Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1([CH3:32])[CH2:11][CH:10]=[C:9]([C:12]2[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=2)[C:8]2[CH:7]=[C:6]([C:19]#[C:20][C:21]3[CH:31]=[CH:30][C:24]([C:25]([O:27]CC)=[O:26])=[CH:23][CH:22]=3)[CH:5]=[CH:4][C:3]1=2.CC1(C)CC=C(C2C=CC(O[Si](CC(C)C)(C)C)=CC=2)C2C=C(C#CC3C=CC(C(OCC)=O)=CC=3)C=CC1=2.O[Li].O>C1COCC1.O>[CH3:1][C:2]1([CH3:32])[CH2:11][CH:10]=[C:9]([C:12]2[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=2)[C:8]2[CH:7]=[C:6]([C:19]#[C:20][C:21]3[CH:22]=[CH:23][C:24]([C:25]([OH:27])=[O:26])=[CH:30][CH:31]=3)[CH:5]=[CH:4][C:3]1=2
Reactant: CCOC(=O)c1ccc(C#Cc2ccc3c(c2)C(c2ccc(C)cc2)=CCC3(C)C)cc1
Agent: CCOC(=O)c1ccc(C#Cc2ccc3c(c2)C(c2ccc(O[Si](C)(C)CC(C)C)cc2)=CCC3(C)C)cc1
Agent: [Li]O
Solvent: C1CCOC1
Solvent: O
Product: Cc1ccc(C2=CCC(C)(C)c3ccc(C#Cc4ccc(C(=O)O)cc4)cc32)cc1

Procedure:
A solution of 142.6 mg (0.339 mmol) of ethyl 4-[(5,6-dihydro-5,5-dimethyl-8-(4-methylphenyl)-2-naphthalenyl)ethynyl]benzoate (Compound 1) and 35.6 mg (0.848 mmol) of LiOH—H2O in 12 ml of THF/water (4:1, v/v), was stirred overnight at room temperature. The reaction mixture was extracted with hexanes, and the hexane fraction extracted with 5% aqueous NaOH. The aqueous layers .were combined and acidified with 1M HCl, and then extracted with EtOAc and Et2O. The combined organic layers were dried over Na2SO4 and concentrated in vacuo to give the title compound as a colorless solid. 1H NMR (d6-DMSO): δ7.91 (2H, d, J=8.4 Hz), 7.60 (2H, d, J=8.4 Hz), 7.47 (2H, s), 7.23 (4H, q, J=8.1 Hz), 7.01 (1H, s), 6.01 (1H, t, J=4.6 Hz), 2.35 (3H, s), 2.33 (2H, d, J=4.8 Hz), 1.30 (6H, s).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([F:13])[CH2:10][C@H:9]1[CH2:14][O:15][CH2:16][CH2:17][CH2:18]/[CH:19]=[CH:20]/[C:21]([O:23][CH3:24])=[O:22])=[O:7])([CH3:4])([CH3:3])[CH3:2]>CO.[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([F:13])[CH2:10][C@H:9]1[CH2:14][O:15][CH2:16][CH2:17][CH2:18][CH:19]=[CH:20][C:21]([O:23][CH3:24])=[O:22])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: COC(=O)/C=C/CCCOC[C@@H]1C[C@H](F)CN1C(=O)OC(C)(C)C
Agent: [Pd]
Solvent: CO
Product: COC(=O)C=CCCCOC[C@@H]1C[C@H](F)CN1C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 19 h
Yield: 101.1 %

Procedure:
Methyl (E)-6-((2S,4S)-1-(tert-butoxycarbonyl)-4-fluoro-2-pyrrolidinylmethoxy)-2-hexenoate (1.90 g, 5.50 mmol) and 5% palladium/carbon (1.0 g) were suspended in methanol (80 ml). The resulting suspension was subjected to catalytic hydrogenation under normal pressure for 19 hours under stirring at room temperature. The catalyst was filtered off and the filtrate was distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column (silica gel: 3 g), whereby from ethyl acetate eluate fractions, the title compound (1.92 g, 100%) was obtained as a colorless oil.
Reaction SMILES: CS[C:3](=[NH:8])[NH:4][N+:5]([O-:7])=[O:6].[NH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1[CH:15]=[C:16]([CH2:20][N:21]([CH3:23])[CH3:22])[CH:17]=[CH:18][CH:19]=1>C(O)C>[N+:5]([NH:4][C:3]([NH:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([CH2:20][N:21]([CH3:22])[CH3:23])[CH:15]=1)=[NH:8])([O-:7])=[O:6]
Reactant: CN(C)Cc1cccc(OCCCN)c1
Reactant: CSC(=N)N[N+](=O)[O-]
Solvent: CCO
Product: CN(C)Cc1cccc(OCCCNC(=N)N[N+](=O)[O-])c1

Procedure:
N-nitrocarbamimidothioic acid methylester (0.77 g) and 3-(3-aminopropoxy)-N,N-dimethylbenzenemethanamine (1.0 g) were heated in ethanol at 40° for 20 mins. The solution was cooled to precipitate the title compound which was filtered off and recrystallised from ethyl acetate as a white solid (0.44 g) m.p. 114°-115°. TLC silica; methanol:0.88 ammonia (80:1) Rf 0.48.
Reaction SMILES: [CH2:1]([OH:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:9][C:10]([CH3:19])([CH:17]=[CH2:18])[CH2:11][C:12](OCC)=[O:13].[O-]CC.[Na+]>C1(C)C=CC=CC=1>[CH3:9][C:10]([CH3:19])([CH:17]=[CH2:18])[CH2:11][C:12]([O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:13]
Reactant: OCc1ccccc1
Reactant: C=CC(C)(C)CC(=O)OCC
Agent: CC[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: C=CC(C)(C)CC(=O)OCc1ccccc1
Yield: 63.8 %

Procedure:
In the manner of Example I B, 810 mg of benzyl alcohol was reacted with 1122 mg of ethyl 3,3-dimethyl-4-pentenoate in the presence of 48 mg of sodium ethoxide in 30 ml of toluene to give 1.0 g (65% yield) of benzyl 3,3-dimethyl-4-pentenoate, b.p. 92°-98°/0.1 mm.
Reaction SMILES: O[C@H]1CCCC[C@@H]1N1C(=O)C2C(=C3C=CC=CC3=C(C[N:20]3[CH2:25][CH2:24][C:23]([C:28]4C=CC=CN=4)([C:26]#[N:27])[CH2:22][CH2:21]3)C=2)N=C1.N1C=CC=CC=1C1(C#N)CCNCC1>>[CH3:28][C:23]1([C:26]#[N:27])[CH2:24][CH2:25][NH:20][CH2:21][CH2:22]1
Reactant: N#CC1(c2ccccn2)CCN(Cc2cc3c(=O)n([C@H]4CCCC[C@@H]4O)cnc3c3ccccc23)CC1
Agent: N#CC1(c2ccccn2)CCNCC1
Product: CC1(C#N)CCNCC1

Procedure:
The title compound was prepared by the procedure described for the synthesis of 1-({3-[(1S,2S)-2-hydroxycyclohexyl]-4-oxo-3,4-dihydrobenzo[h]quinazolin-6-yl}methyl)-4-pyridin-2-ylpiperidine-4-carbonitrile in Example 2, substituting 4-methylpiperidine-4-carbonitrile for 4-pyridin-2-ylpiperidine-4-carbonitrile. The resultant solid gave proton NMR spectra consistent with theory and a mass ion (ES+) of 431.2438 for [M+H]+ [Calc'd for C26H31N4O2, [M+H]+=431.2444]: 1H NMR (400 MHz, CDCl3) δ 8.96-8.93 (m, 1H), 8.28-8.23 (m, 1H), 8.05 (s, 1H), 7.72-7.65 (m, 2H), 4.64 (br s, 1H), 4.04 (br s, 1H), 3.92 (s, 2H), 2.87 (br s, 2H), 2.56-2.53 (m, 1H), 2.45 (d, J=12.2 Hz, 2H), 2.29-2.26 (m, 1H), 2.09-1.86 (m, 5H), 1.64-1.41 (m, 5H), 1.36 (s, 3H).
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].Br[CH2:19][CH2:20][CH2:21][Cl:22]>CC(C)=O>[CH3:3][C:1]([C:5]1[CH:6]=[CH:7][C:8]([O:11][CH2:19][CH2:20][CH2:21][Cl:22])=[CH:9][CH:10]=1)([CH3:4])[CH3:2]
Reactant: ClCCCBr
Reactant: CC(C)(C)c1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CC(C)(C)c1ccc(OCCCCl)cc1
Temperature: 50 °C
Yield: 83.5 %

Procedure:
To a stirred solution of 4-tert-butylphenol (20.0 g, 0.16 mol) in acetone (500 mL) were added potassium carbonate (100 g, 0.72 mol) and 1-bromo-3-chloropropane (50.6 g, 0.33 mol). The reaction was heated to 50° C. for 18 hours. The reaction was filtered and the solvents evaporated to provide 30.3 g of 3-[4-(1,1-dimethylethyl)phenoxy]-1-chloropropane as a colorless oil; 200 MHz NMR δ 1.47 (s,9H), 2.36 (p, J=5.5Hz, 2H), 3.88 (t, J=5.5 Hz, 2H), 4.22 (t, J=5.5Hz, 2H), 7.0, 7.47 (ABq, J=9.6Hz, 4H).
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][CH:3]([C:6]2[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=2)[CH2:2]1.[C:12]1([C:18]2[O:22][N:21]=[CH:20][C:19]=2[C:23](O)=[O:24])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>O.CN1CCCC1=O>[C:12]1([C:18]2[O:22][N:21]=[CH:20][C:19]=2[C:23]([N:1]2[CH2:5][CH2:4][CH:3]([C:6]3[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=3)[CH2:2]2)=[O:24])[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: O=C(O)c1cnoc1-c1ccccc1
Reactant: c1cncc(C2CCNC2)c1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN1CCCC1=O
Solvent: O
Product: O=C(c1cnoc1-c1ccccc1)N1CCC(c2cccnc2)C1
Reaction time: 72 h
Yield: 50.9 %

Procedure:
To a 15 mL round-bottomed flask equipped with magnetic stirring was added 3-(pyrrolidin-3-yl)pyridine (250 mg, 1700 μmol, source: ASDI Inc.) and 4 mL of N-methylpyrrolidinone (NMP). 5-Phenylisoxazole-4-carboxylic acid (300 mg, 1600 μmol, source: CiVentiChem) was added followed by 1-hydroxybenzotriazole (250 mg, 1800 μmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (380 mg, 2000 μmol). Added 2 mL more NMP, and the reaction mixture was stirred at ambient temp. After 3 days, added 30 mL of water and extracted with EtOAc (3×15 mL). The organic layers were combined, washed with sat'd NaHCO3 and brine. The organic layers were then dried over MgSO4, filtered and concentrated in vacuo. The sample was absorbed onto silica gel and purified on a 40 g Isco Redi-sep® silica gel column that had been pre-equilibrated with CH2Cl2+2% MeOH. The product was eluted sample with CH2Cl2+2% (2M NH3 in MeOH). A viscous yellow oil was isolated as desired product (mass=260 mg). Mass Spec. m/z+ion=320.1.
Reaction SMILES: [I:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[NH:4][N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:19][CH2:20][OH:21]>CN(C)C=O>[NH2:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([CH2:19][CH2:20][OH:21])[N:3]=[C:2]([I:1])[C:10]=12
Reactant: OCCBr
Reactant: Nc1ncnc2[nH]nc(I)c12
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: Nc1ncnc2c1c(I)nn2CCO
Temperature: 25 °C
Reaction time: 72 h
Yield: 54.8 %

Procedure:
To 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (200 mg, 0.766 mmol) in N,N-Dimethylformamide (DMF) (5 mL) was added cesium carbonate (300 mg, 0.919 mmol) followed by 2-bromoethanol (0.057 mL, 0.805 mmol), and the reaction mixture was stirred over the weekend (3 days) at 80 C into a sealed vessel. The reaction was allowed to cool down to room temperature. The mixture was concentrated and treated with water (˜10 mL). The resulting aqueous mixture was sonicated, and then filtered. The solid in the filter was washed with water (2×10 mL) to afford 2-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethanol (128 mg) as a white solid after drying. LC/MS (ES) m/z=306.0 [M+H]+.
Reaction SMILES: C(OC([N:8]1[C:12]([CH2:13][CH2:14][C:15]23[CH2:24][CH:19]4[CH2:20][CH:21]([CH2:23][CH:17]([CH2:18]4)[CH2:16]2)[CH2:22]3)=[C:11]([NH:25][C:26]([NH:28][C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([O:37][CH2:38][C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)=[O:36])[CH:30]=2)=[O:27])[N:10]=[C:9]1[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=1[CH3:51])=O)(C)(C)C>FC(F)(F)C(O)=O>[CH2:38]([O:37][C:35](=[O:36])[C:31]1[CH:32]=[CH:33][CH:34]=[C:29]([NH:28][C:26]([NH:25][C:11]2[N:10]=[C:9]([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=3[CH3:51])[NH:8][C:12]=2[CH2:13][CH2:14][C:15]23[CH2:24][CH:19]4[CH2:20][CH:21]([CH2:23][CH:17]([CH2:18]4)[CH2:16]2)[CH2:22]3)=[O:27])[CH:30]=1)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1
Reactant: Cc1ccccc1-c1nc(NC(=O)Nc2cccc(C(=O)OCc3ccccc3)c2)c(CCC23CC4CC(CC(C4)C2)C3)n1C(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Product: Cc1ccccc1-c1nc(NC(=O)Nc2cccc(C(=O)OCc3ccccc3)c2)c(CCC23CC4CC(CC(C4)C2)C3)[nH]1
Temperature: 25 °C
Reaction time: 1 h
Yield: 94.9 %

Procedure:
The product of step d (237 mg, 0.34 mmol) was dissolved in trifluoroacetic acid (2 ml) and the solution was stirred at room temperature for 1 h. The trifluroracetic acid was removed in vacuo. The residue was partitioned between DCM and saturated aqueous sodium hydrogen carbonate. The organic layer was dried (MgSO4) and the solvent was evaporated to afford the product as a white solid (190 mg, 94%). 1H NMR (300 MHz, CDCl3) 10.84 (1H, br s), 8.96 (1H, br s), 8.08 (1H, s), 7.75 (1H, d), 7.52 (1H, d), 7.47-7.27 (1OH, m), 6.86 (1H, s), 5.36 (2H, s), 2.65 (3H, s), 2.57 (2H, m), 1.95 (3H, br s), 1.65 (6H, m), 1.51 (6H, s), 1.37 (2H, m).
Reaction SMILES: [N+:1]([C:4]1[CH:29]=[CH:28][C:7]([O:8][C:9]2[CH:10]=[C:11]([CH:25]=[CH:26][CH:27]=2)[C:12]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=2)=[O:13])=[CH:6][CH:5]=1)([O-])=O>[C].[Pd]>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([O:8][C:9]2[CH:10]=[C:11]([CH:25]=[CH:26][CH:27]=2)[C:12]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:22])([F:23])[F:24])[CH:16]=2)=[O:13])=[CH:28][CH:29]=1
Reactant: O=C(Nc1cccc(C(F)(F)F)c1)c1cccc(Oc2ccc([N+](=O)[O-])cc2)c1
Agent: [Pd]
Product: Nc1ccc(Oc2cccc(C(=O)Nc3cccc(C(F)(F)F)c3)c2)cc1
Yield: 65.8 %

Procedure:
Using 3-(4-nitrophenoxy)-N-[3-(trifluoromethyl)phenyl]benzamide (2.81 g, 10.0 mmol) and 10%-palladium carbon (1 g), and in the same manner as in Example A25(iv), the title compound (2.45 g, 69%) was obtained as a brown oil.
Reaction SMILES: [C:1]([BH3-])#[N:2].[Na+].[CH2:5]([O:12][C:13]1[CH:22]=[C:21]2[C:16]([CH2:17][CH2:18]N=[C:20]2[C:23]2([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[O:32][CH3:33])[CH2:25][CH2:24]2)=[CH:15][C:14]=1[O:34][CH3:35])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[OH-].[Na+].P([O-])([O-])O.[Na+].[Na+].C=O>CO.C(O)(=O)C>[CH2:5]([O:12][C:13]1[CH:22]=[C:21]2[C:16]([CH2:17][CH2:18][N:2]([CH3:1])[CH:20]2[C:23]2([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[O:32][CH3:33])[CH2:25][CH2:24]2)=[CH:15][C:14]=1[O:34][CH3:35])[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1
Reactant: [BH3-]C#N
Reactant: COc1cc2c(cc1OCc1ccccc1)C(C1(c3ccccc3OC)CC1)=NCC2
Agent: C=O
Agent: [Na+]
Agent: [O-]P([O-])O
Solvent: CO
Solvent: CC(=O)O
Product: COc1cc2c(cc1OCc1ccccc1)C(C1(c3ccccc3OC)CC1)N(C)CC2
Temperature: 0 °C

Procedure:
Sodium cyanoborohydride (7.4 g) was added to a stirred mixture of 7-benzyloxy-6-methoxy-1-[1-(2-methoxyphenyl) cyclopropyl]-3,4-dihydroisoquinoline (23.3 g) , acetic acid (125 ml) and methanol (65 ml) cooled by ice/water. After 16 hours at ambient temperature the mixture was added to sodium hydroxide (110 g) and ice. The product was extracted into ether and the organic layer dried over potassium carbonate and the solvent removed by evaporation to yield a solid. The solid (16.9 g) in industrial methylated spirits (1800 ml) was stirred for 3 days with 1M aqueous sodium hydrogen phosphite [340 ml prepared from phosphorous acid (27.9 g) and sodium hydrogen carbonate (28.5 g)] and 37-40% aqueous formaldehyde solution (180 ml). The solution was concentrated in vacuo to a volume of 200 ml and basified with potassium carbonate (40 g) in water (200 ml). The mixture was extracted with ether and the solvent removed from the extract to give a gum which was purified by azeotropic distillation with industrial methylated spirits then propan-2 -ol to yield 7-benzyloxy-6-methoxy-1-[1-(2-methoxyphenyl)cyclopropyl]-2-methyl-1,2,3,4-tetrahydroisoquinoline which was heated under reflux for 30 minutes with ethanol (200 ml) and concentrated hydrochloric acid (200 ml). The solvent was removed in vacuo to yield a solid which was dried by azeotropic distillation with propan-2-ol to produce a residue which was dissolved in acetonitrile (200 ml). Ethyl acetate (450 ml) was added, and the mixture boiled. The solution was decanted and evaporated in vacuo to give a residue which was triturated with cold ethyl acetate. The filtrate deposited further crystalline solid which was collected by filtration, washed in ethyl acetate and dried. The product yielded was 7-hydroxy-6-methoxy-1-[1-(2-methoxyphenyl)cyclopropyl]-2-methyl-1,2,3,4-tetrahydroisoquinoline hydrochloride, m.p. 118° C.
Reaction SMILES: I[C:2]([C:5]([O:8][C:9]([C:12]([S:15]([F:18])(=[O:17])=[O:16])([F:14])[F:13])([F:11])[F:10])([F:7])[F:6])([F:4])[F:3].[Si:19]([CH:26]=[CH2:27])([O:24][CH3:25])([O:22][CH3:23])[O:20][CH3:21].C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>N#N>[Si:19]([CH2:26][CH2:27][C:2]([C:5]([O:8][C:9]([C:12]([S:15]([F:18])(=[O:17])=[O:16])([F:14])[F:13])([F:11])[F:10])([F:7])[F:6])([F:4])[F:3])([O:24][CH3:25])([O:22][CH3:23])[O:20][CH3:21]
Reactant: O=S(=O)(F)C(F)(F)C(F)(F)OC(F)(F)C(F)(F)I
Reactant: C=C[Si](OC)(OC)OC
Agent: N#N
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Product: CO[Si](CCC(F)(F)C(F)(F)OC(F)(F)C(F)(F)S(=O)(=O)F)(OC)OC
Temperature: 95 °C
Reaction time: 0.67 h

Procedure:
Following the teachings of Beckerbauer et al, op.cit., U.S. Pat. No. 5,958,822, (CH3O)3SiCH2CH2CF2CF2OCF2CF2SO2F was prepared as follows. To a stirred mixture of 85 g (0.2 mol) of ICF2CF2OCF2CF2SO2F available from the Shanghai Institute of Organic Chemistry, Shanghai, China, and 32 g (0.215 mol) of (CH3O)3SiCH═CH2 (Aldrich Chemical Company) was added 0.5 g of benzoyl peroxide (Aldrich) at 90 to 95° C. in N2 and the resulting mixture was stirred at 95° C. for 40 minutes. An additional 0.5 g of benzoyl peroxide was added and the mixture was stirred for 4 hours more and then evacuated to remove excess starting materials. After the mixture was cooled to room temperature, 59 g of (C4H9)3SnH was slowly added and the mixture was stirred at room temperature overnight and distilled to give 60.9 g of liquid (CH3O)3SiCH2CH2CF2CF2OCF2CF2SO2F having a purity of greater than 99% and boiling point of 55° C./3 mm Hg. 19F NMR(CDCl3): +44.9 (s, 1F), −82.6 (m, 2F), −87.4 (m, 2F), −112.6 (s, 2F), −120.7 (t, J=15 Hz, 2F), 1HNMR: 3.60 (s, 9H), 2.10 (m, 2H), 0.70 (m, 2H).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:9]3=[C:10]([C:12]([CH2:15][CH2:16][N:17]4[CH2:22][CH2:21][N:20]([C:23]5[CH:28]=[C:27]([CH3:29])[CH:26]=[CH:25][N:24]=5)[CH2:19][CH2:18]4)=[C:13]([CH3:14])[N:8]3[CH2:7][CH2:6][CH2:5]2)[CH:11]=1.[C:30](Cl)(=[O:32])[CH3:31].C(N(CC)CC)C.[OH-].[Na+]>C1(C)C=CC=CC=1>[C:30]([O:1][C:2]1[CH:3]=[C:4]2[C:9]3=[C:10]([C:12]([CH2:15][CH2:16][N:17]4[CH2:22][CH2:21][N:20]([C:23]5[CH:28]=[C:27]([CH3:29])[CH:26]=[CH:25][N:24]=5)[CH2:19][CH2:18]4)=[C:13]([CH3:14])[N:8]3[CH2:7][CH2:6][CH2:5]2)[CH:11]=1)(=[O:32])[CH3:31]
Reactant: Cc1ccnc(N2CCN(CCc3c(C)n4c5c(cc(O)cc35)CCC4)CC2)c1
Reactant: CC(=O)Cl
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: CC(=O)Oc1cc2c3c(c1)c(CCN1CCN(c4cc(C)ccn4)CC1)c(C)n3CCC2
Yield: 73.9 %

Procedure:
2.2 g of 5,6-dihydro-2-methyl-8-hydroxy-1-{2-[4-(4-methylpyridin-2-yl)piperazin-1-yl]ethyl}-4H-pyrrolo[3,2,1-ij]quinoline (preparation see Example 6), 0.884 g of acetyl chloride and 0.78 ml of triethylamine were heated under reflux for 5 hours in 15 ml of toluene. To work up the reaction mixture it was added to 50 ml of 10% strength aqueous sodium hydroxide solution. The toluene phase was separated and washed with water until neutral and concentrated. 2 g of crude product were obtained, which was purified by chromatography on a small silica gel column using first dichloromethane and then dichloromethane/ethanol 98:2. 1.8 g of oily title compound were obtained. This was converted into its hydrochloride as described in Example 1H). 1.72 g of 8-acetoxy-5,6-dihydro-2-methyl-1-{2-[4-(4-methylpyridin-2-yl)piperazin-1-yl]ethyl}-4H-pyrrolo-[3,2,1-ij]quinoline 2 HCl 22.5 H2O having a melting point of 220° C. were obtained.
Reaction SMILES: Cl.[O:2]([NH2:4])[CH3:3].[C:5]([C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:18]=1[N:17]([CH3:19])[CH2:16][CH2:15][C:14]2=O)([CH3:8])([CH3:7])[CH3:6]>N1C=CC=CC=1>[CH3:3][O:2][N:4]=[C:14]1[C:13]2[C:18](=[C:9]([C:5]([CH3:7])([CH3:6])[CH3:8])[CH:10]=[CH:11][CH:12]=2)[N:17]([CH3:19])[CH2:16][CH2:15]1
Reactant: CON
Reactant: CN1CCC(=O)c2cccc(C(C)(C)C)c21
Agent: Cl
Solvent: c1ccncc1
Product: CON=C1CCN(C)c2c1cccc2C(C)(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Methoxylamine hydrochloride (0.86 g, 10.3 mmol) was added to a solution of Example 14D (2.04 g, 9.39 mmol) in pyridine (20 mL) and the mixture stirred overnight at ambient temperature. The mixture was concentrated under reduced pressure and ethyl acetate (200 mL) was added. The solution was washed twice with water (200 mL), once with brine, dried over anhydrous sodium sulfate, filtered, and concentrate under reduced pressure. The residue was chromatographed on silica gel eluting with 0-to-25% ethyl acetate in hexane to afford the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.41 (s, 9H), 2.46 (s, 3H), 2.80 (m, 2H), 3.07 (m, 2H), 3.93 (s, 3H), 7.11 (t, J=7.80 Hz, 1H), 7.35 (dd, J=7.97, 1.53 Hz, 1H), 7.62 (dd, J=7.63, 1.53 Hz, 1H). MS (DCI) m/z 247.14 (M+H)+.
Reaction SMILES: [N:1]1([C:7]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:8]=2[C:9]([NH2:18])=[N:10][C:11]([NH2:17])=[N:12]3)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[CH2:19]1[O:29][C:28]2[CH:27]=[CH:26][C:23]([CH2:24]Cl)=[CH:22][C:21]=2[O:20]1>>[O:29]1[C:28]2[CH:27]=[CH:26][C:23]([CH2:24][N:4]3[CH2:5][CH2:6][N:1]([C:7]4[CH:16]=[CH:15][CH:14]=[C:13]5[C:8]=4[C:9]([NH2:18])=[N:10][C:11]([NH2:17])=[N:12]5)[CH2:2][CH2:3]3)=[CH:22][C:21]=2[O:20][CH2:19]1
Reactant: ClCc1ccc2c(c1)OCO2
Reactant: Nc1nc(N)c2c(N3CCNCC3)cccc2n1
Product: Nc1nc(N)c2c(N3CCN(Cc4ccc5c(c4)OCO5)CC3)cccc2n1
Yield: 50 %

Procedure:
Title compound was prepared via Resin Method using 5-piperazin-1-yl-quinazoline-2,4-diamine (50 mg; 0.2 mmol) and 3,4-methylenedioxybenzyl chloride (63.1 mg; 0.37 mmol) to obtain 37.5 mg. (50% yield). 1H NMR (400 MHz, DMSO-d6) δ 9.34 (s, 1H), 7.92 (s, 1H), 7.51 (t, J=8.0 Hz, 1H), 7.04 (m, 2H), 6.85 (m, 3H), 6.65 (s, 2H), 6.0 (s, 2H), 3.47 (s, 2H), 2.99 (d, J=12.0 Hz, 2H), 2.85 (m, 4H), 2.24 (t, J=11.2 Hz, 2H).
Reaction SMILES: [C:1]([C:5]1[O:6][C:7]2[C:8](=[C:10]([C:14]([OH:16])=O)[CH:11]=[CH:12][CH:13]=2)[N:9]=1)([CH3:4])([CH3:3])[CH3:2].Cl.Cl.[NH2:19][C@H:20]1[CH:25]2[CH2:26][CH2:27][N:22]([CH2:23][CH2:24]2)[CH2:21]1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C=O)C.ClCCl>[N:22]12[CH2:27][CH2:26][CH:25]([CH2:24][CH2:23]1)[C@H:20]([NH:19][C:14]([C:10]1[CH:11]=[CH:12][CH:13]=[C:7]3[O:6][C:5]([C:1]([CH3:2])([CH3:3])[CH3:4])=[N:9][C:8]=13)=[O:16])[CH2:21]2
Reactant: N[C@@H]1CN2CCC1CC2
Reactant: CC(C)(C)c1nc2c(C(=O)O)cccc2o1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CC(C)(C)c1nc2c(C(=O)N[C@@H]3CN4CCC3CC4)cccc2o1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 64.9 %

Procedure:
A mixture of 2-tert-butylbenzoxazole-4-carboxylic acid (70 mg, 0.32 mmol), (S)-(−)-3-aminoquinuclidine dihydrochloride (64 mg, 0.32 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (123 mg, 0.64 mmol) and 1-hydroxybenzotriazole (86 mg, 0.64 mmol) in DMF (1.5 mL) was stirred at room temperature for 5 min, then triethylamine (0.17 mL, 1.28 mmol) was added. The resulting reaction mixture was stirred at room temperature for 12 h. The mixture was diluted with dichloromethane (20 mL), then washed with a saturated solution of sodium bicarbonate (10 mL). The aqueous layer was further extracted with dichloromethane (3×15 mL). The combined organics were dried (Na2SO4), filtered and concentrated. The crude material was purified by column chromatography (silica gel, 89:10:1 dichloromethane/methanol/concentrated ammonium hydroxide) to afford (S)—N-(1-azabicyclo[2.2.2]oct-3-yl)-2-tert-butylbenzoxazole-4-carboxamide (68 mg, 65%) as a colorless semi-solid: 1H NMR (500 MHz, CDCl3) δ 9.60 (d, J=7.5 Hz, 1H), 8.13 (dd, J=7.5, 1.0 Hz, 1H), 7.62 (dd, J=8.0, 2.0 Hz, 1H), 7.41 (t, J=8.0 Hz, 1H), 4.32-4.26 (m, 1H), 3.47 (ddd, J=11.5, 9.5, 2.0 Hz, 1H), 3.06-2.83 (m, 4H), 2.75 (dd, J=14.0, 4.5 Hz, 1H), 2.10-1.95 (m, 2H), 1.76-1.70 (m, 2H), 1.60-1.54 (m, 1H), 1.52 (s, 9H); MS (ESI+) m/z 328 (M+H); HPLC>99% (AUC), tR=11.84 min.
Reaction SMILES: [CH3:1][C:2]1([C:7]2[S:8][C:9]([CH2:12][N:13]3[N:17]=[C:16]([NH2:18])[CH:15]=[N:14]3)=[CH:10][N:11]=2)[O:6]CCO1.[C:19]1([C:25]2[O:29][CH:28]=[N:27][C:26]=2[C:30](O)=[O:31])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>>[C:2]([C:7]1[S:8][C:9]([CH2:12][N:13]2[N:17]=[C:16]([NH:18][C:30]([C:26]3[N:27]=[CH:28][O:29][C:25]=3[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)=[O:31])[CH:15]=[N:14]2)=[CH:10][N:11]=1)(=[O:6])[CH3:1]
Reactant: CC1(c2ncc(Cn3ncc(N)n3)s2)OCCO1
Reactant: O=C(O)c1ncoc1-c1ccccc1
Product: CC(=O)c1ncc(Cn2ncc(NC(=O)c3ncoc3-c3ccccc3)n2)s1

Procedure:
Following general procedure A followed by B, starting from 2-[2-(2-methyl-[1,3]dioxolan-2-yl)-thiazol-5-ylmethyl]-2H-[1,2,3]triazol-4-ylamine and 5-phenyl-oxazole-4-carboxylic acid.
Reaction SMILES: [O:1]=[C:2]([O:28][C:29]1[CH:37]=[CH:36][CH:35]=[C:34]2[C:30]=1[CH2:31][CH2:32][CH2:33]2)[CH:3]1[O:8][CH2:7][CH2:6][N:5](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH2:4]1.FC(F)(F)C(O)=O.N1CCOCC1.C(=O)([O-])O.[Na+]>O>[O:1]=[C:2]([O:28][C:29]1[CH:37]=[CH:36][CH:35]=[C:34]2[C:30]=1[CH2:31][CH2:32][CH2:33]2)[CH:3]1[O:8][CH2:7][CH2:6][NH:5][CH2:4]1
Reactant: O=C(Oc1cccc2c1CCC2)C1CN(C(c2ccccc2)(c2ccccc2)c2ccccc2)CCO1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: O
Solvent: C1COCCN1
Product: O=C(Oc1cccc2c1CCC2)C1CNCCO1
Reaction time: 0.25 h
Yield: 89.1 %

Procedure:
To 1 g. of 2-(1-oxo-4-indanyloxymethyl)-4-triphenylmethyl morpholine was added 10 ml. of trifluoroacetic acid under ice-cooling to dissolve the morpholine and 10 ml. of water was immediately added to the solution followed by stirring for 15 minutes at 5°-10° C. Then, after neutralizing the reaction mixture with sodium hydrogencarbonate, the product was extracted with chloroform. Then, the extract was washed with water, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The sticky residue formed was subjected to a silica gel column chromatography (column diameter 3 cm., height 7 cm,) and from the fraction recovered therefrom using a 98 : 2 mixture of chloroform and methanol as an eluting solution, 0.45 g. (yield 89.1%) of sticky 2-(1-oxo-4-indanyloxymethyl)morpholine was obtained.