Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:9][C@@H:10]3[N:16]([CH:17]=2)[C:15](=[O:18])[C:14]2[CH:19]=[C:20]([O:61][CH3:62])[C:21]([O:23][CH2:24][CH2:25][CH2:26][O:27][C:28]4[C:58]([O:59][CH3:60])=[CH:57][C:31]5[C:32](=[O:56])[N:33]6[CH:48]=[C:47](S(C(F)(F)F)(=O)=O)[CH2:46][C@H:34]6[C:35](=[O:45])[N:36]([CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42])[C:30]=5[CH:29]=4)=[CH:22][C:13]=2[N:12]([CH2:63][O:64][CH2:65][CH2:66][Si:67]([CH3:70])([CH3:69])[CH3:68])[C:11]3=[O:71])=[CH:4][CH:3]=1.[C:72]1(/[CH:78]=[CH:79]/B(O)O)[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=1.C(N(CC)CC)C>C(O)C.C1(C)C=CC=CC=1.O.ClCCl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:9][C@@H:10]3[N:16]([CH:17]=2)[C:15](=[O:18])[C:14]2[CH:19]=[C:20]([O:61][CH3:62])[C:21]([O:23][CH2:24][CH2:25][CH2:26][O:27][C:28]4[C:58]([O:59][CH3:60])=[CH:57][C:31]5[C:32](=[O:56])[N:33]6[CH:48]=[C:47]([CH:79]=[CH:78][C:72]7[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=7)[CH2:46][C@H:34]6[C:35](=[O:45])[N:36]([CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42])[C:30]=5[CH:29]=4)=[CH:22][C:13]=2[N:12]([CH2:63][O:64][CH2:65][CH2:66][Si:67]([CH3:70])([CH3:69])[CH3:68])[C:11]3=[O:71])=[CH:4][CH:3]=1
Reactant: OB(O)/C=C/c1ccccc1
Reactant: COc1cc2c(cc1OCCCOc1cc3c(cc1OC)C(=O)N1C=C(S(=O)(=O)C(F)(F)F)C[C@H]1C(=O)N3COCC[Si](C)(C)C)N(COCC[Si](C)(C)C)C(=O)[C@@H]1CC(c3ccc(N)cc3)=CN1C2=O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CCO
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: COc1cc2c(cc1OCCCOc1cc3c(cc1OC)C(=O)N1C=C(c4ccc(N)cc4)C[C@H]1C(=O)N3COCC[Si](C)(C)C)N(COCC[Si](C)(C)C)C(=O)[C@@H]1CC(C=Cc3ccccc3)=CN1C2=O

Procedure:
A mixture of triflate 9 (0.5 g), trans-2-phenylvinylboronic acid (0.091 g), triethylamine (0.38 g) and tetrakis(triphenylphosphine)palladium(0) (30 mL) in ethanol (3 mL), toluene (6 mL) and water (1 mL) was irradiated with microwaves for 8 minutes at 80° C. in a sealed microwave vial. The reaction mixture was diluted with dichloromethane washed with water and dried over magnesium sulphate. Excess solvent was removed by rotary evaporation under reduced pressure to afford the crude product which was used without further purification in the next reaction. Retention time 8.13 mins, ES+1014.13.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:6]([C:7]([OH:9])=O)[C:5]([OH:11])=[CH:4][CH:3]=1.[C:12]([N:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1)#[CH:13]>C(N(CC)CC)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:11][C:12]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)=[CH:13][C:7](=[O:9])[C:6]=2[CH:10]=1
Reactant: C#CN1CCOCC1
Reactant: O=C(O)c1cc(Cl)ccc1O
Solvent: CCN(CC)CC
Product: O=c1cc(N2CCOCC2)oc2ccc(Cl)cc12
Yield: 44.7 %

Procedure:
The methyl ester of 5-chlorosalicylic acid (2.00 g, 10.7 mmol) is mixed with ethynyl morpholine (neat, 1.00 g, 9.00 mmol) dropwise. The reaction is exothermic. When the mixture cools, triethylamine (TEA, 1 drop) is added and the liquid mixture immediately crystallized. The mixture is chromatographed (flash, SiO2, CH2Cl2 /EtOH, 95:5) to yield 6-chloro-2-(4-morpholinyl)-4H-1benzopyran-4-one (1.07 g, 45%). Mp 194°-5° C.; IR (mull) 2949, 2946, 2869, 2855, 1640, 1615, 1566, 1464, 1450, 1437, 1345, 1246, 1118, 822, 787 cm-1 ; 1H-NMR (CDCl3, 200 MHz, δ) 8.11 (d, J=2.5 Hz, 1H), 7.49 (dd, J=8.7, 2.5 Hz, 1 H), 7.23 (d, J=8.7 Hz, 1H), 5.49 (s, 1H), 3.85-3.82 (m, 4 H), 3.53-3.50 (m, 4 H); UV (EtOH) λ max (ε) 217 (31,360), 230 (24,900), 245 sh (12,100), 2908 h (11,170), 301 (15,810) , 315 (16,070); Mass Spectrum: ions at m/e (relative intensity) 267 (35), 265 (100), 210 (24) 209 (22), 208 (74), 207 (31), 180 (47), 154 (27), 126 (19), 52 (21); High resolution MS calc'd. for C13H12NO3Cl: 265.0506. Found: 265.0512. Anal. calc'd. for C13H14NO3Cl: C, 58.77; H, 4.55; N, 5.27; Cl, 13.34. Found: C, 58.52; H, 4.66; N, 5.11; Cl, 13.58.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[CH2:12][C:13]([OH:15])=O)[N:8]=[CH:7][CH:6]=[CH:5]2.[Br:16][C:17]1[C:18]([C:23]2[NH:27][N:26]=[CH:25][N:24]=2)=[C:19]([NH2:22])[S:20][CH:21]=1>>[Br:16][C:17]1[C:18]([C:23]2[NH:27][N:26]=[CH:25][N:24]=2)=[C:19]([NH:22][C:13](=[O:15])[CH2:12][C:11]2[CH:10]=[C:9]3[C:4]([CH:5]=[CH:6][CH:7]=[N:8]3)=[CH:3][C:2]=2[F:1])[S:20][CH:21]=1
Reactant: O=C(O)Cc1cc2ncccc2cc1F
Reactant: Nc1scc(Br)c1-c1ncn[nH]1
Product: O=C(Cc1cc2ncccc2cc1F)Nc1scc(Br)c1-c1ncn[nH]1

Procedure:
N-(4-Bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(6-fluoroquinolin-7-yl)acetamide was prepared from 2-(6-fluoroquinolin-7-yl)acetic acid (42 mg, 0.203 mmol) and 4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-amine (25 mg, 0.102 mmol) according to protocol A. Retention time (min)=2.338, method [7], MS (ESI) 432.0 (M+H); 1H NMR (300 MHz, CD3OD) δ 9.02 (d, J=4.2 Hz, 1H), 8.73 (d, J=8.0 Hz, 1H), 8.24 (d, J=7.2 Hz, 1H), 7.93 (s, 1H), 7.88 (d, J=10.0 Hz, 1H), 7.82 (dd, J=9.0, 4.2 Hz, 1H), 7.09 (s, 1H), 4.42 (s, 2H).
Reaction SMILES: Cl[C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]=1[C:13]1[O:17][C:16]([C:18]2[CH:23]=[CH:22][C:21]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)=[CH:20][C:19]=2[O:30][CH3:31])=[N:15][N:14]=1.Cl.[CH3:33][NH:34][CH3:35].C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.O>[CH3:31][O:30][C:19]1[CH:20]=[C:21]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[CH:22]=[CH:23][C:18]=1[C:16]1[O:17][C:13]([C:3]2[C:4]([C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)=[N:5][O:6][C:2]=2[N:34]([CH3:35])[CH3:33])=[N:14][N:15]=1
Reactant: CNC
Reactant: COc1cc(N2CCOCC2)ccc1-c1nnc(-c2c(-c3ccccc3)noc2Cl)o1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: O
Product: COc1cc(N2CCOCC2)ccc1-c1nnc(-c2c(-c3ccccc3)noc2N(C)C)o1
Temperature: 25 °C
Reaction time: 2 h
Yield: 77.7 %

Procedure:
To a suspension of 4-{4-[5-(5-chloro-3-phenyl-isoxazol-4-yl)-[1,3,4]oxadiazol-2yl]-3-methoxy-phenyl}-morpholine (100 mg, 0.23 mmol) in DMSO (1 mL) was added dimethylamine hydrochloride (93 mg, 1.14 mmol) and potassium carbonate (158 mg, 1.14 mmol). The reaction mixture was stirred for 2 h at ambient temperature. It was diluted with water (5 mL) and the resulting suspension was stirred for 15 min at this temperature. Filtration and washing with water (5 mL) and tert-butylmethylether (5 mL) afforded the title compound (80 mg, 78%) which was obtained as an off-white solid. MS: m/e=448.2 [M+H]+.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[C:7]([I:13])[CH:8]=[C:9]([Cl:12])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[NH3:14].CO>>[Cl:12][C:9]1[CH:10]=[C:11]2[C:6](=[C:7]([I:13])[CH:8]=1)[N:5]=[CH:4][N:3]=[C:2]2[NH2:14]
Reactant: Clc1cc(I)c2ncnc(Cl)c2c1
Reactant: N
Solvent: CO
Product: Nc1ncnc2c(I)cc(Cl)cc12
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To 4,6-dichloro-8-iodo-quinazoline (1.00 g, 3.08 mmol) was added 2.4 mL of 7N ammonia/methanol. The mixture was capped and shaken overnight at room temperature. The rxn was then concentrated via rotovap yielding product as a white solid. The product was purified by flash column (2.5-10% Methanol:Dichloromethane), yielding 450 mg of 6-chloro-8-iodo-quinazolin-4-amine 1H NMR (400 MHz, DMSO) δ 8.51-8.45 (s, 1H), 8.45-8.41 (d, J=2.0 Hz, 1H), 8.41-8.35 (d, J=1.9 Hz, 1H), 8.12-7.92 (bs, 2H). LCMS M/Z (M+H)=306.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:17])[CH2:9][S:10][CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:4][CH:3]=1.[CH3:18][C:19]([CH3:24])([CH2:22]O)[CH2:20][OH:21].C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:9][S:10][CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[O:21][CH2:20][C:19]([CH3:24])([CH3:22])[CH2:18][O:17]2)=[CH:4][CH:3]=1
Reactant: CCOC(=O)CSCC(=O)c1ccc(Cl)cc1
Reactant: CC(C)(CO)CO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: CCOC(=O)CSCC1(c2ccc(Cl)cc2)OCC(C)(C)CO1
Yield: 31.3 %

Procedure:
Ethyl {[2-(4-chlorophenyl)-2-oxoethyl]thio}acetate (8.15 g, 29.9 mmol) was dissolved in toluene (165 ml). 2,2-Dimethyl-1,3-propanediol (24.8 g, 238 mmol) and p-toluene sulfonic acid (300 mg) were added. The mixture was stirred at reflux in a Dean-Stark apparatus for 2.5 h and concentrated under reduced pressure. The crude product was dissolved in CH2Cl2. The mixture was washed with H2O (3×), brine, dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by flash-chromatography (Hexane:EtOAc 9:1) to give 3.36 g (31%) of the title compound as an yellow oil. MS (CI) M/z: 381.0 (M++Na, 100), 382.0 (15), 383.0 (30), 384 (5)
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][C:17]=1[F:23].C(O)C.[Cl:27][C:28]1[CH:29]=[C:30]([C:34]([N:36]=[C:37]=[S:38])=[O:35])[CH:31]=[CH:32][CH:33]=1>C1(C)C=CC=CC=1>[Cl:27][C:28]1[CH:29]=[C:30]([CH:31]=[CH:32][CH:33]=1)[C:34]([NH:36][C:37]([NH:20][C:19]1[CH:21]=[CH:22][C:16]([O:15][C:6]2[C:5]3[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=3)[N:9]=[CH:8][CH:7]=2)=[C:17]([F:23])[CH:18]=1)=[S:38])=[O:35]
Reactant: O=C(N=C=S)c1cccc(Cl)c1
Reactant: COc1cc2nccc(Oc3ccc(N)cc3F)c2cc1OC
Solvent: CCO
Solvent: Cc1ccccc1
Product: COc1cc2nccc(Oc3ccc(NC(=S)NC(=O)c4cccc(Cl)c4)cc3F)c2cc1OC
Temperature: 25 °C
Reaction time: 2 h
Yield: 90 %

Procedure:
4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 3-chloro-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (73 mg, yield 90%).
Reaction SMILES: [CH2:1]([O:8][C:9](=[O:14])[C@H:10]([CH2:12][OH:13])[NH2:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:15]([O:26][C@H:27]([CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[CH2:28][C:29](O)=[O:30])(=[O:25])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]CCC.C(Cl)CCl.CI>C(Cl)Cl>[CH2:1]([O:8][C:9](=[O:14])[C@H:10]([CH2:12][OH:13])[NH:11][C:29](=[O:30])[CH2:28][C@H:27]([O:26][C:15](=[O:25])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCCCCCCCCCC[C@H](CC(=O)O)OC(=O)CCCCCCCCC
Reactant: N[C@@H](CO)C(=O)OCc1ccccc1
Solvent: ClCCCl
Solvent: ClCCl
Solvent: CI
Product: CCCCCCCCCCC[C@H](CC(=O)N[C@@H](CO)C(=O)OCc1ccccc1)OC(=O)CCCCCC
Yield: 90.2 %

Procedure:
In the same manner as described in Example 2-(5), L-serine benzyl ester (250 mg, 1.08 mmol) was acylated with (R)-3-decanoyloxytetradecanoic acid (478 mg, 1.2 mmol) in the presence of EDC MeI (357 mg, 1.2 mmol) in CH2Cl2 to afford 0.52 g (84%) of N-[(R)-3-heptanoyloxytetradecanoyl]-L-serine benzyl ester: mp 52-53° C.; 1H NMR (CDCl3) δ 0.87 (t, 6 H, J=6.9 Hz), 1.1-1.7 (m, 34 H), 2.29 (t, 2 H, J=7.5 Hz), 2.49) (d, 2 H, J=5.8 Hz), 3.67 (s, 1 H), 3.97 (m, 2 H), 4.63 (m, 1 H), 5.19 (m, 3 H), 6.61 (d, 1 H, J=7.1 Hz), 7.35 (br s, 5 H).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([O:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([OH:28])=[C:23]([O:26][CH3:27])[CH:24]=3)[N:19]=[CH:18][CH:17]=2)[C:5]([C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)=[N:6][C:7]=1[CH3:8].C(=O)([O-])[O-].[K+].[K+].Br[CH2:36][CH2:37][OH:38]>CN(C)C=O>[CH3:1][C:2]1[CH:3]=[C:4]([O:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([O:28][CH2:36][CH2:37][OH:38])=[C:23]([O:26][CH3:27])[CH:24]=3)[N:19]=[CH:18][CH:17]=2)[C:5]([C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)=[N:6][C:7]=1[CH3:8]
Reactant: OCCBr
Reactant: COc1cc2c(Oc3cc(C)c(C)nc3-c3cccnc3)ccnc2cc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1cc2c(Oc3cc(C)c(C)nc3-c3cccnc3)ccnc2cc1OCCO
Temperature: 70 °C
Reaction time: 8 h
Yield: 79 %

Procedure:
4-(5,6-Dimethyl-[2,3′]bipyridin-3-yloxy)-6-methoxy-quinolin-7-ol (compound 345) (150 mg) was dissolved in N,N-dimethylformamide (4 ml) to prepare a solution. Potassium carbonate (167 mg) and 2-bromoethanol (0.09 ml) were added to the solution, and the mixture was stirred at 70° C. overnight. The solvent was removed by distillation under the reduced pressure, water was then added to the residue, and the mixture was extracted with chloroform. The chloroform layer was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by thin layer chromatography using chloroform-acetone to give the title compound (132 mg, yield 79%).
Reaction SMILES: [CH2:1]([NH:8][C:9]1[N:14]2[N:15]=[CH:16][C:17]([C:18](O)=[O:19])=[C:13]2[N:12]=[CH:11][C:10]=1[C:21]([N:23]1[CH2:28][CH2:27][CH:26]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([CH3:35])[CH:30]=2)[CH2:25][CH2:24]1)=[O:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:36][S:37]([NH2:40])(=[O:39])=[O:38]>>[CH2:1]([NH:8][C:9]1[N:14]2[N:15]=[CH:16][C:17]([C:18]([NH:40][S:37]([CH3:36])(=[O:39])=[O:38])=[O:19])=[C:13]2[N:12]=[CH:11][C:10]=1[C:21]([N:23]1[CH2:24][CH2:25][CH:26]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([CH3:35])[CH:30]=2)[CH2:27][CH2:28]1)=[O:22])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Cc1cccc(C2CCN(C(=O)c3cnc4c(C(=O)O)cnn4c3NCc3ccccc3)CC2)c1
Reactant: CS(N)(=O)=O
Product: Cc1cccc(C2CCN(C(=O)c3cnc4c(C(=O)NS(C)(=O)=O)cnn4c3NCc3ccccc3)CC2)c1
Yield: 38.5 %

Procedure:
In the same manner as in Example 1, step 6 and using 7-benzylamino-6-[4-(3-methylphenyl)piperidine-1-carbonyl]pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (0.09 g, 0.19 mmol) obtained in step 2 and methanesulfonamide (0.090 g, 0.950 mmol), the title compound (0.04 g, 38%) was obtained.
Reaction SMILES: [CH3:1][CH:2]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH:10]([CH3:12])[CH3:11])[C:5]=1[CH2:13][C:14]([C:16]1[C:17]([CH:30]([CH3:32])[CH3:31])=[C:18]([O:25][S:26](=[O:29])(=[O:28])[NH2:27])[C:19]([CH:22]([CH3:24])[CH3:23])=[CH:20][CH:21]=1)=[O:15])[CH3:3].S(=O)(=O)(O[C:36]1[C:41](C(C)C)=CC=C[C:37]=1C(C)C)N.S(=O)(=O)(OC1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)N>>[CH3:3][CH:2]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH:10]([CH3:11])[CH3:12])[C:5]=1[CH2:13][C:14]([C:16]1[C:17]([CH:30]([CH3:32])[CH3:31])=[C:18]([O:25][S:26](=[O:28])(=[O:29])[NH2:27])[C:19]([CH:22]([CH3:23])[CH3:24])=[CH:20][C:21]=1[CH:36]([CH3:41])[CH3:37])=[O:15])[CH3:1]
Reactant: CC(C)c1cccc(C(C)C)c1CC(=O)c1ccc(C(C)C)c(OS(N)(=O)=O)c1C(C)C
Reactant: CC(C)c1cccc(C(C)C)c1OS(N)(=O)=O
Agent: CC(C)c1cc(C(C)C)c(OS(N)(=O)=O)c(C(C)C)c1
Product: CC(C)c1cccc(C(C)C)c1CC(=O)c1c(C(C)C)cc(C(C)C)c(OS(N)(=O)=O)c1C(C)C

Procedure:
This compound was prepared in the same manner as for the title compound of Example 1, except that 2,6-diisoproplyphenyl sulfamate was replaced with 2,4,6-triisoproplyphenyl sulfamate, mp 152°-155° C.
Reaction SMILES: [C:1]1([C:7]2[CH:8]=[C:9]3[C:13](=[CH:14][CH:15]=2)[NH:12][CH:11]=[C:10]3[CH2:16][CH2:17][N:18]([CH3:20])[CH3:19])[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1>C(OCC)(=O)C.[Pd]>[CH:1]1([C:7]2[CH:8]=[C:9]3[C:13](=[CH:14][CH:15]=2)[NH:12][CH:11]=[C:10]3[CH2:16][CH2:17][N:18]([CH3:19])[CH3:20])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: CN(C)CCc1c[nH]c2ccc(C3=CCCCC3)cc12
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CN(C)CCc1c[nH]c2ccc(C3CCCCC3)cc12
Temperature: 25 °C
Reaction time: 5 h
Yield: 81.1 %

Procedure:
5-(Cyclohex-1-en-1-yl)-3-[2-(N,N-dimethylamino)ethyl]-1H-indole (Example 9a, 8.4 mg, 0.031 mmol) in ethyl acetate (2 mL) containing a spatula tip of Pd/C (10%) was stirred at room temperature under an atmosphere of hydrogen for 5 h. The crude product was filtered through celite using 10% 2M methanolic ammonia in dichloromethane to rinse. Evaporation of the solvent in vacuo yielded 5-cyclohexyl-3-[2-(N,N-dimethylamino)ethyl]-1H-indole (6.8 mg, 81%); HRMS-FAB+ for C18H26N2 :calculated MH+ :271.21744; found MH+ :271.21692.
Reaction SMILES: [NH:1]1[CH:5]=[C:4]([C:6]2[C:7]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[N:8][O:9][C:10]=2[CH3:11])[N:3]=[CH:2]1.[H-].[Na+].[CH2:20](Br)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(O)(=O)C>CN(C=O)C>[CH2:20]([N:1]1[CH:5]=[C:4]([C:6]2[C:7]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)=[N:8][O:9][C:10]=2[CH3:11])[N:3]=[CH:2]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: Cc1onc(-c2ccccc2)c1-c1c[nH]cn1
Reactant: BrCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CC(=O)O
Product: Cc1onc(-c2ccccc2)c1-c1cn(Cc2ccccc2)cn1
Reaction time: 2 h
Yield: 63.4 %

Procedure:
A solution of 4-(1H-imidazol-4-yl)-5-methyl-3-phenyl-isoxazole (100 mg, 0.44 mmol) in DMF (2 mL) was added over 10 min to a suspension of NaH (20 mg, 0.47 mmol) in DMF (1 mL) at room temperature and after 30 min benzyl bromide (83.5 mg, 0.49 mmol) was added. After 2 h at room temperature, the mixture was poured into aqueous acetic acid (10%) and extracted with ethyl acetate. The organic extracts were then washed with water and brine, and then dried over sodium sulphate and evaporated. Purification by chromatography (SiO2, heptane:ethyl acetate=1:1) afforded the title compound (88 mg, 63%) which was obtained as a colourless gum. MS: m/e=316.1 [M+H]+.
Reaction SMILES: [H-].[Na+].[CH2:3]1[O:5][CH:4]1[CH2:6][OH:7].[CH2:8](Br)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>CN(C=O)C.[I-].C([NH3+])CCC>[CH2:8]([O:7][CH2:6][CH:4]1[O:5][CH2:3]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: BrCc1ccccc1
Reactant: OCC1CO1
Agent: CCCC[NH3+]
Agent: [H-]
Agent: [I-]
Solvent: CN(C)C=O
Product: c1ccc(COCC2CO2)cc1
Temperature: 65 °C
Reaction time: 1 h
Yield: 70.9 %

Procedure:
Sodium hydride (60% oil dispersion, 23.6 g, 0.59 mol) was added in portions to a solution of glycidol (14) (40 g, 0.54 mol), benzyl bromide (101.5 g, 0.59 mol), and n-butylammonium iodide (0.24 g) in dry DMF (150 mL) at 25° C. (Step 12). The mixture was stirred for 1 hr at 65° C., poured over ice and then extracted with ether (2×75 mL). The combined ether extract was washed with water (3×75 mL) and dried over MgSO4. Distillation using a 12-in vigreux column afforded 62.9 g (71%) of glycidyl ##STR7## benzyl ether 15; bp 120°-122° C. (10 mm); 1H NMR (CDCl3) δ 2.6 (dd, 1H, OCHa), 2.8 (dd, 1H, OCHb), 3.2 (m, 1H, OCHc), 3.2 (dd, 1H, OCHd), 3.8 (dd, 1H, OCHe), 4.6 (dd, 2H, OCH2), 7.23 (s, 5H, phenyl).
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[O:9][CH:10]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:11]([OH:14])[CH2:12][N:13]=1.[C:21]1(/C(/C)=C/CNC(=O)C2C=CC=CC=2)C=CC=CC=1>>[CH3:21][C:10]1([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[O:9][C:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][CH:2]=2)=[N:13][CH2:12][CH:11]1[OH:14]
Reactant: OC1CN=C(c2ccccc2F)OC1c1ccccc1
Reactant: C/C(=C\CNC(=O)c1ccccc1)c1ccccc1
Product: CC1(c2ccccc2)OC(c2ccccc2)=NCC1O

Procedure:
(5RS, 6SR)-6-Methyl-2,6-diphenyl-5,6-dihydro-4H-1,3-oxazin-5-ol may be obtained in the following manner: working as in Example 22 for the preparation of (5RS, 6SR)-2-(2-fluorophenyl)-6-phenyl-5,6-dihydro-4H-1,3-oxazin-5-ol, but starting with (E)-N-(3-phenyl-2-buten-1-yl)benzamide (4.2 g), a 0.35 M solution (48 cc) of 3-chloroperbenzoic acid in dichloromethane and boron trifluoride etherate (2.6 g), and after purification of the oil obtained by chromatography on a column (height: 35 cm; diameter: 3 cm) of silica (0.2-0.063 mm), eluting with a mixture of cyclohexane and ethyl acetate (60:40 by volume) and collecting 30-cc fractions, fractions 9 to 17 being combined and concentrated to dryness under reduced pressure (4 kPa) at 45° C., followed by recrystallization of the residue obtained in isopropyl ether, (5RS, 6SR)-6-methyl-2,6-diphenyl-5,6-dihydro-4H-1,3-oxazin-5-ol (1.65 g, m.p. 130° C.) is obtained.
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:6]=[N:7][C:8]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)=[CH:9][CH:10]=1)=[O:4].[OH-].[Na+]>C1COCC1>[F:17][C:14]1[CH:15]=[CH:16][C:11]([C:8]2[N:7]=[CH:6][C:5]([C:3]([OH:4])=[O:2])=[CH:10][CH:9]=2)=[CH:12][CH:13]=1
Reactant: COC(=O)c1ccc(-c2ccc(F)cc2)nc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: O=C(O)c1ccc(-c2ccc(F)cc2)nc1
Temperature: 25 °C
Reaction time: 15 h
Yield: 37 %

Procedure:
Combine 6-bromopyridine-3-carboxylic acid methyl ester (1.03 g, 4.78 mmol), 4-fluorophenylboronic acid (1.88 g, 13.41 mmol), and cesium fluoride (2.55 g, 16.78 mmol) in DMF (25 mL) and water (4 mL) with stirring. Place the hetereogeneous reaction mixture, open to the air, in an oil bath maintained at 80° C. After 5 minutes of heating, add Pd(OAc)2 (150 mg, 0.67 mmol) in one portion. After 17 hours, cool the reaction to room temperature, dilute with ethyl acetate and filter through a short plug of celite with additional ethyl acetate. Wash the organics with water, dry over MgSO4, filter and evaporate. Purification by flash column chromatography yields 6-(4-fluorophenyl)pyridine-3-carboxylic acid methyl ester as a yellow solid. Dissolve the purified ester in THF (0.25M) and add an equal volume of 1M NaOH. Stir vigorously at room temperature for 15 hours. Upon completion, acidify the reaction with conc. HCL and collect the white precipitate by filtration. Drying under vacuum yields 385 mg (37%) of the title compound. MS (m/e): 218.1 (MH+)
Reaction SMILES: [O:1]=[O+][O-].[CH2:4]([CH:8]1[C:16]([CH3:18])([CH3:17])[C:15]2[C:10](=[CH:11][C:12]([CH3:19])=[CH:13][CH:14]=2)[C:9]1=[O:20])[CH:5]=CC>ClCCl.CO>[O:1]=[CH:5][CH2:4][CH:8]1[C:16]([CH3:18])([CH3:17])[C:15]2[C:10](=[CH:11][C:12]([CH3:19])=[CH:13][CH:14]=2)[C:9]1=[O:20]
Reactant: O=[O+][O-]
Reactant: CC=CCC1C(=O)c2cc(C)ccc2C1(C)C
Solvent: ClCCl
Solvent: CO
Product: Cc1ccc2c(c1)C(=O)C(CC=O)C2(C)C
Reaction time: 1 h
Yield: 94 %

Procedure:
An ozone stream (2.5 g ozone/hour) was conducted for 60 minutes while stirring through a solution, cooled to -70° of 12.7 g (RS)-2-(2-buten-1-yl)-3,3,6-trimethyl-1-indanone in 200 ml of anhydrous dichloromethane and 40 ml of anhydrous methanol. Subsequently, the solution was flushed with oxygen for 5 minutes and with argon for 10 minutes. After the addition of 6.12 ml of dimethyl sulfide, the mixture was stirred at room temperature for 18 hours. The reaction mixture was evaporated in a vacuum, the residue was treated with 150 ml of dichloromethane and, after the addition of 25 ml of water and 25 ml of trifluoroacetic acid, stirred at room temperature for 2.5 hours. The mixture was subsequently poured into 150 ml of water and neutralized by the spatula-wise addition of sodium hydrogen carbonate while stirring. An additional 100 ml of water were added. The phases were separated and the aqueous phase was extracted twice with 150 ml of dichloromethane each time. The combined organic phases were dried over magnesium sulfate and concentrated in a vacuum. 11.3 g (94%) of (RS)-2-(2-oxoethyl)-3,3,6-trimethyl-1-indanone were obtained as a light yellow oil.
Reaction SMILES: BrCBr.O.[F:5][C:6]1[CH:12]=[CH:11][CH:10]=[C:8]([OH:9])[C:7]=1[OH:13].[C:14]1(C(=CC=CC=1)O)O>[Cl-].C[N+](CCCCCCCC)(CCCCCCCC)CCCCCCCC.[OH-].[Na+].C(Cl)Cl>[F:5][C:6]1[CH:12]=[CH:11][CH:10]=[C:8]2[O:9][CH2:14][O:13][C:7]=12
Reactant: Oc1cccc(F)c1O
Reactant: Oc1ccccc1O
Agent: CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC
Agent: [Cl-]
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Solvent: BrCBr
Product: Fc1cccc2c1OCO2
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Aliquot 336 (methyltrioctylammonium chloride, 0.63 g, 1.6 mmol), dibromomethane (40.7 g, 234.2 mmol) and water (31 mL) were placed in a 500 mL 3-necked flask equipped with an addition funnel, condenser and a stir bar. The addition funnel was charged with a solution of 3-fluorocatechol (20.0 g, 160 mmol) in 5M sodium hydroxide (80 mL). The mixture in the flask was heated to reflux and the solution of the catechol was added dropwise with good stirring over 2 hours and the resulting dark mixture heated an additional 2 hours at reflux. After cooling to room temperature, the reaction was diluted with methylene chloride and the layers separated. The aqueous layer was extracted with methylene chloride and the combined organic layers dried (Na2SO4 with charcoal). Filtration and concentration to a constant weight on the rota-vap gave 1-fluoro-2,3-methylenedioxybenzene (14.6 g, 104.2 mmol) as a dark yellow oil: 1H NMR (CDCl3): 6.80 (m, 1H), 6.68 (m, 2H), 6.04 (s, 2H).