Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br-].[CH:2]1([P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH2:6][CH2:5][CH2:4][CH2:3]1.[Li]CCCC.[CH3:31][O:32][C:33](=[O:40])[CH2:34][CH2:35][CH2:36][CH2:37][CH:38]=O.O>C1COCC1>[CH3:31][O:32][C:33](=[O:40])[CH2:34][CH2:35][CH2:36][CH2:37][CH:38]=[C:2]1[CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: COC(=O)CCCCC=O
Reactant: c1ccc([P+](c2ccccc2)(c2ccccc2)C2CCCC2)cc1
Agent: [Br-]
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: O
Product: COC(=O)CCCCC=C1CCCC1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 69.5 %

Procedure:
To a stirred suspension of cyclopentyltriphenylphosphonium bromide (10.0 g, 23.8 mmol) in TMF (60 mL) was added dropwise n-BuLi (10.2 mL, 2.5 M solution in hexanes, 23.8 mmol) at 0° C. under N2. The resulting solution was stirred at this temperature for 30 min and cooled to −78 ° C. A solution of 6-oxo-hexanoic acid methyl ester (3.33 g, 23.1 mmol) in THF (6 mL) was added quickly. The resulting mixture was then allowed to warm to room temperature and stirred overnight. Water (30 mL) was added. The aqueous phase was extracted with hexane. The combined organic phases were washed with saturated aqueous NH4Cl and brine and dried. Concentration and purification of the residue by flash chromatography on silica gel (hexane:ethyl acetate, 10:1) afforded 6-cyclopentylidene-hexanoic acid methyl ester (3.15 g, 70%) as a colorless oil: 1H NMR (300 MHz, CDCl3) δ 5.20 (1H, m), 3.64 (3H, s), 2.29 (2H, m), 2.16 (4H, m), 1.96 (2H, m), 1.62 (6H, m), 1.35 (2H, m); 13C NMR (75 MHz, CDCl3) δ 174.26, 143.54, 119.65, 51.66, 34.29, 33.79, 29.44, 28.86, 26.69, 26.61, 24.91.
Reaction SMILES: [O:1]=[C:2]1[C:7]([C:8]([OH:10])=O)=[CH:6][CH:5]=[CH:4][NH:3]1.CN1CCOCC1.ClC(OCC(C)C)=O.[NH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>O1CCCC1>[O:1]=[C:2]1[C:7]([C:8]([NH:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[O:10])=[CH:6][CH:5]=[CH:4][NH:3]1
Reactant: Nc1ccccc1
Reactant: O=C(O)c1ccc[nH]c1=O
Agent: CC(C)COC(=O)Cl
Solvent: C1CCOC1
Solvent: CN1CCOCC1
Product: O=C(Nc1ccccc1)c1ccc[nH]c1=O
Temperature: 0 °C
Reaction time: 6 h
Yield: 97.5 %

Procedure:
To a solution of 2-oxo-1,2-dihydropyridine-3-carboxylic acid (1.00 g, 7.18 mmol) in anhydrous tetrahydrofuran (40 mL) was added 4-methyl morpholine (1.01 g, 10.06 mmol). After cooling to 0° C., isobutyl chloroformate (1.27 g, 9.34 mmol) was added to the reaction mixture. The mixture was stirred at ambient temperature for 6 hours followed by the addition of aniline (0.87 g, 9.34 mmol). The resulting mixture was stirred at ambient temperature for 16 hours. The solvent was removed in vacuo. The residue was dissolved in ethyl acetate (100 mL), and washed with saturated aqueous sodium bicarbonate (2×50 mL) and brine (50 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford the title compound as a colorless solid (1.50 g, 97%): 1H NMR (300 MHz, DMSO-d6) δ 12.71 (br s, 1H), 12.14 (s, 1H), 8.46-8.38 (m, 1H), 7.80-7.52 (m, 1H), 7.65-7.62 (m, 2H), 7.35-7.29 (m, 2H), 7.10-6.95 (m, 1H), 6.58-6.45 (m, 1H); MS (ES+) m/z 215.2 (M+1).
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][CH:10]=[C:9]([N+:13]([O-:15])=[O:14])[C:5]=1[C:6]([OH:8])=[O:7])([O-:3])=[O:2].[CH3:16]N1C=CCN(C2C=CC(C)=CC=2)N1>CCOCC>[N+:1]([C:4]1[CH:12]=[CH:11][CH:10]=[C:9]([N+:13]([O-:15])=[O:14])[C:5]=1[C:6]([O:8][CH3:16])=[O:7])([O-:3])=[O:2]
Reactant: Cc1ccc(N2CC=CN(C)N2)cc1
Reactant: O=C(O)c1c([N+](=O)[O-])cccc1[N+](=O)[O-]
Solvent: CCOCC
Product: COC(=O)c1c([N+](=O)[O-])cccc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 1 h
Yield: 37.3 %

Procedure:
2,6-Dinitrobenzoic acid (10.6 grams) is suspended in ether (125 ml.) at 0°C. 1-Methyl-3-p-tolyltriazine (8.2 grams) in ether (75 ml.) is added dropwise to the stirred reaction mixture in an ice bath. The reaction mixture is stirred at 0° for 1 hour and at room temperature for 1 hour. The reaction mixture is diluted to 1 l. with ether and the insoluble product collected by filtration. Recrystallization from methanol gives colorless crystals (3.65 grams, melting point 150°-151.5°). An additional 4.1 grams of product are obtained from the filtrate.
Reaction SMILES: [C:1]([O:5][C:6]([O:8][C:9]1[CH:10]=[C:11]([CH:15]=[CH:16][C:17]=1[N+:18]([O-:20])=[O:19])[C:12](O)=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.C(OC(Cl)=O)C(C)C.[BH4-].[Na+]>C1COCC1.CO.CCOC(C)=O>[C:6](=[O:7])([O:8][C:9]1[CH:10]=[C:11]([CH2:12][OH:13])[CH:15]=[CH:16][C:17]=1[N+:18]([O-:20])=[O:19])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)Oc1cc(C(=O)O)ccc1[N+](=O)[O-]
Agent: CC(C)COC(=O)Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)Oc1cc(CO)ccc1[N+](=O)[O-]
Reaction time: 1 h
Yield: 63.1 %

Procedure:
A solution of 3-(tert-butoxycarbonyloxy)-4-nitrobenzoic acid (2.26 g, 8 mmol) and N-methylmorpholine (1.85 mL, 16.8 mmol) in THF (20 mL) at 0° C., was treated with isobutylchloroformate (1.09 mL, 8.4 mmol) and stirred for 1 h. The reaction mixture was added to a cooled (−78° C.) solution of NaBH4 (605 mg, 16 mmol) in MeOH (16 mL) and stirred at room temperature for 1 h. The reaction mixture was diluted with EtOAc (20 mL), washed with saturated NaHCO3 (10 mL) and 10% citric acid solution (10 mL), dried (MgSO4) and concentrated in vacuo to give tert-butyl (5-hydroxymethyl-2-nitrophenyl) carbonate (1.36 g, 86%) as a cream solid. This material was brominated directly using Method AB to give the title compound (961 mg, 58%) as a yellow oil: NMR δH (400 MHz, CDCl3) 8.09 (1H, d, J 8.4 Hz), 7.41 (1H, dd, J 8.4, 2.0 Hz), 7.34 (1H, d, J 2.0 Hz), 4.47 (2H, s) and 1.58 (9H, s).
Reaction SMILES: CS[C:3](SC)=[C:4]1[C:13](=[O:14])[C:12]([CH2:19][CH2:20][CH2:21][CH3:22])([CH2:15][CH2:16][CH2:17][CH3:18])[C:11]2[C:6](=[CH:7][C:8]([F:23])=[CH:9][CH:10]=2)[C:5]1=[O:24].CSC(SC)=C1C(=O)C(CCCC)(CCCC)C2C(=CC=CC=2)C1=O.[NH2:52][C:53]1[CH:58]=[CH:57][C:56]([I:59])=[CH:55][C:54]=1[S:60]([NH2:63])(=[O:62])=[O:61]>>[CH2:15]([C:12]1([CH2:19][CH2:20][CH2:21][CH3:22])[C:11]2[C:6](=[CH:7][C:8]([F:23])=[CH:9][CH:10]=2)[C:5]([OH:24])=[C:4]([C:3]2[NH:52][C:53]3[CH:58]=[CH:57][C:56]([I:59])=[CH:55][C:54]=3[S:60](=[O:62])(=[O:61])[N:63]=2)[C:13]1=[O:14])[CH2:16][CH2:17][CH3:18]
Reactant: Nc1ccc(I)cc1S(N)(=O)=O
Reactant: CCCCC1(CCCC)C(=O)C(=C(SC)SC)C(=O)c2cc(F)ccc21
Agent: CCCCC1(CCCC)C(=O)C(=C(SC)SC)C(=O)c2ccccc21
Product: CCCCC1(CCCC)C(=O)C(C2=NS(=O)(=O)c3cc(I)ccc3N2)=C(O)c2cc(F)ccc21

Procedure:
The title compound was prepared according to the procedure of Example 5D, substituting the compound of Example 18G for the compound of Example 5C, and substituting the compound of Example 20A for the compound of 2D. 1H NMR (300 MHz, CDCl3): δ 0.56 (m, 2 H) 0.77 (m, 6 H) 0.90 (m, 2 H) 1.18 (m, 4 H) 1.90 (m, 2 H) 2.30 (m, 2 H) 7.08 (dd, J=8.46, 4.41 Hz, 2 H) 7.43 (m, 2 H) 7.93 (m, 2 H) 8.28 (d, J=1.84 Hz, 1 H) 16.58 (s, 1 H).
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12].C(Cl)CCl.[CH3:18][NH2:19]>ClCCl.C(OCC)(=O)C>[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:19][CH3:18])=[O:7])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12]
Reactant: O=C(O)c1ccc(F)c([N+](=O)[O-])c1
Reactant: CN
Solvent: CCOC(C)=O
Solvent: ClCCl
Solvent: ClCCCl
Product: CNC(=O)c1ccc(F)c([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 91.6 %

Procedure:
4-Fluoro-3-nitrobenzoic acid (3.00 g, 16.2 mmoles) was dissolved in dichloromethane (100 mL) and cooled in an ice bath to 0–5° C. EDC (3.73 g, 19.5 mmoles) was added followed by dropwise addition of methylamine solution (8.1 mL, 16.2 mmoles, 2.0 M solution in THF). The mixture was allowed to slowly warm to room temperature and stirred for 2 h. The mixture was then diluted with ethyl acetate and washed successively with 1 M HCl, saturated aqueous NaHCO3 and brine. The organic extracts were dried over MgSO4, filtered and concentrated in vacuo to leave 4-fluoro-3-nitro-N-methylbenzamide as a yellow solid (2.94 g, 91%) which was used directly in the next step.
Reaction SMILES: Cl[C:2]1[C:7]2[CH:8]=[N:9][C:10]3[N:14]([CH2:15][CH3:16])[N:13]=[CH:12][C:11]=3[C:6]=2[N:5]2[N:17]=[C:18]([CH3:20])[CH:19]=[C:4]2[N:3]=1.[CH2:21]([NH:23][CH2:24][CH3:25])[CH3:22]>C(O)CCC>[CH2:21]([N:23]([CH2:24][CH3:25])[C:2]1[C:7]2[CH:8]=[N:9][C:10]3[N:14]([CH2:15][CH3:16])[N:13]=[CH:12][C:11]=3[C:6]=2[N:5]2[N:17]=[C:18]([CH3:20])[CH:19]=[C:4]2[N:3]=1)[CH3:22]
Reactant: CCn1ncc2c1ncc1c(Cl)nc3cc(C)nn3c12
Reactant: CCNCC
Solvent: CCCCO
Product: CCN(CC)c1nc2cc(C)nn2c2c1cnc1c2cnn1CC
Reaction time: 10 h
Yield: 82.5 %

Procedure:
8.6 g of 5-chloro-8-ethyl-2-methyl-8H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]pyrido[3,4-e]pyrimidine (0.03 mol) and 7.2 g of diethylamine are suspended in 50 ml of butyl alcohol and heated with stirring in an autoclave for 10 hours at 150°. After this time, the solvent is removed, the residue is treated with water and filtered off. Recrystallization from alcohol yields 8 g (83%) of N,N,8-triethyl-2-methyl-8H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]pyrido[3,4-e]pyrimidin-5-amine; m.p. 106°-108°.
Reaction SMILES: [CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:32][CH3:33])=[C:10]([CH2:19][NH:20][C:21]([C:23]3[N:28]=[C:27]([C:29](O)=[O:30])[CH:26]=[CH:25][CH:24]=3)=[O:22])[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2].[Br:34][C:35]1[CH:36]=[C:37]([CH2:41][NH2:42])[CH:38]=[CH:39][CH:40]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC>C(Cl)Cl>[Br:34][C:35]1[CH:36]=[C:37]([CH2:41][NH:42][C:29]([C:27]2[CH:26]=[CH:25][CH:24]=[C:23]([C:21]([NH:20][CH2:19][C:10]3[C:11]([NH:12][CH:13]4[CH2:18][CH2:17][O:16][CH2:15][CH2:14]4)=[C:6]4[CH:5]=[N:4][N:3]([CH2:1][CH3:2])[C:7]4=[N:8][C:9]=3[CH2:32][CH3:33])=[O:22])[N:28]=2)=[O:30])[CH:38]=[CH:39][CH:40]=1
Reactant: CCc1nc2c(cnn2CC)c(NC2CCOCC2)c1CNC(=O)c1cccc(C(=O)O)n1
Reactant: NCc1cccc(Br)c1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCc1nc2c(cnn2CC)c(NC2CCOCC2)c1CNC(=O)c1cccc(C(=O)NCc2cccc(Br)c2)n1
Temperature: 25 °C
Yield: 76.8 %

Procedure:
A mixture of 6-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-2-pyridinecarboxylic acid (600 mg, 1.326 mmol), 1-(3-bromophenyl)methanamine (247 mg, 1.326 mmol), HBTU (o-Benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate) (603 mg, 1.591 mmol) and Et3N (0.924 mL, 6.63 mmol) in DCM was stirred at room temperature over the weekend. The reaction was quenched with saturated NaHCO3 and extracted with DCM twice. The combined organic layers were washed with brine and then concentrated under vacuum to give a crude residue. It was then purified with flash chromatography eluting with 0 to 100% ethyl acetate in hexane (product came out at 100% ethyl acetate in hexane). The product fractions were combined to give N-[(3-bromophenyl)methyl]-N′-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-2,6-pyridinedicarboxamide (632 mg, 49.9%). LC-MS m/z 620 (M+H)+, 0.89 min (ret time).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:25])([CH:16]([C:18]1[CH:23]=[CH:22][N+:21]([O-])=[CH:20][CH:19]=1)[CH3:17])[CH2:10][N:11]1[CH:15]=[N:14][CH:13]=[N:12]1.[CH3:26][N:27](C)C(Cl)=O.C[Si](C#N)(C)C.CCOCC>ClCCl>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:25])([CH:16]([C:18]1[CH:23]=[CH:22][N:21]=[C:20]([C:26]#[N:27])[CH:19]=1)[CH3:17])[CH2:10][N:11]1[CH:15]=[N:14][CH:13]=[N:12]1
Reactant: CN(C)C(=O)Cl
Reactant: CC(c1cc[n+]([O-])cc1)C(O)(Cn1cncn1)c1ccc(F)cc1F
Agent: C[Si](C)(C)C#N
Solvent: CCOCC
Solvent: ClCCl
Product: CC(c1ccnc(C#N)c1)C(O)(Cn1cncn1)c1ccc(F)cc1F
Temperature: 25 °C
Reaction time: 60 h
Yield: 93.6 %

Procedure:
A mixture of the product of part (i) (20.0 g) and N,N-dimethylcarbamoyl chloride (6.80 g) in dichloromethane (250 ml) was stirred at room temperature for 2.5 days, giving a clear solution. Trimethylsilyl cyanide (6.35 g) was added and stirring was continued for a further 48 hours. Additional quantities of N,N-dimethylcarbamoyl chloride (1.30 g) and trimethylsilyl cyanide (1.30 g) were then added and the solution was stirred for a further 36 hours. The reaction was then washed successively with 10% potassium carbonate solution, brine and then dried (MgSO4). Evaporation of the solvent gave a solid which was stirred with ether and filtered to give the title compound, (19.2 g), m.p. 188°-189°.
Reaction SMILES: [C:1]12([C:11]3[C:12]([OH:30])=[CH:13][C:14]4[CH2:15][CH2:16][C@@H:17]5[C@@H:26]([C:27]=4[CH:28]=3)[CH2:25][CH2:24][C@@:22]3([CH3:23])[C@H:18]5[CH2:19][CH2:20][C:21]3=[O:29])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.C(O)C.[BH4-].[Na+]>CO>[C:1]12([C:11]3[C:12]([OH:30])=[CH:13][C:14]4[CH2:15][CH2:16][C@@H:17]5[C@@H:26]([C:27]=4[CH:28]=3)[CH2:25][CH2:24][C@@:22]3([CH3:23])[C@H:18]5[CH2:19][CH2:20][C@@H:21]3[OH:29])[CH2:2][CH:3]3[CH2:4][CH:5]([CH2:6][CH:7]([CH2:9]3)[CH2:8]1)[CH2:10]2
Reactant: C[C@]12CC[C@@H]3c4cc(C56CC7CC(CC(C7)C5)C6)c(O)cc4CC[C@H]3[C@@H]1CCC2=O
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: CO
Product: C[C@]12CC[C@@H]3c4cc(C56CC7CC(CC(C7)C5)C6)c(O)cc4CC[C@H]3[C@@H]1CC[C@@H]2O
Reaction time: 2 h
Yield: 59.5 %

Procedure:
2-(1-Adamantyl)-3-hydroxyestra-1,3,5(10)-trien-17-one (250 mg, 0.62 mmol) was added to cold ethanol (25 mL) and methanol (10 mL) to give a turbid solution. Sodium borohydride (NaBH4, 140 mg) was added in one portion and the reaction was continued with stirring for 2 hours. Solvents were removed on a rotary evaporator and crushed ice was added. On standing overnight, the initially formed oil became a solid. The solid was filtered and washed with water until the filtrate was pH neutral. The solid was dried in a vacuum oven at 50° C. to give the crude product (0.25 g), which was purified by flash chromatography (silica gel eluted with 18% ethyl acetate in hexanes). The pure product (200 mg, 79.6%) was recrystallized from chloroform and hexanes to obtain crystals (150 mg), and was then characterized as follows: (i) melting point=174-175° C.; (ii) 1H NMR (CDCl3, 300 MHZ) δ0.81 (s, 3H, C18—CH3), 2.76 (m, 2H, C6—CH2), 3.73 (t, 1H, C17—H), 4.78 (s, 1H, C3—OH), 6.38 (s, 1H, C4—H), 7.16 (s, 1H, C1—H); (iii) 13C NMR (CDCl3, 300 MHZ) δ10.95, 23.02, 26.33, 27.12, 28.77, 28.98 (3×C), 30.49, 36.54, 36.71, 37.01 (3×C), 38.89, 40.68 (3×C), 43.20, 44.22, 49.96, 81.99, 116.84, 124.06, 132.06, 133.83, 135.20, 152.36.
Reaction SMILES: [CH3:1][C:2]1([CH3:11])[C@H:7]2[CH2:8][C@@H:3]1[CH2:4][CH2:5][C@@H:6]2[CH2:9][OH:10].[H-].[Na+].[F:14][C:15]1[CH:22]=[CH:21][CH:20]=[C:19](F)[C:16]=1[C:17]#[N:18]>CN(C)C=O>[F:14][C:15]1[CH:22]=[CH:21][C:20]([O:10][CH2:9][C@H:6]2[CH2:5][CH2:4][C@H:3]3[CH2:8][C@@H:7]2[C:2]3([CH3:11])[CH3:1])=[CH:19][C:16]=1[C:17]#[N:18]
Reactant: N#Cc1c(F)cccc1F
Reactant: CC1(C)[C@H]2CC[C@H](CO)[C@@H]1C2
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC1(C)[C@H]2CC[C@H](COc3ccc(F)c(C#N)c3)[C@@H]1C2
Temperature: 25 °C
Reaction time: 1 h
Yield: 76.8 %

Procedure:
A solution of (1S,2S,5S)-(−)-myrtanol (1.0 g, 6.48 mmol) in dimethylformamide was added to a cooled (0° C.) slurry of sodium hydride (310 mg, 7.78 mmol) in dimethylformamide under nitrogen atmosphere. The reaction mixture was slowly warmed to room temperature, stirred for 1 hour. Again, cooled (0° C.), then a solution of 2,6-difluorobenzonitrile (1.08 g, 7.78 mmol) in dimethylfomamide was added, Stirred overnight at room temperature. The reaction mixture was poured on crushed-ice water, stirred. The reaction mixture was extracted with ethyl acetate, dried, filtered and concentrated. Purification by silica gel chromatography (1:1 hexanes in dichloromethane) yielded 1.36 g of 2-fluoro-5-((1S,2S,5S)-6,6-dimethylbicyclo[3.1.1]hept-2-ylmethoxy)benzonitrile.
Reaction SMILES: [N:1]1([C:6]2[N:10]=[C:9]([CH:11]=O)[N:8]([CH2:13][C:14]([F:17])([F:16])[F:15])[N:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl-].[CH3:19][C:20]1[CH:25]=[C:24]([CH3:26])[N:23]2[N:27]=[C:28]([CH2:30][P+](C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[N:29]=[C:22]2[N:21]=1.N1CCCN2CCCCCC=12>O1CCCC1>[CH3:19][C:20]1[CH:25]=[C:24]([CH3:26])[N:23]2[N:27]=[C:28]([CH:30]=[CH:11][C:9]3[N:8]([CH2:13][C:14]([F:17])([F:16])[F:15])[N:7]=[C:6]([N:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)[N:10]=3)[N:29]=[C:22]2[N:21]=1
Reactant: Cc1cc(C)n2nc(C[P+](c3ccccc3)(c3ccccc3)c3ccccc3)nc2n1
Reactant: O=Cc1nc(N2CCCC2)nn1CC(F)(F)F
Agent: [Cl-]
Solvent: C1CCC2=NCCCN2CC1
Solvent: C1CCOC1
Product: Cc1cc(C)n2nc(C=Cc3nc(N4CCCC4)nn3CC(F)(F)F)nc2n1
Temperature: 25 °C
Reaction time: 18 h
Yield: 23.4 %

Procedure:
A mixture of 3-(pyrrolidin-1-yl)-1-(2,2,2-trifluoroethyl)-1H-1,2,4-triazole-5-carbaldehyde (54 mg, 218 μmol, Eq: 1.00), ((5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)methyl)triphenylphosphonium chloride (99.8 mg, 218 μmol, Eq: 1.00) and 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine (82.8 mg, 544 μmol, Eq: 2.5) in tetrahydrofuran (3.36 ml) was stirred for 18 hours at 25° C. under argon atmosphere. Chromatography afforded 5,7-dimethyl-2-{2-[5-pyrrolidin-1-yl-2-(2,2,2-trifluoro-ethyl)-2H-[1,2,4]triazol-3-yl]-vinyl}-[1,2,4]triazolo[1,5-a]pyrimidine (20 mg/23.4%) as a light yellow viscous oil. MS: m/z=393.4 (M+H+).
Reaction SMILES: [Cl:1][C:2]1[C:3]([O:16]C)=[CH:4][C:5]2[CH:9]=[C:8]([CH2:10][CH2:11][CH2:12][CH3:13])[S:7][C:6]=2[C:14]=1[Cl:15].Cl.N1C=CC=CC=1>O>[CH2:10]([C:8]1[S:7][C:6]2[C:14]([Cl:15])=[C:2]([Cl:1])[C:3]([OH:16])=[CH:4][C:5]=2[CH:9]=1)[CH2:11][CH2:12][CH3:13]
Reactant: CCCCc1cc2cc(OC)c(Cl)c(Cl)c2s1
Agent: Cl
Solvent: c1ccncc1
Solvent: O
Product: CCCCc1cc2cc(O)c(Cl)c(Cl)c2s1
Reaction time: 5 h
Yield: 69.4 %

Procedure:
A mixture of 5.0 g of 6,7-dichloro-2-n-butyl-5-methoxybenzo[b]thiophene and 50 g of pyridine hydrochloride, under nitrogen, is heated with stirring in a 195° oil-bath for 5 hrs. After the reaction mixture has cooled, 1000 ml of water is added and the aqueous mixture is extracted with three 250-ml portions of ether. The organic layers are combined, washed with one 200-ml portion of 2N hydrochloric acid, two 250-ml portions of water, dried over anhydrous magnesium sulfate and filtered. The solvent is removed to give an oil. Crystallization with pentane and cooling gives 3.3 g of 2-n-butyl-6,7-dichloro-5-hydroxybenzo[b]thiophene, mp 35°.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:9]=[CH:10][N:11]([CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:27]([O:29]CC)=[O:28])[C:12]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[Cl:19].[OH-].[Na+]>>[C:27]([CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][N:11]1[C:12]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[Cl:19])=[C:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[Cl:1])[N:9]=[CH:10]1)([OH:29])=[O:28]
Reactant: CCOC(=O)CCCCCCCn1cnc(-c2ccccc2Cl)c1-c1ccccc1Cl
Agent: [Na+]
Agent: [OH-]
Product: O=C(O)CCCCCCCn1cnc(-c2ccccc2Cl)c1-c1ccccc1Cl
Yield: 66.6 %

Procedure:
4,5-Bis(2-chlorophenyl)-1-(7-ethoxycarbonylheptyl)-imidazole (0.4 g) was reacted with 2N sodium hydroxide in a method similar to Example 10. Work-up and chromatography on silica gel eluted with a dichloromethane:methanol gradient followed by recrystallisation from dichloro-methane and hexane gave 1-(7-carboxyheptyl)-4,5-bis-(2-chlorophenyI)imidazole (0.25 g, 67%) as a white solid, m.p. 145°-6°.
Reaction SMILES: [CH2:1]([O:3][C:4]([CH3:9])([CH3:8])[C:5](O)=[O:6])[CH3:2].C(Cl)CCl.C1C=CC2N(O)N=[N:20]C=2C=1.[NH4+].[OH-]>CC#N>[CH2:1]([O:3][C:4]([CH3:9])([CH3:8])[C:5]([NH2:20])=[O:6])[CH3:2]
Reactant: On1nnc2ccccc21
Reactant: CCOC(C)(C)C(=O)O
Agent: [NH4+]
Agent: [OH-]
Solvent: ClCCCl
Solvent: CC#N
Product: CCOC(C)(C)C(N)=O
Temperature: 25 °C
Reaction time: 2 h
Yield: 100.8 %

Procedure:
A solution of 2-ethoxy-2-methylpropanoic acid (1.1 g, 8.32 mmol) in MeCN (15 mL) was treated with EDC (1.596 g, 8.32 mmol) and HOBT (1.275 g, 8.32 mmol), stirred at RT for 2 h, treated with NH4OH (˜15M, 1.7 mL, ˜25.5 mmol) and stirred at RT overnight. The mixture was treated with satd. NaHCO3 and water, extracted with EtOAc (5×) and the combined organics were dried over MgSO4 and concentrated to dryness to afford 2-ethoxy-2-methylpropanamide (1.1 g, 101%) as a solid. 1H NMR (400 MHz, DMSO-d6): δ 7.03 (s, 2H), 3.31 (q, J=7.0 Hz, 2H), 1.21 (s, 6H), 1.10 (t, J=7.0 Hz, 3H).
Reaction SMILES: [CH2:1]([O:4][C:5]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[CH:7][C:6]=1[N+:13]([O-])=O)[CH:2]=[CH2:3].C1COCC1.[Cl-].[NH4+].Cl>C(O)C.[Fe].O>[CH2:1]([O:4][C:5]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[CH:7][C:6]=1[NH2:13])[CH:2]=[CH2:3]
Reactant: C=CCOc1cc(OC)ccc1[N+](=O)[O-]
Agent: [Fe]
Agent: Cl
Agent: [Cl-]
Solvent: CCO
Solvent: O
Solvent: C1CCOC1
Product: C=CCOc1cc(OC)ccc1N
Temperature: 80 °C
Yield: 60.9 %

Procedure:
2.09 g of 2-allyloxy-4-methoxynitrobenzene was dissolved in 20 ml of ethanol, 5 ml of THF, and 4 ml of water. Thereafter, 4.27 g of ammonium chloride and 2.23 g of iron were added to the reaction solution, and the obtained mixture was stirred while heating at 80° C. for 4 hours. Thereafter, 2 g of ammonium chloride, 1 g of iron, and 0.25 ml of 5 N HCl were added to the reaction solution, and the obtained mixture was further stirred while heating for approximately 2 hours. The reaction solution was stood to cool and then filtered through celite. A saturated sodium bicarbonate aqueous solution and ethyl acetate were added thereto, so as to separate an organic layer. The obtained organic layer was washed with a saturated sodium chloride solution and then dried over anhydrous magnesium sulfate. After removing the drying agent by filtration, the organic layer was concentrated under a reduced pressure, and the residue was then purified by NH silica gel column chromatography (hexane/ethyl acetate), so as to obtain 1.09 g of the subject compound.
Reaction SMILES: [BH4-].[Na+].[CH2:3]([CH:12]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=1)[N:13]1[CH:16]([O:17][C:18](=[O:20])[CH3:19])[CH:15]([C:21](=[O:23])[CH3:22])[C:14]1=[O:24])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][CH:5]=1>C(O)(C)C.O>[CH2:25]([CH:12]([CH2:3][C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][CH:5]=1)[N:13]1[CH:16]([O:17][C:18](=[O:20])[CH3:19])[CH:15]([CH:21]([OH:23])[CH3:22])[C:14]1=[O:24])[C:26]1[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=1
Reactant: COc1ccc(CC(Cc2ccc(OC)cc2)N2C(=O)C(C(C)=O)C2OC(C)=O)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CC(C)O
Solvent: O
Product: COc1ccc(CC(Cc2ccc(OC)cc2)N2C(=O)C(C(C)O)C2OC(C)=O)cc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A mixture of sodium borohydride (38 mg) and 1-(di-p-anisylmethyl)-3-acetyl-4-acetoxy-2-azetidinone (397 mg) in isopropanol (6 ml) was stirred for 0.5 hour at room temperature. The reaction mixture was diluted with water and extracted with ethyl acetate. The extract was washed with water, dried over anhydrous sodium sulfate and evaporated to give 1-(di-p-anisylmethyl)-3-(1-hydroxyethyl)-4-acetoxy-2-azetidinone (the product was a mixture of two stereoisomers (about 1:1) of hydroxyethyl group).
Reaction SMILES: [O:1]1[CH2:16][CH:2]1[CH2:3][O:4][C:5]1[CH:14]=[C:13]2[C:8]([CH:9]=[N:10][NH:11][C:12]2=[O:15])=[CH:7][CH:6]=1.[C:17]([NH2:21])([CH3:20])([CH3:19])[CH3:18]>>[C:17]([NH:21][CH2:16][CH:2]([OH:1])[CH2:3][O:4][C:5]1[CH:14]=[C:13]2[C:8]([CH:9]=[N:10][NH:11][C:12]2=[O:15])=[CH:7][CH:6]=1)([CH3:20])([CH3:19])[CH3:18]
Reactant: O=c1[nH]ncc2ccc(OCC3CO3)cc12
Reactant: CC(C)(C)N
Product: CC(C)(C)NCC(O)COc1ccc2cn[nH]c(=O)c2c1

Procedure:
7-(2,3-Epoxypropoxy)-1(2H)-phthalazinone was reacted with t-butylamine in a similar manner to that described in Example 1(iv) to give 7-(3-t-butylamino-2-hydroxypropoxy)-1(2H)-phthalazinone, the hydrochloride of which was recrystallised from ethanol and had m.p. 263°-264° (decomp).