1H), 7.82 (s, 1H), 7.69 (d, 1H, J=4.2 Hz), 7.64-7.57 (m, 2H), 7.39-7.27 (m, 2H), 5.31 (d, 1H, J=8.1 Hz), 3.69 (d, 1H, J=9.0 Hz), 3.37-3.13 (m, 5H), 2.82 (t, 2H, J=7.0 Hz); 13C (75 MHz, DMSO-d6): 170.6, 155.4, 155.3, 152.3, 139.2, 134.9, 131.6, 125.7, 124.5, 124.4, 121.1, 121.1, 120.7, 118.8, 116.6, 113.8, 95.5, 76.6, 76.5, 72.8, 72.0, 25.2; LC/MS (ESI) retention time=35.12, [M+H]+=600.7.
Reaction SMILES: Cl[S:2]([C:5]1[CH:14]=[CH:13][C:8]([C:9]([O:11][CH3:12])=[O:10])=[CH:7][CH:6]=1)(=[O:4])=[O:3].[N:15]1[C:24]2[C:19](=[CH:20][C:21]([CH2:25][NH2:26])=[CH:22][CH:23]=2)[CH:18]=[CH:17][CH:16]=1>>[N:15]1[C:24]2[C:19](=[CH:20][C:21]([CH2:25][NH:26][S:2]([C:5]3[CH:14]=[CH:13][C:8]([C:9]([O:11][CH3:12])=[O:10])=[CH:7][CH:6]=3)(=[O:4])=[O:3])=[CH:22][CH:23]=2)[CH:18]=[CH:17][CH:16]=1
Reactant: COC(=O)c1ccc(S(=O)(=O)Cl)cc1
Reactant: NCc1ccc2ncccc2c1
Product: COC(=O)c1ccc(S(=O)(=O)NCc2ccc3ncccc3c2)cc1

Procedure:
The titled compound was prepared according to the procedure described in step-1 of Example 1 from methyl 4-(chlorosulfonyl)benzoate and quinolin-6-ylmethanamine.
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[CH:4][C:3]=1[NH:11][C:12](=[O:21])[CH:13]=[CH:14][C:15]1[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=1.[F:22][C:23]1[CH:29]=[CH:28][C:26]([NH2:27])=[CH:25][CH:24]=1.C(N(CC)CC)C.C(=O)([O-])[O-].[K+].[K+]>ClCCl>[F:22][C:23]1[CH:29]=[CH:28][C:26]([NH:27][C:6](=[O:7])[C:5]2[CH:9]=[CH:10][C:2]([CH3:1])=[C:3]([NH:11][C:12](=[O:21])[CH:13]=[CH:14][C:15]3[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=3)[CH:4]=2)=[CH:25][CH:24]=1
Reactant: Nc1ccc(F)cc1
Reactant: Cc1ccc(C(=O)Cl)cc1NC(=O)C=Cc1cccnc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1ccc(C(=O)Nc2ccc(F)cc2)cc1NC(=O)C=Cc1cccnc1
Reaction time: 0.5 h

Procedure:
To a suspension of the product of step 3 (0.3 g) in anhydrous dichloromethane (30 ml), a solution of 4-fluoroaniline (0.1 g) and triethylamine (0.2 ml) in dichloromethane (15 ml) was added dropwise slowly in an ice-bath with the temperature no more than 5° C. After addition, the reaction was carried out for 30 min in an ice-bath, and then at room temperature overnight. The completion of reaction was indicated by TLC. Potassium carbonate solution (10%) was added. The reaction mixture was extracted with EtOAc (20 ml*3). The organic layer was dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to recover solvent. The residue was purified on a silica gel column using EtOAc/petroleum ether/ethanol (1:2:0.5) as an eluent. The concentration of the eluent and crystallization provided a solid powder.
Reaction SMILES: [Si]([O:18][CH2:19][C@@H:20]1[S:25][CH2:24][C@@H:23]([CH3:26])[NH:22][CH2:21]1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[CH3:26][C@H:23]1[NH:22][CH2:21][C@H:20]([CH2:19][OH:18])[S:25][CH2:24]1
Reactant: C[C@@H]1CS[C@@H](CO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)CN1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: C[C@@H]1CS[C@@H](CO)CN1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of (2R,5R)-2-({[tert-butyl(diphenyl)silyl]oxy}methyl)-5-methylthiomorpholine (1, 0.200 g, 0.519 mmol) in THF (1 mL) was added tetrabutylammonium fluoride (1.0 M in THF, 0.778 mL, 0.778 mmol). The reaction was stirred at ambient temperature for 2 h, then concentrated in vacuo to provide crude [(2R,5R)-5-methylthiomorpholin-2-yl]methanol (2) that gave a mass ion (ES+) of 148.3 for M+H+.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]([O:17]CC)=[O:16])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>CO>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([CH2:14][C:15]([OH:17])=[O:16])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CCOC(=O)CN1CCN(C(=O)OC(C)(C)C)CC1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CC(C)(C)OC(=O)N1CCN(CC(=O)O)CC1
Reaction time: 4 h

Procedure:
A solution of 4-ethoxycarbonylmethyl-piperazine-1-carboxylic acid tert-butyl ester (1.3 g, 4.78 mmol) in methanol (50 ml) was treated with NaOH (1N, 10 ml, 10 mmol) and stirred for 4 h. The mixture is concentrated and the residue is adjusted to pH 6 with 5% citric acid solution. The mixture is extracted with ethyl acetate, dried over sodium sulfate and concentrated to give 4-carboxymethyl-piperazine-1-carboxylic acid tert-butyl ester, 445 mg (38%) as a white solid. ESI MS m/z 1179 (M+H+); 1H NMR (400 MHz, CDCl3) δ 3.80-3.60 (m, 4H), 3.42 (s, 2H), 3.10-2.84 (m, 4H), 1.24 (s, 9H).
Reaction SMILES: [I:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].[CH2:9]([O:11][C:12](=[O:23])[C:13](=[CH:19]OCC)[C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH3:10]>ClCCl>[CH2:9]([O:11][C:12](=[O:23])[C:13](=[CH:19][NH:4][C:3]1[CH:5]=[CH:6][CH:7]=[CH:8][C:2]=1[I:1])[C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH3:10]
Reactant: CCOC=C(C(=O)OCC)C(=O)OCC
Reactant: Nc1ccccc1I
Solvent: ClCCl
Product: CCOC(=O)C(=CNc1ccccc1I)C(=O)OCC
Temperature: 110 °C
Reaction time: 3 h
Yield: 91.6 %

Procedure:
2-Iodoaniline (50 g, 228.3 mmol) and 2-ethoxymethylene-malonic acid diethyl ester (50 mL, 251.1 mmol) were mixed and the solution was stirred at 110° C. for 3 h. The crude was dissolved in dichloromethane and it was purified by silica plug. The product was eluted with ethyl acetate/hexanes (10–50%) and the solvent removed under reduced pressure to afford 2-[(2-iodo-phenylamino)-methylene]-malonic acid diethyl ester as an off-white powder (81.4 g, 91.6%). 1H NMR (CDCl3, 400 MHz) δ 1.49 (t, 3H), 1.54 (t, 3H), 4.40 (q, 2H), 4.52 (q, 2H), 7.01–7.05 (m, 1H), 7.36–7.39 (m, 1H), 7.52–7.56 (m, 1H), 8.59 (d, 1H). Exact mass calculated for C14H16INO4 389.01, found 390.1 (MH+).
Reaction SMILES: [C:1]([NH:8][CH2:9][CH:10](O)[CH3:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:32]1([O:38][C:39]([NH:41][O:42][C:43]([O:45][C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)=[O:44])=[O:40])[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[C:32]1([O:38][C:39]([N:41]([CH:10]([CH2:9][NH:8][C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH3:11])[O:42][C:43]([O:45][C:46]2[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=2)=[O:44])=[O:40])[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1
Reactant: O=C(NOC(=O)Oc1ccccc1)Oc1ccccc1
Reactant: CC(O)CNC(=O)OC(C)(C)C
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(CNC(=O)OC(C)(C)C)N(OC(=O)Oc1ccccc1)C(=O)Oc1ccccc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 836.9 %

Procedure:
A one liter roundbottom flask was charged with N-Boc-1-amino-2-propanol (26.42 g, 0.0151 mol), triphenylphosphine (41.4 g, 0.158 mol), and N,O-bisphenyloxycarbonylhydroxylamine (43.2 g, 0.158 mol), and dry THF (550 mL). The solution was cooled to 0° C., and diethylazodicarboxylate (24.9 mL, 0.158 mol) was added in THF (50 mL). The reaction was stirred one hour after removing the cooling bath, and concentrated under vacuum. Chromatographic purification is enhanced by adding dichloromethane (200 mL) and concentrating in vacuo twice to remove THF before column chromatography (400 g silica gel, 15% EtOAc/Hex) to provide N,O-bisphenyloxycarbonyl-t-butyloxycarbonylamino-2-propylhydroxylamine (54.4 g, 80%).
Reaction SMILES: [CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][C@H:6]([OH:25])/[CH:7]=[CH:8]/[C@@H:9]1[C@@H:13]([CH2:14]/[CH:15]=[CH:16]\[CH2:17][CH2:18][CH2:19][C:20]([OH:22])=[O:21])[C@@H:12]([OH:23])[CH2:11][C@H:10]1[OH:24].[C:26]1(C)C(C)=CC=CC=1>>[CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][C@:6]([OH:25])(/[CH:7]=[CH:8]/[C@@H:9]1[C@@H:13]([CH2:14]/[CH:15]=[CH:16]\[CH2:17][CH2:18][CH2:19][C:20]([OH:22])=[O:21])[C@@H:12]([OH:23])[CH2:11][C@@H:10]1[OH:24])[CH3:26]
Reactant: CCCCC[C@H](O)/C=C/[C@@H]1[C@@H](C/C=C\CCCC(=O)O)[C@@H](O)C[C@H]1O
Reactant: Cc1ccccc1C
Product: CCCCC[C@](C)(O)/C=C/[C@@H]1[C@@H](C/C=C\CCCC(=O)O)[C@@H](O)C[C@@H]1O

Procedure:
Following the procedure of example 1 but substituting (15S) 15-methyl PGF2α for PGF2α and extending the reaction time in refluxing xylene from 24 hours to 48 hours there is produced crude (15S)-15-methyl PGF2α, 1,15-lactone. The crude lactone is purified by repeated chromatography and, further, if desired, by TLC purification to afford in low yield (15S)-15-methyl-PGF2α, 1,15-lactone in essentially pure form.
Reaction SMILES: [O-]CC.[Na+].[H-].[Na+].Cl.[C:8]([NH2:11])(=[NH:10])[CH3:9].C([O:14][C:15](=O)[CH:16]([C:25]#[N:26])[CH2:17][C:18]1([CH2:23][CH3:24])[O:22][CH2:21][CH2:20][O:19]1)C>>[CH3:9][C:8]1[N:11]=[C:15]([OH:14])[C:16]([CH2:17][C:18]2([CH2:23][CH3:24])[O:22][CH2:21][CH2:20][O:19]2)=[C:25]([NH2:26])[N:10]=1
Reactant: CCOC(=O)C(C#N)CC1(CC)OCCO1
Reactant: CC(=N)N
Agent: CC[O-]
Agent: Cl
Agent: [H-]
Product: CCC1(Cc2c(N)nc(C)nc2O)OCCO1
Temperature: 25 °C
Yield: 13.6 %

Procedure:
A solution of sodium ethoxide (prepared from 0.96 g (40 mmol) of sodium hydride and 40 mL of ethanol) was treated with 3.78 g (40 mmol) of acetamidine hydrochloride and 9.09 g (40 mmol) of a-cyano-2-ethyl-1,3-dioxolane-2-propanoic acid ethyl ester. The mixture was heated to reflux for 150 minutes, cooled to ambient temperature and concentrated under vacuum. The solid residue was dissolved in 50 mL of water and the resulting solution washed with ethyl ether. The product precipitated upon neutralization to pH 7.0 with glacial acetic acid. The precipitate was collected by filtration, washed with water, and dried to 0.70 g (7.5%) of 2-methyl-6-amino-5-(2-ethyl-1,3-dioxolan-2-ylmethyl)-4-pyrimidinol. The filtrate and wash were combined and concentrated. The resulting solid was slurried in ethyl ether and solids collected to provide an additional 1.3 g (14%) of 2-methyl-6-amino-5-(2-ethyl-1,3-dioxolan-2-ylmethyl)-4-pyrimidinol as a tan solid. nmr (500 MHz, dmso-d6) δ0.79 (t, J=7.4 Hz, 3H), 1.51 (q, J=7.4 Hz, 2H), 2.10 (s, 3H), 2.58 (s, 2H), 3.83 (m, 2H), 3.93 (m, 2H), 6.00 (s, 2H), 11.38 (s, 1H)
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[C:14]([O:15]C)=[N:13][C:12]2[C:7]1=[N:8][C:9]([NH:18][C@H:19]([CH3:23])[CH2:20][CH2:21][CH3:22])=[N:10][C:11]=2[NH2:17].[NH:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1>>[NH2:17][C:11]1[N:10]=[C:9]([NH:18][C@H:19]([CH3:23])[CH2:20][CH2:21][CH3:22])[N:8]=[C:7]2[C:12]=1[NH:13][C:14](=[O:15])[N:6]2[CH2:5][CH2:4][CH2:3][CH2:2][N:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1
Reactant: CCC[C@@H](C)Nc1nc(N)c2nc(OC)n(CCCCCl)c2n1
Reactant: C1CCNCC1
Product: CCC[C@@H](C)Nc1nc(N)c2[nH]c(=O)n(CCCCN3CCCCC3)c2n1

Procedure:
Prepared similarly to Example 29 from 9-(4-chlorobutyl)-N2-[(1R)-1-methylbutyl]-8-(methyloxy)-9H-purine-2,6-diamine and piperidine.
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O[CH2:21][CH2:22][C:23]1[CH:28]=[CH:27][C:26]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[CH:25][CH:24]=1.[Br:37]N1C(=O)CCC1=O>ClCCl.CCOCC>[Br:37][CH2:21][CH2:22][C:23]1[CH:28]=[CH:27][C:26]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[CH:25][CH:24]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: CC(C)(C)OC(=O)Nc1ccc(CCO)cc1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: CCOCC
Product: CC(C)(C)OC(=O)Nc1ccc(CCBr)cc1
Temperature: 0 °C
Reaction time: 3 h
Yield: 69.5 %

Procedure:
8.68 g (33.08 mmol) of triphenylphosphine are added, under an argon atmosphere, to a solution of 7.85 g (33.08 mmol) of tert-butyl [4-(2-hydroxyethyl)phenyl]carbamate in 85 mL of dichloromethane. The mixture is cooled to 0° C. and 5.95 g (33.08 mmol) of N-bromosuccinimide are added portionwise over 25 minutes. Stirring is continued for 3 hours at 0° C. The solvent is then evaporated off, the oil obtained is taken up in ether and the precipitate formed is filtered off and discarded. The filtrate is evaporated and the residue is purified by chromatography on silica gel (eluent: 10/90 EtOAc/heptane) to give 6.90 g of tert-butyl [4-(2-bromoethyl)phenyl]carbamate, the characteristics of which are as follows:
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][OH:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].CC1(C)N([O])C(C)(C)CCC1.C(=O)(O)[O-].[Na+].[Cl-].[Na+]>C1(C)C=CC=CC=1.O.C(OCC)(=O)C>[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH:16]=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7]
Reactant: CCCCCCCOCCCCCCCCO
Agent: CC1(C)CCCC(C)(C)N1[O]
Agent: O=C([O-])O
Agent: [Cl-]
Solvent: O
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Product: CCCCCCCOCCCCCCCC=O
Temperature: 0 °C
Reaction time: 2 h
Yield: 93 %

Procedure:
8-Heptyloxy-octan-1-ol (No. 6804253; 193.8 mg, 0.793 mmol) was dissolved in toluene (1.36 mL), and 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO; 1.2 mg, 0.00768 mmol) and an aqueous solution (1.33 mL) of 5% sodium bicarbonate were added in order. The mixture was cooled to 0° C. While maintaining the temperature at 0° C., an aqueous solution (492 μL) of 12% sodium chloride was added. The mixture was stirred at 0° C. for 2.0 minutes and at room temperature for 2.0 hours. TEMPO (2.4 mg, 0.0154 mmol) and an aqueous solution (49.2 μL) of 12% sodium chloride were added further. The mixture was stirred at room temperature for 1 hour. Ethyl acetate and water were added, and the mixture was extracted. The organic layer was washed with water and a saturated brine, dried over anhydrous sodium sulfate, and filtered. The solvent was distilled off. The resulting residue was then purified with SP1 (SiO2 cartridge, 50% ethyl acetate/n-hexane, Rf=0.3) to obtain the target compound, 8-heptyloxy-octanal (ESI (LC/MS positive mode) m/z 243 (M+H); Rt 2.35 min.; 178.0 mg, 93% yield).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[CH3:21])[C:13]2[C:12](=[O:22])[CH2:11][NH:10][CH2:9][C:8]=2[NH:7][C:6]=1[CH3:23])=[O:4].[CH3:24][C:25]1[C:35]([CH3:36])=[CH:34][CH:33]=[CH:32][C:26]=1[O:27][CH2:28][CH:29]1[O:31][CH2:30]1>CO>[CH3:1][O:2][C:3]([C:5]1[CH:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[CH3:21])[C:13]2[C:12](=[O:22])[CH2:11][N:10]([CH2:30][CH:29]([OH:31])[CH2:28][O:27][C:26]3[CH:32]=[CH:33][CH:34]=[C:35]([CH3:36])[C:25]=3[CH3:24])[CH2:9][C:8]=2[NH:7][C:6]=1[CH3:23])=[O:4]
Reactant: Cc1cccc(OCC2CO2)c1C
Reactant: COC(=O)C1=C(C)NC2=C(C(=O)CNC2)C1c1ccccc1C
Solvent: CO
Product: COC(=O)C1=C(C)NC2=C(C(=O)CN(CC(O)COc3cccc(C)c3C)C2)C1c1ccccc1C
Yield: 41.1 %

Procedure:
1,4,5,6,7,8-Hexahydro-2-methyl-4-(2-methylphenyl)-5-oxo-1,7-naphthyridine-3-carboxylic acid methyl ester (14.5 g), 6.8 g of 3-(2,3-dimethylphenoxy)-1,2-epoxypropane and 250 ml of methanol were combined and refluxed for 18 hours. The solvent was removed in vacuo. The residue was dissolved in diethyl ether and saturated with hydrogen chloride. The solid was separated and dried in vacuo at 75° C. for 18 hours. The solid was recrystallized from acetonitrile to obtain 7.7 g of the title compound as the hydrochloride salt, m.p. 220° C. dec.