Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[N+:3]([C:6]1[CH:17]=[CH:16][C:9]2[CH2:10][CH2:11][CH2:12][C:13](=[O:15])[NH:14][C:8]=2[CH:7]=1)([O-:5])=[O:4].I[CH3:19]>CN(C=O)C>[CH3:19][N:14]1[C:8]2[CH:7]=[C:6]([N+:3]([O-:5])=[O:4])[CH:17]=[CH:16][C:9]=2[CH2:10][CH2:11][CH2:12][C:13]1=[O:15]
Reactant: O=C1CCCc2ccc([N+](=O)[O-])cc2N1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CN1C(=O)CCCc2ccc([N+](=O)[O-])cc21
Reaction time: 0.25 h

Procedure:
144 mg of NaH (50%) are added to a solution of 549 mg of 8-nitro-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one in 15 ml of DMF. The reaction medium is stirred for 15 minutes and then 187 μl of iodomethane are added. The mixture is stirred for 16 hours at ambient temperature and then run into ice-cold water and extracted with ethyl acetate. The organic phase is washed with a saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue is taken up in diisopropyl ether and the insoluble material is filtered off and dried under vacuum, so as to give 405 mg of 1-methyl-8-nitro-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one in the form of a beige solid.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:30])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:12][CH2:13][CH2:14][NH:15][CH2:16][CH:17]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:6]=1.[I:31][C:32]1[CH:33]=[C:34]([CH:37]=[CH:38][CH:39]=1)[CH2:35]Br.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[CH3:1][O:2][C:3](=[O:30])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:12][CH2:13][CH2:14][N:15]([CH2:16][CH:17]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:35][C:34]2[CH:37]=[CH:38][CH:39]=[C:32]([I:31])[CH:33]=2)[CH:6]=1
Reactant: COC(=O)Cc1cccc(OCCCNCC(c2ccccc2)c2ccccc2)c1
Reactant: BrCc1cccc(I)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)Cc1cccc(OCCCN(Cc2cccc(I)c2)CC(c2ccccc2)c2ccccc2)c1
Temperature: 45 °C
Reaction time: 18 h
Yield: 80.7 %

Procedure:
To a solution of {3-[3-(2,2-diphenyl-ethylamino)-propoxy]-phenyl}-acetic acid methyl ester (3) (0.50 g, 0.0012 mol) in DMF (10 mL), was added 3-iodobenzyl bromide (0.36 g, 0.0012 mol) and powdered potassium carbonate (1.16 g, 0.0084 mol), the reaction mixture was heated and stirred at 45° C. for 18 hours. After cooling, the reaction mixture was diluted with water (30 mL) and extracted with EtOAc (3×25 mL). The combined organic extracts were washed with brine (15 mL), dried over Na2SO4, concentrated to an oil, which was purified by flash chromatography (8:2 Hexanes/EtOAc) to give the desired product as oil 0.6 g in 81% yield. 1H NMR (CDCl3) δ 7.48 (d, 1H), 7.42 (s, 1H), 7.24 (m, 5H), 7.15 (m, 6H), 6.99 (d, 1H), 6.86 (m, 2H), 6.65 (s, 1H), 6.63 (dd, 1H), 4.16 (t, 1H), 3.67 (s, 3H), 3.60 (t, 2H), 3.58 (s, 2H), 3.52 (s, 2H), 3.05 (d, 2H), 2.61 (t, 2H), 1.81 (t, 2H); 13C NMR (CDCl3) δ 173.4, 160.5, 144.7, 143.7, 139.2, 137.3, 136.6, 131.2, 130.9, 129.8, 129.7, 129.6, 129.4, 127.8, 122.7, 116.9, 114.5, 95.6, 66.9, 61.1, 59.9, 53.5, 51.8, 51.1, 42.7, 28.2.
Reaction SMILES: [NH2:1][C:2]1([CH2:46][C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][C:48]=2[F:53])[CH2:7][CH2:6][CH2:5][CH:4]([NH:8][C:9]([C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[N:16]([C:20]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)([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)[N:15]=[C:14]3[C:39]2[CH:44]=[CH:43][N:42]=[C:41]([CH3:45])[CH:40]=2)=[O:10])[CH2:3]1.[CH:54](OCC(F)(F)F)=[O:55].CCN(C(C)C)C(C)C>C1COCC1>[F:53][C:48]1[CH:49]=[CH:50][CH:51]=[CH:52][C:47]=1[CH2:46][C:2]1([NH:1][CH:54]=[O:55])[CH2:7][CH2:6][CH2:5][CH:4]([NH:8][C:9]([C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[N:16]([C:20]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[N:15]=[C:14]3[C:39]2[CH:44]=[CH:43][N:42]=[C:41]([CH3:45])[CH:40]=2)=[O:10])[CH2:3]1
Reactant: O=COCC(F)(F)F
Reactant: Cc1cc(-c2nn(C(c3ccccc3)(c3ccccc3)c3ccccc3)c3ccc(C(=O)NC4CCCC(N)(Cc5ccccc5F)C4)cc23)ccn1
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: Cc1cc(-c2nn(C(c3ccccc3)(c3ccccc3)c3ccccc3)c3ccc(C(=O)NC4CCCC(Cc5ccccc5F)(NC=O)C4)cc23)ccn1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A reaction mixture of N-(3-amino-3-(2-fluorobenzyl)cyclohexyl)-3-(2-methylpyridin-4-yl)-1-trityl-1H-indazole-5-carboxamide (0.01 mmol, 7 mg), 2,2,2-trifluoroethyl formate (0.06 mmol, 6 μL) and DIEA (10 equiv.) in THF was stirred at room temperature for overnight. The product, N-(3-(2-fluorobenzyl)-3-formamidocyclohexyl)-3-(2-methylpyridin-4-yl)-1-trityl-1H-indazole-5-carboxamide, was obtained after evaporation of solvent.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:6]([O:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:18]=[CH:17][NH:16][N:15]=3)=[CH:10][CH:9]=2)=[CH:5][CH:4]=1.[Cl:21][C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1>>[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([N:16]2[CH:17]=[CH:18][C:14]([C:11]3[CH:12]=[CH:13][C:8]([O:7][C:6]4[CH:19]=[CH:20][C:3]([O:2][CH3:1])=[CH:4][CH:5]=4)=[CH:9][CH:10]=3)=[N:15]2)=[CH:24][CH:23]=1
Reactant: OB(O)c1ccc(Cl)cc1
Reactant: COc1ccc(Oc2ccc(-c3cc[nH]n3)cc2)cc1
Product: COc1ccc(Oc2ccc(-c3ccn(-c4ccc(Cl)cc4)n3)cc2)cc1

Procedure:
By the same procedure as Example 67 Part C, 3-[4-(4-methoxy-phenoxy)-phenyl]-1H-pyrazole and 4-chlorophenylboronic acid were converted to the title compound. MS m/z: ESI+ 377.1 (M+H)+.
Reaction SMILES: [C:1]1([N:7]([C:14]2[CH:19]=[CH:18][C:17]([C:20]3[C:28]4[C:24](=[N:25][NH:26][N:27]=4)[C:23]([C:29]4[CH:34]=[CH:33][C:32]([N:35]([C:42]5[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=5)[C:36]5[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=5)=[CH:31][CH:30]=4)=[CH:22][CH:21]=3)=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:49]1[N:54]=[CH:53][CH:52]=[CH:51][N:50]=1.[H-].[Na+].CN(C)C=O>O>[C:8]1([N:7]([C:14]2[CH:15]=[CH:16][C:17]([C:20]3[C:28]4[C:24](=[N:25][N:26]([C:49]5[N:54]=[CH:53][CH:52]=[CH:51][N:50]=5)[N:27]=4)[C:23]([C:29]4[CH:34]=[CH:33][C:32]([N:35]([C:36]5[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=5)[C:42]5[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=5)=[CH:31][CH:30]=4)=[CH:22][CH:21]=3)=[CH:18][CH:19]=2)[C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: Clc1ncccn1
Reactant: c1ccc(N(c2ccccc2)c2ccc(-c3ccc(-c4ccc(N(c5ccccc5)c5ccccc5)cc4)c4n[nH]nc34)cc2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: c1ccc(N(c2ccccc2)c2ccc(-c3ccc(-c4ccc(N(c5ccccc5)c5ccccc5)cc4)c4nn(-c5ncccn5)nc34)cc2)cc1
Temperature: 120 °C

Procedure:
A mixture of Intermediate D (500 mg, 0.82 mmol), 2-chloropyrimidine (343 mg, 3.0 mmol), 60% NaH (60 mg, 1.5 mmol), and dimethlyformamide (10 mL) was stirred under argon and heated at 120° C. for 20 hours. The reaction mixture was poured into water (100 mL) and extracted with dichloromethane (4×100 mL). The extract was dried over anhydrous sodium sulfate, the volatiles were removed under reduced pressure, and the residue was chromatographed using silica gel and dichloromethane/ethyl acetate (95:5) as an eluent. The obtained product was recrystallized from ethanol to give 4,7-bis(4-(N,N-diphenylamino)phenyl)-2-(pyrimidin-2-yl)-2H-benzo[d][1,2,3]triazole (Example 12), orange crystals, 340 mg (61%). 1H NMR (400 MHz, CDCl3): δ 8.99 (d, J=5.1 Hz, 2H, pyrimidine), 8.02 (d, J=8.8 Hz, 4H, p-phenylene), 7.66 (s, 2H, benzotriazole), 7.47 (t, J=4.8 Hz, 1H, pyrimidine), 7.28 (m, 8H, Ph), 7.21 (d, J=8.4 Hz, 4H, p-phenylene), 7.18 (m, 8H, Ph), 7.05 (tt, J=7.3 and 1.1 Hz, 4H, Ph). UV-vis spectrum (dichloromethane): λmax=451 nm. Fluorimetry (dichloromethane): λmax=600 nm.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([NH2:7])=[O:6].C(=O)([O-])[O-].[K+].[K+].Br[CH2:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C(#N)C.O>[CH2:18]([O:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([NH2:7])=[O:6])[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: NC(=O)c1cccc(O)c1
Reactant: BrCCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC#N
Product: NC(=O)c1cccc(OCCc2ccccc2)c1

Procedure:
3-Hydroxybenzamide (500 mg; 3.6 mM) was dissolved in dry acetonitrile (36 ml), and to this was added potassium carbonate (0.503 g; 3.6 mmol) and 2-(bromoethyl)benzene (0.498 ml; 3.6 mmol). The mixture was heated under reflux for two days. The acetonitrile was removed under reduced pressure to yield a white solid. This was dissolved in water and extracted into dichloromethane (3×30 ml). The organics were pooled, dried over magnesium sulphate, filtered and the solvent was removed under reduced pressure to yield a white solid. This was recrystallised from boiling ethyl acetate and petrol (0.459 g; 12.51%).
Reaction SMILES: [F:1][C:2]1[C:22]([C:23]([F:26])([F:25])[F:24])=[CH:21][CH:20]=[CH:19][C:3]=1[C:4]([N:6]1[CH2:11][CH2:10][N:9](C(OC(C)(C)C)=O)[CH2:8][CH2:7]1)=[O:5].[ClH:27].O1CCOCC1>CO>[ClH:27].[F:1][C:2]1[C:22]([C:23]([F:26])([F:24])[F:25])=[CH:21][CH:20]=[CH:19][C:3]=1[C:4]([N:6]1[CH2:11][CH2:10][NH:9][CH2:8][CH2:7]1)=[O:5]
Reactant: CC(C)(C)OC(=O)N1CCN(C(=O)c2cccc(C(F)(F)F)c2F)CC1
Agent: Cl
Solvent: C1COCCO1
Solvent: CO
Product: O=C(c1cccc(C(F)(F)F)c1F)N1CCNCC1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a mixture of 7.74 g of tert-butyl 4-(2-fluoro-3-(trifluoromethyl)benzoyl)piperazine-1-carboxylate and 10 ml of methanol was added a hydrochloric acid-1,4-dioxane solution (4 M, 20 ml) followed by stirring at room temperature for 4 hours. The reaction mixture was concentrated in vacuo to give the title compound.
Reaction SMILES: [NH2:1][C:2]1[C:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[ClH:16].[CH3:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][C:26](=[NH:30])OCC)=[CH:21][CH:20]=1>C(O)C>[ClH:16].[CH2:9]([O:8][C:7]1[C:2]([NH:1][C:26](=[NH:30])[CH2:25][C:22]2[CH:23]=[CH:24][C:19]([O:18][CH3:17])=[CH:20][CH:21]=2)=[N:3][CH:4]=[CH:5][CH:6]=1)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: CCOC(=N)Cc1ccc(OC)cc1
Reactant: Nc1ncccc1OCc1ccccc1
Agent: Cl
Solvent: CCO
Product: COc1ccc(CC(=N)Nc2ncccc2OCc2ccccc2)cc1
Yield: 16.5 %

Procedure:
A mixture of 2-amino-3-benzyloxypyridine (4.0 g, 20 mmol) and ethyl 4-methoxyphenylacetimidate hydrochloride (5.04 g, 22 mmol) in ethanol (80 ml) was heated under reflux for 2 hours. Evaporation of the solvent gave an oil which was purified by flash chromatography (chloroform/methanol) to give the product (1.27 g), m.p. 75°-78° C.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:9]2([OH:14])[CH2:13][CH2:12][NH:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[F:8].C(=O)([O-])[O-].[K+].[K+].I[CH2:22][CH3:23].C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C>[F:1][C:2]1[CH:3]=[C:4]([C:9]2([OH:14])[CH2:13][CH2:12][N:11]([CH2:22][CH3:23])[CH2:10]2)[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: OC1(c2ccc(F)c(F)c2)CCNC1
Reactant: CCI
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: [Na+]
Solvent: CC#N
Product: CCN1CCC(O)(c2ccc(F)c(F)c2)C1
Temperature: 80 °C
Yield: 39.6 %

Procedure:
In a sealed tube a mixture of enantiomer E1 of 3-(3,4-difluorophenyl)pyrrolidin-3-ol (0.26 g, 1.3 mmol), acetonitrile (3 mL), potassium carbonate (0.269 g, 1.95 mmol) and iodoethane (0.20 g, 1.3 mmol) was heated under microwave irradiation at 80° C. for 25 minutes. Aqueous sodium carbonate (10%, 50 mL) was added and the aqueous phase was extracted with ethyl acetate (2×50 mL), the combined organic phase was washed with brine, dried (Na2SO4) and evaporated. Purification by HPLC on Waters OBD C18, 5 μm (MeOH/33 mM NH3, 35:65 to 50:50) gave the title compound (0.117 g). [α]D=+19.4° (methanol). The amine was converted to the fumaric acid salt and recrystallized from methanol/diethyl ether/diisopropyl ether: M.p. 136-137° C.; MS m/z (relative intensity, 70 eV) 227 (M+, 10), 207, (19), 141 (20), 72 (42), 71 (bp).
Reaction SMILES: [C:1]1(=O)CCCCC1.[CH3:8][C:9]1[CH:14]=[CH:13][C:12]([S:15]([O:18][CH2:19][C:20]2([O:26][CH3:27])[CH2:25][CH2:24]O[CH2:22][CH2:21]2)(=[O:17])=[O:16])=[CH:11][CH:10]=1>>[CH3:8][C:9]1[CH:14]=[CH:13][C:12]([S:15]([O:18][CH2:19][C:20]2([O:26][CH3:27])[CH2:25][CH2:24][CH2:1][CH2:22][CH2:21]2)(=[O:17])=[O:16])=[CH:11][CH:10]=1
Reactant: COC1(COS(=O)(=O)c2ccc(C)cc2)CCOCC1
Reactant: O=C1CCCCC1
Product: COC1(COS(=O)(=O)c2ccc(C)cc2)CCCCC1

Procedure:
This compound was synthesized from cyclohexanone following the procedure described for (4-methoxytetrahydro-2H-pyran-4-yl)methyl 4-methylbenzenesulfonate (Intermediate O).
Reaction SMILES: C([O:4][C@@H:5]1[C@H:11]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=2[Cl:21])[C@@H:10]([CH2:22][O:23][CH2:24][C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][C:26]=2[Cl:32])[O:9][C@@H:6]1[O:7][CH3:8])(=O)C>C([O-])([O-])=O.[K+].[K+]>[Cl:21][C:15]1[CH:16]=[C:17]([Cl:20])[CH:18]=[CH:19][C:14]=1[CH2:13][O:12][C@@H:11]1[C@@H:10]([CH2:22][O:23][CH2:24][C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][C:26]=2[Cl:32])[O:9][C@H:6]([O:7][CH3:8])[C@@H:5]1[OH:4]
Reactant: CO[C@H]1O[C@H](COCc2ccc(Cl)cc2Cl)[C@@H](OCc2ccc(Cl)cc2Cl)[C@H]1OC(C)=O
Agent: O=C([O-])[O-]
Agent: [K+]
Product: CO[C@H]1O[C@H](COCc2ccc(Cl)cc2Cl)[C@@H](OCc2ccc(Cl)cc2Cl)[C@H]1O
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 101.6 %

Procedure:
A mixture of 2-O-acetyl-3,5-bis-O-(2,4-dichlorophenylmethyl)-1-O-methyl-α-D-ribofuranose [for preparation, see: Helv. Chim. Acta 78: 486 (1995)] (52.4 g, 0.10 mol) in methanolic K2CO3 (500 mL, saturated at room temperature) was stirred at room temperature for 45 min. and then concentrated under reduced pressure. The oily residue was suspended in CH2Cl2 (500 mL), washed with water (300 mL+5×200 mL) and brine (200 mL), dried (Na2SO4), filtered, and concentrated to give the title compound (49.0 g) as colorless oil, which was used without further purification in Step B below.
Reaction SMILES: [CH2:1]1[CH2:13][O:12][C:11]2[CH:10]=[CH:9][C:5]([CH2:6][CH2:7][NH2:8])=[CH:4][C:3]=2[O:2]1.Cl[C:15]1[C:16]2[CH:29]=[C:28]([N+:30]([O-:32])=[O:31])[S:27][C:17]=2[N:18]=[C:19]([C:21]2[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=2)[N:20]=1>>[N:23]1[CH:24]=[CH:25][CH:26]=[C:21]([C:19]2[N:20]=[C:15]([NH:8][CH2:7][CH2:6][C:5]3[CH:9]=[CH:10][C:11]4[O:12][CH2:13][CH2:1][O:2][C:3]=4[CH:4]=3)[C:16]3[CH:29]=[C:28]([N+:30]([O-:32])=[O:31])[S:27][C:17]=3[N:18]=2)[CH:22]=1
Reactant: NCCc1ccc2c(c1)OCCO2
Reactant: O=[N+]([O-])c1cc2c(Cl)nc(-c3cccnc3)nc2s1
Product: O=[N+]([O-])c1cc2c(NCCc3ccc4c(c3)OCCO4)nc(-c3cccnc3)nc2s1

Procedure:
With the procedure of Example 1, the reaction of 3,4-ethylenedioxyphenethylamine with 4-chloro-2-(pyridin-3-yl)-6-nitro-thieno-[2,3-d]-pyrimidine yields 2-(pyridin-3-yl)-4-(3,4-ethylenedioxyphenethylamino)-6-nitro-thieno-[2,3-d]-pyrimidine.
Reaction SMILES: [CH3:1][C:2]([OH:11])([CH3:10])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[NH2:9].[CH3:12][C:13]([CH3:15])=O>C1C=CC=CC=1>[CH3:12][C:13]1([CH3:15])[O:11][C:2]([CH3:1])([CH3:10])[C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[NH:9]1
Reactant: CC(C)=O
Reactant: CC(C)(O)c1ccccc1N
Solvent: c1ccccc1
Product: CC1(C)Nc2ccccc2C(C)(C)O1
Yield: 27.2 %

Procedure:
A solution of 15 g (0.1 mol) α,α-dimethyl-2-aminobenzyl alcohol and 5.7 g (0.1 mol) acetone in 120 ml of benzene was heated under reflux in a Dean-Stark trap for 3 hours. About 1.5 ml of water was separated from the reaction mixture. The benzene solution was then evaporated to give an oil which solidified on standing. Recrystallization from ethanol-water gave 5.2 g 2,2,4,4-tetramethyl-1,2-dihydro-4H-3,1-benzoxazine, as a white solid.
Reaction SMILES: [CH2:1]1[O:9][C:8]2[CH:7]=[CH:6][C:5]([CH2:10][C:11](O)=O)=[CH:4][C:3]=2[O:2]1.B.C1C[O:18]CC1>C1COCC1>[CH2:1]1[O:9][C:8]2[CH:7]=[CH:6][C:5]([CH:10]([OH:18])[CH3:11])=[CH:4][C:3]=2[O:2]1
Reactant: C1CCOC1
Reactant: O=C(O)Cc1ccc2c(c1)OCO2
Agent: B
Product: CC(O)c1ccc2c(c1)OCO2
Temperature: 25 °C
Reaction time: 1 h
Yield: 98 %

Procedure:
To a solution of 2-(3,4-methylenedioxy)phenylacetic acid (5 g, 25.75 mmol) in anhydrous THF (20 ml) at 0° C. was added BH3THF (40 ml, 1.0 M in THF). The mixture was stirred at room temperature for 1 h. To work up, THF was evaporated on a rotavap. The residue was treated with water (100 ml) Acidified and extracted with ether (2×100ml). Removal of the solvent under reduced pressure gave 2-(3,4-methylenedioxy)phenyl-1-ethanol as an oil (4.7 g, 98% yield).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N+:14]([O-])=O)=[C:7]([CH:9]2[O:13][CH2:12][CH2:11][O:10]2)[CH:8]=1.C(OCC)(=O)C>[Pt](=O)=O.O.O.O.C([O-])(=O)C.[Na+]>[O:10]1[CH2:11][CH2:12][O:13][CH:9]1[C:7]1[CH:8]=[C:3]([O:2][CH3:1])[CH:4]=[CH:5][C:6]=1[NH2:14]
Reactant: COc1ccc([N+](=O)[O-])c(C2OCCO2)c1
Agent: O=[Pt]=O
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Product: COc1ccc(N)c(C2OCCO2)c1
Yield: 100 %

Procedure:
2-(5-Methoxy-2-nitrophenyl)-1,3-dioxolane (15.00 g, 0.06661 mol), platinum dioxide (900 mg, 0.004 mol) and sodium acetate trihydrate (700 mg, 0.005 mol) were placed in a pressure flask, followed by ethyl acetate (400 mL, 4 mol). The reaction mixture was then purged under N2 for at least 3 times, and H2 was introduced (purged 3 times) and maintained at 52 psi for 3 hours. The reaction mixture was then filtered, and solvent was removed to give a pure product (13 g, 100%). 1H NMR (CHLOROFORM-d) δ: 6.96 (d, J=2.8 Hz, 1H), 6.76 (dd, J=8.5, 3.0 Hz, 1H), 6.64 (d, J=8.5 Hz, 1H), 5.84 (s, 1H), 4.00-4.18 (m, 4H), 3.89 (br. s., 2H). MS (M+1): 196.10.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:26])[CH:5]([C:9]1([S:22][CH2:23][CH2:24][OH:25])[CH2:14][CH2:13][N:12]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:11][CH2:10]1)[NH:6]C=O)[CH3:2].Cl>C(O)C>[NH2:6][CH:5]([C:9]1([S:22][CH2:23][CH2:24][OH:25])[CH2:14][CH2:13][N:12]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:11][CH2:10]1)[C:4]([O:3][CH2:1][CH3:2])=[O:26]
Reactant: CCOC(=O)C(NC=O)C1(SCCO)CCN(Cc2ccccc2)CC1
Agent: Cl
Solvent: CCO
Product: CCOC(=O)C(N)C1(SCCO)CCN(Cc2ccccc2)CC1

Procedure:
Ethyl{1-benzyl-4-[(2-hydroxyethyl)sulfanyl]-4-piperidinyl}(formylamino)acetate (2.8 g, 7.3 mmol) was dissolved in 50 ml of ethanol and 5N hydrochloric acid (4 ml) and refluxed for 2 h. The reaction mixture was then concentrated to dryness to provide ethyl amino{1-benzyl-4-[(2-hydroxyethyl)sulfanyl]-4-piperidinyl}acetate as a brown oil which was used for the next step with out purification. Yield: 3.0 g (quantitative); Electrospray Mass Spec: 353 (M+H)+.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].O[CH2:13][CH2:14][CH2:15][NH:16][C:17](=[O:26])[O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[CH2:19]([O:18][C:17]([NH:16][CH2:15][CH2:14][CH2:13][O:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6])=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: COC(=O)c1cccc(O)c1
Reactant: O=C(NCCCO)OCc1ccccc1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COC(=O)c1cccc(OCCCNC(=O)OCc2ccccc2)c1
Yield: 38.9 %

Procedure:
A mixture of methyl 3-hydroxybenzoate (609 mg, 4 mmol), benzyl N-(3-hydroxypropyl)carbamate (754 mg, 3.6 mmol) and polymer supported triphenylphosphine (PS—PPh3) (4 g, 12 mmol) in THF (40 mL) was stirred and diethyl azodicarboxylate (948 mg, 5.44 mmol) was added as a solution in THF (4 mL). The mixture was stirred for 16 h then was filtered and washed with DCM and concentrated by evaporation. The residue was purified by chromatography eluting with DCM to give the title compound (481 mg, 35%) as an oil; 1H NMR δ 1.85-1.92 (2H, m), 3.19 (2H, q), 3.86 (3H, s), 4.05 (2H, t), 5.02 (2H, s), 7.20-7.22 (1H, m), 7.29-7.38 (5H, m), 7.42-7.45 (2H, m), 7.53-7.56 (1H, m).
Reaction SMILES: Cl[N:2]1[C:6](=O)[CH2:5][CH2:4]C1=O.[F:9][C:10]1[C:18]([I:19])=[CH:17][CH:16]=[CH:15][C:11]=1[CH:12]=[N:13][OH:14].O.C1(N)CC1>CN(C=O)C>[CH:6]1([NH:2][C:12](=[N:13][OH:14])[C:11]2[CH:15]=[CH:16][CH:17]=[C:18]([I:19])[C:10]=2[F:9])[CH2:4][CH2:5]1
Reactant: ON=Cc1cccc(I)c1F
Reactant: O=C1CCC(=O)N1Cl
Agent: NC1CC1
Solvent: CN(C)C=O
Solvent: O
Product: ON=C(NC1CC1)c1cccc(I)c1F
Temperature: 55 °C
Reaction time: 0.25 h
Yield: 97.6 %

Procedure:
N-chlorosuccinimide (1.20 g, 8.9 mmol) was added portionwise to a stirred solution of 2-fluoro-3-iodobenzaldehyde oxime (preparation 22e, 2.15 g, 8.1 mmol) in N,N′-dimethylformamide (3 mL) and the mixture was stirred for 15 minutes at 55° C. After cooling to ambient temperature, water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried (MgSO4) and evaporated. The residue was taken up in tetrahydrofuran (10 mL), cooled by means of an ice-water bath and cyclopropylamine (2.90 mL, 41.9 mmol) was added dropwise. After stirring 3 hours at room temperature, water was added to the reaction and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried (MgSO4) and evaporated to give the title compound (2.53 g, 96%) as a white solid.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)=[CH:4][C:3]=1[F:17].Cl[C:19](OC(Cl)(Cl)Cl)=[O:20]>C1(C)C=CC=CC=1>[F:16][C:13]1[CH:14]=[CH:15][C:10]([CH2:9][O:8][C:5]2[CH:6]=[CH:7][C:2]([N:1]=[C:19]=[O:20])=[C:3]([F:17])[CH:4]=2)=[CH:11][CH:12]=1
Reactant: O=C(Cl)OC(Cl)(Cl)Cl
Reactant: Nc1ccc(OCc2ccc(F)cc2)cc1F
Solvent: Cc1ccccc1
Product: O=C=Nc1ccc(OCc2ccc(F)cc2)cc1F
Temperature: 25 °C
Reaction time: 1 h
Yield: 135.9 %

Procedure:
To a solution of 6.50 g (0.0276 mole) of 4-fluorophenylmethyl 4-amino-3-fluorophenyl ether in toluene, stirring at room temperature, was slowly added 3.95 g (0.020 mole) of trichloromethyl chloroformate. During the addition a thick precipitate formed. Upon completion of addition, the reaction mixture was stirred for one hour at room temperature and then at reflux for approximately seventeen hours. The toluene was removed by distillation, leaving 7.10 g of 4-(4-fluorophenylmethoxy)-2-fluorophenyl isocyanate.
Reaction SMILES: [CH3:1][C@@H:2]([C@@H:9]1[C@@:13]2([CH3:28])[CH2:14][CH2:15][CH2:16]/[C:17](=[CH:18]\[CH:19]=[C:20]3\[CH2:21][C@@H:22]([OH:27])[CH2:23][CH2:24][C:25]\3=[CH2:26])/[C@@H:12]2[CH2:11][CH2:10]1)[CH2:3][CH2:4][CH2:5][CH:6]([CH3:8])[CH3:7].[C:29](Cl)(=[O:36])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>N1C=CC=CC=1>[C:29]([O:27][C@H:22]1[CH2:23][CH2:24][C@@:25]2([CH3:26])[C@@H:20]([CH2:19][CH2:18][C@@H:17]3[C@@H:16]2[CH2:15][CH2:14][C@@:13]2([CH3:28])[C@H:12]3[CH2:11][CH2:10][C@@H:9]2[C@H:2]([CH3:1])[CH2:3][CH2:4][CH2:5][CH:6]([CH3:7])[CH3:8])[CH2:21]1)(=[O:36])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1
Reactant: C=C1CC[C@H](O)C/C1=C/C=C1\CCC[C@]2(C)[C@@H]([C@H](C)CCCC(C)C)CC[C@@H]12
Reactant: O=C(Cl)c1ccccc1
Solvent: c1ccncc1
Product: CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@@H](OC(=O)c5ccccc5)CC[C@]4(C)[C@H]3CC[C@]12C
Temperature: 0 °C
Reaction time: 0.33 h

Procedure:
To a solution of 7-dehydrocholesterol (1, 50.0 g, 0.13 mol; Aldrich Chemical Co.) dissolved in dry pyridine (120 mL) was added, with stirring, benzoyl chloride (28 mL, 34.1 g, 0.24 mol). After the addition, the reaction mixture was heated at reflux for 5 min and was then left at ambient temperature for 20 min. The reaction mixture was poured with stirring into ice water (1.5 L). The precipitate was allowed to rest for 1 h and was then taken up on a filter and washed successively with water (350 mL), 5% sodium bicarbonate (200 mL), water (350 mL) and finally acetone (5×25 mL). The crude material was air dried and subsequently recrystallized. The crude material was dissolved in hot chloroform (100 mL) and to this solution was added acetone (250 mL). The flask was left at ambient temperature and then at -20° C. overnight. The crystalline material was collected by filtration, and then washed with a small amount of acetone. Total yield compound 2 after drying, 58.3 g (92%). Melting point and spectral data agree with previous reported values (Wilson et al., J. Org. Chem. 53:1713 (1988)).