Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH:10]([CH2:11][CH3:12])[CH2:9][CH:8](O)[N:7]1[C:14](=[O:16])[CH3:15])=[O:5])[CH3:2].C([SiH](CC)CC)C.FC(F)(F)C(O)=O>C(Cl)Cl>[C:14]([N:7]1[CH2:8][CH2:9][CH:10]([CH2:11][CH3:12])[C:6]1([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:4]([O:3][CH2:1][CH3:2])=[O:5])(=[O:16])[CH3:15]
Reactant: CCOC(=O)C1(C(=O)OCC)C(CC)CC(O)N1C(C)=O
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CCOC(=O)C1(C(=O)OCC)C(CC)CCN1C(C)=O
Temperature: 25 °C

Procedure:
To a solution of diethyl-1-acetyl-5-hydroxy-3-ethylpyrrolidine-2,2-dicarboxylate (287 g, 0.95 mol) and triethylsilane (228 mL, 1.43 mol) in CH2Cl2 (3 L) under argon was added trifluoroacetic acid (735 mL, 9.53 mol) dropwise with stirring while maintaining the internal temperature at 25° C. by means of an ice bath. After stirring for 3 h at 23° C., the solution was concentrated in vacuo, the residue diluted with CH2Cl2 (1.5 L), then treated with H2O (1 L) and solid Na2CO3 with vigorous stirring until the solution was basic. The organic layer was separated, dried (Na2SO4), filtered, then concentrated to give the title compound as a yellow oil which was used without further purification.
Reaction SMILES: C1(O[C:8](=[O:20])[NH:9][C:10]2[C:11]([O:18][CH3:19])=[N:12][C:13]([CH3:17])=[C:14]([CH3:16])[CH:15]=2)C=CC=CC=1.[C:21]1([N:35]2[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]2)[C:34]2[C:25](=[CH:26][C:27]3[C:32]([CH:33]=2)=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH:24]=[CH:23][CH:22]=1>>[CH3:16][C:14]1[CH:15]=[C:10]([NH:9][C:8]([N:38]2[CH2:37][CH2:36][N:35]([C:21]3[C:34]4[C:25](=[CH:26][C:27]5[C:32]([CH:33]=4)=[CH:31][CH:30]=[CH:29][CH:28]=5)[CH:24]=[CH:23][CH:22]=3)[CH2:40][CH2:39]2)=[O:20])[C:11]([O:18][CH3:19])=[N:12][C:13]=1[CH3:17]
Reactant: c1ccc2cc3c(N4CCNCC4)cccc3cc2c1
Reactant: COc1nc(C)c(C)cc1NC(=O)Oc1ccccc1
Product: COc1nc(C)c(C)cc1NC(=O)N1CCN(c2cccc3cc4ccccc4cc23)CC1
Yield: 62 %

Procedure:
Phenyl-N-(5,6-dimethyl-2-methoxypyridin-3-yl)carbamate and 1-(1-anthryl)piperazine were reacted by the same way with the example 1 to obtain the titled compound.
Reaction SMILES: I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[N:4]([CH:12]2[CH2:17][CH2:16][CH:15]([N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)[CH2:14][CH2:13]2)[N:3]=1.CC1(C)C(C)(C)OB([C:33]2[CH:38]=[CH:37][C:36]([NH:39][C:40]3[O:41][C:42]4[CH:48]=[CH:47][C:46]([CH2:49][CH3:50])=[CH:45][C:43]=4[N:44]=3)=[CH:35][CH:34]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.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>[NH2:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([C@H:12]3[CH2:17][CH2:16][C@@H:15]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)[CH2:14][CH2:13]3)[N:3]=[C:2]([C:33]3[CH:38]=[CH:37][C:36]([NH:39][C:40]4[O:41][C:42]5[CH:48]=[CH:47][C:46]([CH2:49][CH3:50])=[CH:45][C:43]=5[N:44]=4)=[CH:35][CH:34]=3)[C:10]=12
Reactant: CCc1ccc2oc(Nc3ccc(B4OC(C)(C)C(C)(C)O4)cc3)nc2c1
Reactant: CN1CCN(C2CCC(n3nc(I)c4c(N)ncnc43)CC2)CC1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Solvent: O
Product: CCc1ccc2oc(Nc3ccc(-c4nn([C@H]5CC[C@@H](N6CCN(C)CC6)CC5)c5ncnc(N)c45)cc3)nc2c1
Temperature: 80 °C

Procedure:
A mixture of 3-iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.06 g, 0.00014 mol), N2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-5-ethyl-1,3-benzoxazol-2-amine (0.062 g, 0.00017 mol), tetrakis(triphenylphosphine)palladium (0.011 g, 0.00001 mol) and sodium carbonate (0.037, 0.00035 mol) in ethylene glycol dimethyl ether (3 mL) and water (1 mL) was heated at 80° C. for 16 hours. The mixture was allowed to cool to ambient temperature, and the solvent was removed under the reduced pressure. The residue was partitioned between water and ethyl acetate. The aqueous layer was extracted with ethyl acetate (2×25 mL). The combined organic extracts were washed with water, saturated aqueous sodium bicarbonate solution, and brine, and dried over magnesium sulfate. The solvents were evaporated under the reduced pressure, and the residue was purified by flash column chromatography on silica using 2% aqueous ammonium hydroxide solution/5%-25% methanol/dichloromethane as a mobile phase. The solvent was removed under reduced pressure to give cis-N2-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenyl)-5-ethyl-1,3-benzoxazol-2-amine (0.065 g, 0.00012 mol). 1H NMR (DMSO-d6, 400 MHz) δ 11.25 (s, 1H), 8.65 (s, 1H), 8.37 (d, 2H), 8.09 (d, 2H), 7.84 (d, 1H), 7.76 (s, 1H), 7.42 (d, 1H), 5.22 (br, 1H), 3.13 (q, 2H), 2.52 (br, 7H), 2.69 (br, 4H), 2.64 (s, 3H), 2.49 (br, 2H), 2.11 (br, 2H), 2.01 (br, 2H), 1.63 (t, 3H). RP-HPLC (Delta Pak C18, 5 μm, 300 A, 15 cm; 5%-95% acetonitrile-0.1M ammonium acetate over 10 min, 1 mL/min) Rt 10.3 min. MS: MH+ 552
Reaction SMILES: [F:1][C:2]([F:6])([F:5])[CH2:3][NH2:4].[Cl:7][CH2:8][CH2:9][N:10]=[C:11]=[O:12]>C1COCC1>[Cl:7][CH2:8][CH2:9][NH:10][C:11]([NH:4][CH2:3][C:2]([F:6])([F:5])[F:1])=[O:12]
Reactant: O=C=NCCCl
Reactant: NCC(F)(F)F
Solvent: C1CCOC1
Product: O=C(NCCCl)NCC(F)(F)F
Yield: 93.8 %

Procedure:
A solution of 2,2,2-trifluoroethanamine (0.469 g, 4.74 mmol) and chloroethylisocyanate (0.50 g, 4.74 mmol) in THF (10 mL) was stirred at RT for 2 h, then concentrated to dryness. The residue was treated with DCM, concentrated to dryness and dried to afford 1-(2-chloroethyl)-3-(2,2,2-trifluoroethyl)urea (910 mg, 94%). 1H NMR (400 MHz, DMSO-d6): δ 6.67 (t, J=6.5 Hz, 1 H), 6.41 (m, 1 H), 3.80 (m, 2 H), 3.57 (t, J=6.2 Hz, 2 H), 3.32 (m, 2 H); MS (ESI) m/z: 205.0 (M+H+).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]1[C:18]2[C:13](=[C:14](Br)[CH:15]=[C:16]([O:19][CH3:20])[CH:17]=2)[CH2:12][NH:11][C:10]1=[O:22].[Cl:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.CCO.O.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>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]1[C:18]2[C:13](=[C:14]([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=3[Cl:23])[CH:15]=[C:16]([O:19][CH3:20])[CH:17]=2)[CH2:12][NH:11][C:10]1=[O:22]
Reactant: OB(O)c1ccccc1Cl
Reactant: COc1cc(Br)c2c(c1)N(c1c(Cl)cccc1Cl)C(=O)NC2
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: O
Solvent: CCO
Product: COc1cc(-c2ccccc2Cl)c2c(c1)N(c1c(Cl)cccc1Cl)C(=O)NC2
Temperature: 25 °C

Procedure:
Palladium tetrakis triphenylphosine (140 mg, 0.12 mmol) was added to 1-(2,6-dichlorophenyl)-5-bromo-7-methoxy-3,4-dihydro-2(1H)-quinazolinone (1.02 g, 2.54 mmol) (INTERMEDIATE 23), 2-chlorophenyl boronic acid (642 mg, 4.11 mmol) and sodium carbonate (436 mg, 4.11 mmol) in 150 mL toluene, 40 mL EtOH and 40 mL water under an argon atmosphere. After refluxing 3 h the solution was cooled to RT and partition between water and EtOAc. The organic phase was washed with water′(1×) and brine (1×) and dried over MgSO4. The solution was filtered and concentrated. The residue was absorbed on SiO2 and purified by silica gel bromatography using 3 to 5% acetone in DCM to give 1-(2,6-dichlorophenyl)-5-(2-chlorophenyl)-7-methoxy-3,4-dihydro-2(1H)-quinazolinone as a white solid. 1H NMR(CDCl3, 500 MHz): δ 3.68 (s, 3H), 4.17 (d, 1H, J=14.0 Hz), 4.36 (d, 1H, J=14.0 Hz), 5.28 (s, 1H), 5.74 (d, 1H, J=2.3 Hz), 6.43 (d, 1H, J=2.5 Hz), 7.29-7.37 (m, 4H), 7.47-7.51 (m, 3H). MS(ES) 433 (M+H); LC 1: 3.12 min.
Reaction SMILES: [CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=O)[C:10]([OH:12])=[O:11])[N:8]=1)=[O:2].[NH2:14][O:15][CH2:16][C:17]([O:19][CH:20]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18].C(OCC)(=O)C>O.N1C=CC=CC=1.O1CCCC1>[CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:14][O:15][CH2:16][C:17]([O:19][CH:20]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])[C:10]([OH:12])=[O:11])[N:8]=1)=[O:2]
Reactant: NOCC(=O)OC(c1ccccc1)c1ccccc1
Reactant: O=CNc1nc(C(=O)C(=O)O)cs1
Solvent: C1CCOC1
Solvent: O
Solvent: CCOC(C)=O
Product: O=CNc1nc(C(=NOCC(=O)OC(c2ccccc2)c2ccccc2)C(=O)O)cs1
Temperature: 25 °C
Reaction time: 3 h
Yield: 98.7 %

Procedure:
To a suspension of (2-formamidothiazol-4-yl)glyoxylic acid (6.0 g) in water (60 ml) and pyridine (6 ml) was added a solution of benzhydryl 2-aminooxyacetate (9.0 g) in tetrahydrofuran (40 ml). The reaction mixture was stirred at ambient temperature for 3 hours. To the resultant solution was added ethyl acetate (200 ml). The separated organic layer was washed with 5% hydrochloric acid (100 ml), a saturated aqueous sodium bicarbonate and a saturated aqueous sodium chloride, and then dried over magnesium sulfate. The solvent was distilled off to give 2-(2-formamidothiazol-4-yl)-2-benzhydryloxycarbonylmethoxyiminoacetic acid (syn isomer) (13.0 g), mp 143°-151° C.
Reaction SMILES: O.[NH2:2][C:3]1[NH:7][N:6]=[N:5][N:4]=1.[CH2:8]([O:10][CH:11](OCC)OCC)[CH3:9]>>[CH2:8]([O:10][CH:11]=[N:2][C:3]1[NH:7][N:6]=[N:5][N:4]=1)[CH3:9]
Reactant: Nc1nnn[nH]1
Reactant: CCOC(OCC)OCC
Solvent: O
Product: CCOC=Nc1nnn[nH]1
Temperature: 100 °C
Reaction time: 4 h

Procedure:
A mixture of 25 g of 5-aminotetrazole monohydrate and 356 g of triethoxymethane was heated under nitrogen with stirring at 100° C. for 4 hours during which time a distillate was collected. Then, 30 ml of cyclohexane was added and the mixture was cooled first to room temperature and then briefly with an ice-water bath. The white crystals which formed were separated by filtration and vacuum oven dried to give 5-(ethoxymethyleneamino)tetrazole.
Reaction SMILES: C(O[C@@H:5]1[O:22][C@H:21]([CH2:23][O:24][C:25](=[O:27])[CH3:26])[C@@H:16]([O:17][C:18](=[O:20])[CH3:19])[C@H:11]([O:12][C:13](=[O:15])[CH3:14])[C@H:6]1[O:7][C:8](=[O:10])[CH3:9])(=O)C.[CH3:28][C:29]1[CH:34]=[CH:33][C:32]([C:35]([CH3:38])([CH3:37])[CH3:36])=[CH:31][C:30]=1[SH:39].B(F)(F)F.CCOCC>C(Cl)Cl>[C:8]([O:7][C@@H:6]1[C@@H:11]([O:12][C:13](=[O:15])[CH3:14])[C@H:16]([O:17][C:18](=[O:20])[CH3:19])[C@@H:21]([CH2:23][O:24][C:25](=[O:27])[CH3:26])[O:22][C@H:5]1[S:39][C:30]1[CH:31]=[C:32]([C:35]([CH3:37])([CH3:36])[CH3:38])[CH:33]=[CH:34][C:29]=1[CH3:28])(=[O:10])[CH3:9]
Reactant: CC(=O)OC[C@H]1O[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: Cc1ccc(C(C)(C)C)cc1S
Agent: FB(F)F
Solvent: ClCCl
Solvent: CCOCC
Product: CC(=O)OC[C@H]1O[C@@H](Sc2cc(C(C)(C)C)ccc2C)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Yield: 84.9 %

Procedure:
1,2,3,4,6-Penta-O-acetyl-β-D-glucopyranose 8 (30 g, 77 mmol) was dissolved in anhydrous DCM (34 mL). 2-Methyl-5-tert-butyl thiophenol (17 mL, 92 mmol, 1.2 eq) were added under stirring. BF3.OEt2 (13.6 mL, 108 mmol, 1.4 eq) was added dropwise and the resulting yellow solution was stirred over night. After completion the solution was diluted with DCM and extracted with saturated aqueous NaHCO3 and H2O, and the organic layer was dried over MgSO4. The solvent was evaporated in vacuo and the residue was dried in high vacuum. The resulting yellow solid was purified by column chromatography on silica gel (cyclohexane/ethyl acetate) to afford 9 (33.4 g, 65.4 mmol, 85%). [α]D20=−8.0° (c=1.0, CHCl3); IR (CHCl3): 2961, 1747, 1366, 1211, 1034, 912 cm−1; 1H-NMR (400 MHz, CDCl3) δ 7.52 (1H, d, J 2.0, Ar—H), 7.25-7.10 (2H, m, Ar—H), 5.19 (1H, dd, J1J2 9.4, 1-H), 5.10-4.98 (2H, m, 4-H, 2-H), 4.64 (1H, d, J 10.6, 1-H), 4.23 (1H, dd, J1 12.2, J2 5.0, 6-Ha), 4.10 (1H, dd, J112.2, J2 1.9, 6-Hb), 3.71-3.63 (1H, m, 5-H), 2.34 (3H, s, CH3), 2.07-2.03 (6H, m, OAc), 2.00-1.96 (6H, m, OAc), 1.29 (9H, s, tBu); 13C-NMR (100 MHz, CDCl3) δ 170.8, 170.3, 169.5, 169.4 (C═O OAc), 149.8, 137.51, 131.47, 130.53, 130.2, 125.8, 87.0 (C-1), 75.9 (C-5), 74.2 (C-3), 70.3 (C-3), 68.3 (C-4), 62.4 (C-6), 31.4 (tBu), 20.89, 20.88, 20.74, 20.70 (OAc), 20.5 (CH3); HRMS (ESI): Calcd for C25H34O9S [M+Na]+ 533.1816. found 533.1832.
Reaction SMILES: N1N(C2C=CC(C(F)(F)F)=CC=2C(O)=O)N=CC=1.N1(C2C=CC(C(F)(F)F)=CC=2C(O)=O)C=CN=N1.[N:37]1[NH:38][N:39]=[CH:40][CH:41]=1.Br[C:43]1[C:51]([F:52])=[CH:50][C:49]([F:53])=[CH:48][C:44]=1[C:45]([OH:47])=[O:46]>O1CCOCC1.O>[F:52][C:51]1[C:43]([N:38]2[N:39]=[CH:40][CH:41]=[N:37]2)=[C:44]([CH:48]=[C:49]([F:53])[CH:50]=1)[C:45]([OH:47])=[O:46]
Reactant: c1cn[nH]n1
Reactant: O=C(O)c1cc(F)cc(F)c1Br
Agent: O=C(O)c1cc(C(F)(F)F)ccc1-n1ccnn1
Agent: O=C(O)c1cc(C(F)(F)F)ccc1-n1nccn1
Solvent: O
Solvent: C1COCCO1
Product: O=C(O)c1cc(F)cc(F)c1-n1nccn1

Procedure:
Prepared according to the procedure for 2-(2H-1,2,3-triazol-2-yl)-5-(trifluoromethyl)benzoic acid (Intermediate 37a) and 2-(1H-1,2,3-triazol-1-yl)-5-(trifluoromethyl)benzoic acid (Intermediate 37b) from 2H-1,2,3-triazole (CAS number 288-36-8; 1.0 g, 10.86 mmol) and 2-bromo-3,5-difluorobenzoic acid (CAS number 651027-01-9; 1.27 g, 5.43 mmol) in 1,4-dioxane (5 ml) and water (1 ml). The crude solid was purified by using column chromatography (silica, 0-3% methanol/DCM) to afford 3,5-difluoro-2-(2H-1,2,3-triazol-2-yl)benzoic acid (Intermediate 40a). The mixed fractions were further purified by column chromatography (silica, 0-3% methanol/DCM) followed by reverse phase preparative HPLC (eluted with acetonitrile/water containing 0.1% formic acid) to afford 3,5-difluoro-2-(1H-1,2,3-triazol-1-yl)benzoic acid (Intermediate 40b).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([C:12]([O:14][CH3:15])=[O:13])[CH:5]=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].C1(C)C=CC(S(O[CH2:26][C@H:27]2[CH2:31][O:30][C:29]([CH3:33])([CH3:32])[O:28]2)(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH3:32][C:29]1([CH3:33])[O:28][C@@H:27]([CH2:26][O:1][C:2]2[CH:11]=[C:6]([C:7]([O:9][CH3:10])=[O:8])[CH:5]=[C:4]([CH:3]=2)[C:12]([O:14][CH3:15])=[O:13])[CH2:31][O:30]1
Reactant: Cc1ccc(S(=O)(=O)OC[C@H]2COC(C)(C)O2)cc1
Reactant: COC(=O)c1cc(O)cc(C(=O)OC)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)c1cc(OC[C@H]2COC(C)(C)O2)cc(C(=O)OC)c1
Temperature: 0 °C

Procedure:
2.1 g of dimethyl 5-hydroxy-isophthalate and 2.9 g of (R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl toluene-4-sulfonate were stirred at reflux for 3 hours in 120 ml of dimethylformamide with the addition of 6.9 g of potassium carbonate. The reaction mixture was poured on to ice-water, extracted with methylene chloride, the combined methylene chloride phases were washed with water, dried over magnesium sulfate, filtered and evaporated. There was obtained dimethyl (S)-5-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-isophthalate, MS: m/z 324 ([M]+).
Reaction SMILES: [CH3:1][N:2]([CH:9]=O)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.P(Cl)(Cl)(Cl)=O.[NH2:16][C:17]1[S:18][CH:19]=[CH:20][N:21]=1>C1(C)C=CC=CC=1.NC1SC=CN=1>[S:18]1[CH:19]=[CH:20][N:21]=[C:17]1[N:16]=[CH:9][N:2]([CH3:1])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: CN(C=O)c1ccccc1
Reactant: Nc1nccs1
Solvent: Cc1ccccc1
Solvent: O=P(Cl)(Cl)Cl
Product: CN(C=Nc1nccs1)c1ccccc1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 94.2 %

Procedure:
To a stirred suspension of N-methylformanilide (67.6 g; 0.50 mole), toluene (25 g) and 2-aminothiazole (2.0 g; 0.02 mole) was added phosphorus oxychloride (45.8 mL; 0.50 mole) over 15 minutes. The temperature was maintained below 45° C. during this addition. Stirring was continued for 10 minutes, after which time a hot solution of 2-aminothiazole (48.0 g; 0.48 mole) in toluene (250 g) was added at 60°-65° C. over 45 minutes. The reaction was allowed to cool to room temperature with stirring and was quenched by dropwise addition into a mixture of 30% sodium hydroxide (325 g) and ice (300 g). The organic phase was washed with a mixture of water (100 g), sodium chloride (10 g), and sodium bicarbonate (7.5 g), followed by a saturated solution of sodium chloride (125 g); the resultant organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated to yield 98.3 g of crude product. Vacuum distillation gave pure 1 (60.0 g; 55.3%) as a yellow oil: bp 177° C. @ 0.5 mm Hg. 1H-NMR (CDCl3) 8.72 (s, 1H), 7.4-6.9 (m, 7H), 3.50 (S, 3H); IR(neat) 3075, 2950, 1615, 1580, 1490, 1345, 1310, 1120; MS (m/e) 217 (M+, base).
Reaction SMILES: Cl.[NH2:2][C:3]1[CH:12]=[C:11]2[CH:6]([CH2:7][CH2:8][N:9]([CH3:14])[CH:10]2[CH3:13])[CH2:5][CH:4]=1.[Br:15][C:16]1[CH:17]=[C:18]([CH:22]=[CH:23][C:24]=1[CH2:25][CH3:26])[C:19](Cl)=[O:20].C(N(CC)CC)C>ClCCl>[CH3:13][CH:10]1[C:11]2[C:6](=[CH:5][CH:4]=[C:3]([NH:2][C:19](=[O:20])[C:18]3[CH:22]=[CH:23][C:24]([CH2:25][CH3:26])=[C:16]([Br:15])[CH:17]=3)[CH:12]=2)[CH2:7][CH2:8][N:9]1[CH3:14]
Reactant: CC1C2=CC(N)=CCC2CCN1C
Reactant: CCc1ccc(C(=O)Cl)cc1Br
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCc1ccc(C(=O)Nc2ccc3c(c2)C(C)N(C)CC3)cc1Br
Temperature: 25 °C
Reaction time: 18 h

Procedure:
(±) 7-Amino-1,2-dimethyl-tetrahydroisoquinoline mono hydrochloride (0.106 g, 0.50 mmol) in dichloromethane (10 ml) was sequentially treated with 3-bromo-4-ethylbenzoyl chloride (0.124 g, 0.50 mmol) and triethylamine (0.3 ml, 2.2 mmol). The mixture was stirred at ambient temperature for 18 h. Evaporation in vacuo gave an oily residue which was purified by chromatography through silica gel eluting with (0.5% conc. ammonia: 4.5% methanol: 95% dichloromethane). The title compound was obtained as an off-white foam (0.149 g, 77%).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH2:9][CH2:10][C:11](Cl)=[O:12].[Cl-].[Al+3].[Cl-].[Cl-].Cl>C(=S)=S>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]2[C:3]=1[CH2:8][CH2:9][CH2:10][C:11]2=[O:12]
Reactant: O=C(Cl)CCCc1ccccc1F
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: S=C=S
Product: O=C1CCCc2c(F)cccc21
Temperature: 25 °C
Yield: 93 %

Procedure:
To the 4-(2-fluorophenyl)butyryl chloride in carbon disulfide (1.0 L) at -78° C. was added aluminum chloride (93.2 g, 0.7 mol) portionwise over a 30 min period. The mixture was warmed to room temperature for 30 min, then refluxed for 2 h. The reaction mixture was poured into a mixture of ice (500 mL) and HCl (6N, 500 mL). The carbon disulfide layer was separated, washed with saturated sodium bicarbonate and extracted with ethyl acetate. The aqueous phase was extracted with ethyl acetate. The combined extracts were dried (MgSO4) and concentrated in vacuo to give 84.2 g (93%) of 5-fluorotetralone as a tan solid. NMR (CDCl3): d 7.7 (m, 1H, ArH), 7.1 (m, 2H, ArH), 2.9 (t, 2H, CH2), 2.6 (t, 2H, CH2), 2.1 (q, 2H, CH2).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:15]=1)[C:7](=[O:14])[C:8]1[CH2:13][CH2:12][CH2:11][C:9]=1[N:10]=2.[CH:16](=O)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C[O-].[Na+]>CO>[CH:16](=[C:11]1[C:9]2[N:10]=[C:5]3[CH:4]=[CH:3][C:2]([CH3:1])=[CH:15][N:6]3[C:7](=[O:14])[C:8]=2[CH2:13][CH2:12]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: Cc1ccc2nc3c(c(=O)n2c1)CCC3
Reactant: O=Cc1ccccc1
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: Cc1ccc2nc3c(c(=O)n2c1)CCC3=Cc1ccccc1

Procedure:
7-methyl-1,2,3,10-tetrahydro-cyclopenta[d]pyrido[1,2-a]pyrimidine-10-one (5 g) was reacted with benzaldehyde (13.2 g) in methanol (200 ml) in the presence of sodium methoxide (6.8 g) at reflux temperature for 96 hours. After cooling and concentration in vacuo to a small volume the precipitate was filtered and washed with water until neutral; crystallization from CH2Cl2 /methanol gave 3-benzylidene-7-methyl-1,2,3,10-tetrahydro-cyclopenta[d]pyrido[1,2-a]pyrimidine-10-one, m.p. 197°-199° C., NMR (CDCl3) δ ppm: 2.45 (s) (3H, CH3), 3.10 (bs) (4H, C-1 and C-2 protons), 7.2-7.7 (m) (8H, =CH-- and C-5 and C-6 and phenyl protons), 8.80 (bs) (1H, C-8 proton).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:8](=[O:10])[CH3:9])[CH:5]=[CH:6][CH:7]=1.[CH3:11][Li].[Cl-].[NH4+]>C(OCC)C>[OH:10][C:8]([C:4]1[CH:3]=[C:2]([Br:1])[CH:7]=[CH:6][CH:5]=1)([CH3:11])[CH3:9]
Reactant: [Li]C
Reactant: CC(=O)c1cccc(Br)c1
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCOCC
Product: CC(C)(O)c1cccc(Br)c1
Yield: 95.8 %

Procedure:
To a solution of 3.34 g (16.8 mmol) of 3'-bromoacetophenone in dry diethyl ether (68 ml) was added 1.4M diethyl ether solution of methyllithium (18.0 ml, 25.2 mmol) in an atmosphere of argon at 0° C., and the mixture was allowed to react for 30 min. To the solution was added a saturated aqueous solution of ammonium chloride, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and then concentrated under reduced pressure. The residue thus obtained was subjected to silica gel column chromatography for separation and purification. Elution with dichloromethane-methanol yielded 3.47 g (16.1 mmol) of 3-(α-hydroxyisopropyl)-1-bromobenzene.
Reaction SMILES: [C:1]1([C:7]2[N:8]=[C:9]([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]([OH:28])=[O:27])[O:10][C:11]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:29]O>S(=O)(=O)(O)O.C(OCC)C>[C:1]1([C:7]2[N:8]=[C:9]([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]([O:28][CH3:29])=[O:27])[O:10][C:11]=2[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CO
Reactant: O=C(O)CCCCCCCCc1nc(-c2ccccc2)c(-c2ccccc2)o1
Agent: O=S(=O)(O)O
Solvent: CCOCC
Product: COC(=O)CCCCCCCCc1nc(-c2ccccc2)c(-c2ccccc2)o1
Reaction time: 2 h
Yield: 96 %

Procedure:
A mixture of 4,5-diphenyl-2-oxazole nonanoic acid (800 mg, 2 mmol), methanol (2 mL) and concentrated sulfuric acid (2 drops) was heated to reflux. After 2 hours, the solvent was evaporated and the residue partitioned between CH2Cl2 and water. The organic phase was separated, washed with saturated NaHCO3 solution, dried over sodium sulfate and concentrated in vacuo to leave an oil. Chromatography on a column of silica gel using a mixture of hexanes and diethyl ether (4:1) as eluent gave methyl 4,5-diphenyl-2-oxazolenonanoate (800 mg, 96%).
Reaction SMILES: [O:1]([C:13]1[C:18]([O:19][CH3:20])=[CH:17][C:16]([CH:21]=O)=[CH:15][C:14]=1[O:23][CH3:24])[C@@H:2]1[O:10][C@H:9]([CH2:11][OH:12])[C@H:7]([OH:8])[C@H:5]([OH:6])[C@H:3]1[OH:4].[I-:25].[CH3:26][N+:27]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:30]([CH3:37])=[CH:29][CH:28]=1.C([O-])(=O)C.[NH4+]>C(O)C>[I-:25].[C@@H:2]1([O:1][C:13]2[C:18]([O:19][CH3:20])=[CH:17][C:16]([CH:21]=[CH:37][C:30]3[C:31]4[C:36](=[CH:35][CH:34]=[CH:33][CH:32]=4)[N+:27]([CH3:26])=[CH:28][CH:29]=3)=[CH:15][C:14]=2[O:23][CH3:24])[O:10][C@H:9]([CH2:11][OH:12])[C@H:7]([OH:8])[C@H:5]([OH:6])[C@H:3]1[OH:4]
Reactant: COc1cc(C=O)cc(OC)c1O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O
Reactant: Cc1cc[n+](C)c2ccccc12
Agent: CC(=O)[O-]
Agent: [I-]
Agent: [NH4+]
Solvent: CCO
Product: COc1cc(C=Cc2cc[n+](C)c3ccccc23)cc(OC)c1O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O
Temperature: 60 °C
Reaction time: 5 h
Yield: 70.5 %

Procedure:
A suspension of 4-formyl-2,6-dimethoxyphenyl β-D-galactopyranoside (2c)(0.20 g, 0.58 mmol), 1,4-dimethylquinolinium iodide (0.17 g, 0.58 mmol) in ethanol (20 ml) containing ammonium acetate (0.15 g 1.9 mmol) was stirred at about 60° C. for 5 h. The dark orange precipitate which formed during the reaction was then filtered off and washed with ethanol followed by acetone to give (24c)(0.25 g, 70%) an orange solid.
Reaction SMILES: C(OC([N:8]1[CH2:17][C:16]([CH3:19])([CH3:18])[C:15]2[C:10](=[CH:11][C:12](Br)=[CH:13][CH:14]=2)[CH2:9]1)=O)(C)(C)C.[Cu][C:22]#[N:23].N.O>CN1CCCC1=O>[C:22]([C:12]1[CH:11]=[C:10]2[C:15]([C:16]([CH3:18])([CH3:19])[CH2:17][NH:8][CH2:9]2)=[CH:14][CH:13]=1)#[N:23]
Reactant: N#C[Cu]
Reactant: CC(C)(C)OC(=O)N1Cc2cc(Br)ccc2C(C)(C)C1
Agent: N
Solvent: CN1CCCC1=O
Solvent: O
Product: CC1(C)CNCc2cc(C#N)ccc21
Yield: 86.4 %

Procedure:
A mixture of N-tert-butyloxycarbonyl-7-bromo-4,4-dimethyl-1,2,3,4-tetrahydroisoquinoline (4.2 g, 0.01236 mol) and copper (I) cyanide (2.2 g, 0.0247 mol) in N-methylpyrrolidinone (120 ml) was heated at vigorous reflux for 2 hours. On cooling the mix was poured into 0.880 ammonia (300 ml) and water (300 ml) and extracted into ethyl acetate (4×200 ml). Combined organic extracts were washed with 1:10.880 ammonia:water (3×150 ml), water (3×200 ml) and brine (150 ml) and dried (Na2SO4). Solvent was removed in vacuo to afford the title compound as a pale brown solid (1.99 g, 86%).