Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]([Cl:3])=[CH2:2].[Cl:4][C:5]([Cl:11])(Cl)[P:6]([Cl:9])([Cl:8])=[O:7].[Cl-:12].C([NH+](CC)CC)C>C(#N)C.C1(C(C(C2C=CC=CC=2)O)=O)C=CC=CC=1>[Cl:4][C:5]([Cl:11])([P:6]([Cl:9])([Cl:8])=[O:7])[CH2:2][CH:1]([Cl:12])[Cl:3]
Reactant: O=P(Cl)(Cl)C(Cl)(Cl)Cl
Reactant: C=CCl
Reactant: [Cl-]
Agent: CC[NH+](CC)CC
Agent: O=C(c1ccccc1)C(O)c1ccccc1
Solvent: CC#N
Product: O=P(Cl)(Cl)C(Cl)(Cl)CC(Cl)Cl
Yield: 926.1 %

Procedure:
6.25 g (0.1 mole) vinyl chloride, 23.6 g (0.1 mole) trichloromethane phosphonic dichloride, 540 mg (2 mmole) ferric chloride hexahydrate, 412 mg (3 mmole) triethylammonium chloride, and 424 mg (2 mmole) benzoin were heated in 30 ml acetonitrile in an ampoule at 100° during 15 hours. After opening of the ampoule, and evaporating unconverted vinyl chloride, the reaction product was diluted with methylene chloride, washed twice with ice-cold 1N aqueous hydrochloric acid and dried on calcium chloride. The solvent was distilled at atmospheric pressure, and unconverted phosphonic dichloride sublimed at 25 mm and 120°. The remainder was fractionated in vacuo, giving 8.3 g 1,1,3,3-tetrachloropropane-1-phosphonic dichloride, bp/0.1: 66°-67°; containing 70.3% Cl (Calc. for C3H3Cl6OP: 71.0%).
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[N:12]=[C:11]([CH2:19][S:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[C:10]=1[CH3:28])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClC1C=CC=C(C(OO)=[O:37])C=1.[OH-].[Na+]>ClCCl>[CH2:1]([O:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[N:12]=[C:11]([CH2:19][S:20]([CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])=[O:37])[C:10]=1[CH3:28])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCCCCCCSCc1nc2ccccc2c(OCc2ccccc2)c1C
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Product: CCCCCCCS(=O)Cc1nc2ccccc2c(OCc2ccccc2)c1C
Temperature: 25 °C
Reaction time: 5 h
Yield: 68 %

Procedure:
To a solution of 4-(benzyloxy)-2-[(heptylsulfanyl)methyl]-3-methylquinoline (106 mg) in dichloromethane (5 mL) was added m-chloroperbenzoic acid (75%, 68 mg) at −30° C., followed by stirring for 5 hours while warming to room temperature. A 0.2M aqueous sodium hydroxide solution (20 mL) was added to the reaction mixture, followed by extraction with chloroform (50 mL). The organic layer was washed sequentially with water and saturated brine and then dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: chloroform/methanol=10/1) to obtain 4-(benzyloxy)-2-[(heptylsulfinyl)methyl]-3-methylquinoline (75 mg).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]([C:17]2[C:25]3[C:20](=[C:21]([C:26]([F:29])([F:28])[F:27])[CH:22]=[CH:23][CH:24]=3)[NH:19][N:18]=2)=[O:16])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].I[CH:33]([CH3:35])[CH3:34]>CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]([C:17]2[C:25]3[C:20](=[C:21]([C:26]([F:29])([F:27])[F:28])[CH:22]=[CH:23][CH:24]=3)[N:19]([CH:33]([CH3:35])[CH3:34])[N:18]=2)=[O:16])=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(c1ccc(OCc2ccccc2)cc1)c1n[nH]c2c(C(F)(F)F)cccc12
Reactant: CC(C)I
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)n1nc(C(=O)c2ccc(OCc3ccccc3)cc2)c2cccc(C(F)(F)F)c21
Temperature: 50 °C
Reaction time: 24 h
Yield: 82.1 %

Procedure:
To a solution of [4-(benzyloxy)phenyl](7-trifluoromethyl-1H-indazol-3-yl)methanone (0.20 g, 0.5 mmol) in 3 mL DMF was added in one portion sodium hydride (0.020 g, 0.5 mmol, 60% in oil). After the gas evolution ceased, 2-iodopropane (0.075 mL, 0.75 mmol) was added and the reaction was stirred at ambient to 50° C. for 24 hours. The cool reaction mixture was partitioned with EtOAc and 1 N HCl. The organic phase was washed with brine and dried (Na2SO4). Removal of the solvent in vacuo provided 0.18 g of the title compound which was used directly in the following step.
Reaction SMILES: [C:1]1(C2C=NC(=O)C(=O)C=2C2C=CC=CC=2)C=CC=C[CH:2]=1.C1OCCOCCOCCOCCOCCOC1.[NH2:39][C@H:40]([CH2:47][C:48]([OH:50])=[O:49])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1>C(Cl)Cl>[CH2:1]([O:49][C:48](=[O:50])[CH2:47][C@H:40]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[NH2:39])[CH3:2]
Reactant: O=C1N=CC(c2ccccc2)=C(c2ccccc2)C1=O
Reactant: N[C@H](CC(=O)O)c1ccccc1
Agent: C1COCCOCCOCCOCCOCCO1
Solvent: ClCCl
Product: CCOC(=O)C[C@@H](N)c1ccccc1

Procedure:
In this example, 0.32 ml of the diphenyl-diketo-pyridine-18-crown-6 was coated on polystyrene, and further coated with CH2Cl2, as described in Example 4. The resulting coated ligand-bound solid support was then placed in a column. A 25° C. 3 ml racemic source solution containing 50 mMolar R and S enantiomers of the ethyl ester of β-phenylalanine, 0.01 M HClO4, and 0.5 M LiClO4 was drawn through the column at a 0.012 ml/min flow rate. Next, a 2 ml aqueous solution of 0.5 M LiCO4 and 0.01 M HClO4 was passed through the column to wash out the loading solution remaining in the column. The β-phenylalanine ester loaded on the column was then eluted in 3 ml of deionized water at 25° C. at a flow rate of from 0.01–0.02 ml/min in two 1.5 ml aliquots.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]3[CH:15]=[C:14]([C:16]4[S:17][C:18]5[C:24]([C:25]6[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=6)=[C:23]([C@H:32]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])[C:33]([O:35][CH2:36][CH3:37])=[O:34])[C:22]([CH3:43])=[CH:21][C:19]=5[N:20]=4)[CH:13]=[CH:12][N:11]=3)=[CH:7][CH:8]=2)[CH:3]=[N:2]1.C([O-])([O-])=O.[Cs+].[Cs+].Cl[C:51]([F:57])([F:56])C(OC)=O>CN(C=O)C>[C:39]([O:38][C@@H:32]([C:23]1[C:22]([CH3:43])=[CH:21][C:19]2[N:20]=[C:16]([C:14]3[CH:13]=[CH:12][N:11]=[C:10]([C:6]4[CH:5]=[C:4]5[C:9](=[CH:8][CH:7]=4)[N:1]([CH:51]([F:57])[F:56])[N:2]=[CH:3]5)[CH:15]=3)[S:17][C:18]=2[C:24]=1[C:25]1[CH:26]=[CH:27][C:28]([Cl:31])=[CH:29][CH:30]=1)[C:33]([O:35][CH2:36][CH3:37])=[O:34])([CH3:42])([CH3:41])[CH3:40]
Reactant: CCOC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc(-c3ccnc(-c4ccc5[nH]ncc5c4)c3)sc2c1-c1ccc(Cl)cc1
Reactant: COC(=O)C(F)(F)Cl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CCOC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc(-c3ccnc(-c4ccc5c(cnn5C(F)F)c4)c3)sc2c1-c1ccc(Cl)cc1
Temperature: 60 °C

Procedure:
To a solution of (S)-ethyl 2-(2-(2-(1H-indazol-5-yl)pyridin-4-yl)-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate (20 mg, 0.0327 mmol) in DMF (1 mL) was added Cs2CO3 (53 mg, 0.163 mmol), methyl 2-chloro-2,2-difluoroacetate (4 μL, 0.039 mmol). The reaction mixture was heated at 60° C. overnight. Then more methyl 2-chloro-2,2-difluoroacetate (6 μL, 0.058 mmol) was added and heated at 60° C. for 1 day. The reaction mixture was washed by water, extracted by EtOAc, the organic phase was dried over MgSO4, filtered, concentrated down, purified by silica gel column, eluting by 0-50% EtOAc in hexanes to give (S)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-2-(2-(1-(difluoromethyl)-1H-indazol-5-yl)pyridin-4-yl)-5-methylbenzo[d]thiazol-6-yl)acetate LCMS-ESI+: calc'd for C35H31ClF2N4O3S: 661.2 (M+H+); found: 661.2; and (S)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-2-(2-(2-(difluoromethyl)-2H-indazol-5-yl)pyridin-4-yl)-5-methylbenzo[d]thiazol-6-yl)acetate. LCMS-ESI+: calc'd for C35H31ClF2N4O3S: 661.2 (M+H+); found: 661.3.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([N:12]([CH3:22])[S:13]([C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)(=[O:15])=[O:14])[N:11]=1)[C:5]([O:7]C)=[O:6].CO.[OH-].[Na+].Cl>CCOC(C)=O.C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([N:12]([CH3:22])[S:13]([C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)(=[O:15])=[O:14])[N:11]=1)[C:5]([OH:7])=[O:6]
Reactant: COC(=O)c1cc(Cl)nc(N(C)S(=O)(=O)c2cccnc2)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Solvent: CCOC(C)=O
Product: CN(c1cc(C(=O)O)cc(Cl)n1)S(=O)(=O)c1cccnc1
Reaction time: 1 h
Yield: 87.9 %

Procedure:
To a solution of methyl 2-chloro-6-[methyl(pyridin-3-ylsulfonyl)amino]isonicotinate (3.12 g, 9.13 mmol) in 1:1 MeOH:THF (60 mL total) was added 1N NaOH solution (27 mL, 27.4 mmol). After 1 h, reaction was concentrated in vacuo. Reaction was diluted with EtOAc (100 mL) and acidified with 1N HCl (50 mL) solution. The aqueous solution was extracted with EtOAc (100 mL×3). The combined organics were washed with brine (100 mL), dried over Mg2SO4, filtered, and concentrated in vacuo to give 2.63 g (88%) of 2-chloro-6-[methyl(pyridin-3-ylsulfonyl)amino]isonicotinic acid as a white solid. LC/MS [M+H]+=328.1.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]([C@H:8]1[NH:11][C:10](=[O:12])[C@@H:9]1[C@H:13]([O:15][C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17])[CH3:14])=[CH2:7])=[O:5])[CH3:2].[BH4-].[Na+]>C(O)(C)C.O.C(OCC)(=O)C.[Ni](Cl)Cl>[CH2:1]([O:3][C:4]([CH:6]([C@H:8]1[NH:11][C:10](=[O:12])[C@@H:9]1[C@H:13]([O:15][C:16]([O:18][CH2:19][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)=[O:17])[CH3:14])[CH3:7])=[O:5])[CH3:2]
Reactant: C=C(C(=O)OCC)[C@H]1NC(=O)[C@@H]1[C@@H](C)OC(=O)OCc1ccccc1
Agent: Cl[Ni]Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CC(C)O
Solvent: CCOC(C)=O
Solvent: O
Product: CCOC(=O)C(C)[C@H]1NC(=O)[C@@H]1[C@@H](C)OC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of (3S,4S)-4-(1-ethoxycarbonylethenyl)-3-(1-(R)-benzyloxycarbonyloxyethyl)-2-azetidinone (1.04 g) in isopropanol (20 ml) and water (10 ml) was treated with sodium borohydride (230 mg) in the presence of nickel chloride (40 mg) at 0°-5° C. for 15 minutes. After stirring at room temperature for additional 1 hour, the reaction mixture was diluted with ethyl acetate (300 ml), washed with brine and dried over anhydrous sodium sulfate. Filtration and concentration of the filtrate in vacuo gave an oily residue, which was purified by silica gel chromatography to yield (3S,4S)-4-(1-ethoxycarbonylethyl)-3-(1-(R)-benzyloxycarbonyloxyethyl)-2-azetidinone.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([OH:8])[CH:7]=1.[C:9](OC(=O)C)(=[O:11])[CH3:10].C(N(CC)CC)C>C1COCC1.C(OCC)C>[C:9]([O:8][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([Br:1])[CH:7]=1)(=[O:11])[CH3:10]
Reactant: Oc1cncc(Br)c1
Reactant: CC(=O)OC(C)=O
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Solvent: CCOCC
Product: CC(=O)Oc1cncc(Br)c1
Temperature: 25 °C
Yield: 84 %

Procedure:
A mixture of 3-bromo-5-hydroxypyridine (9.00 g, 51.7 mmol), acetic anhydride (6.0 mL) and triethylamine (12.0 mL) in THF (50 mL) was heated to reflux overnight, cooled to room temperature, diluted with diethyl ether, washed with water, 5% NaHCO3, water, and brine, dried (MgSO4), filtered, and concentrated to provide the desired product (9.37 g, 84%).
Reaction SMILES: [NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]2[N:9]=[C:10]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([CH:24]4[CH2:29][CH2:28][N:27]([CH:30]5[CH2:34][CH2:33][CH2:32][CH2:31]5)[CH2:26][CH2:25]4)=[CH:20][CH:19]=3)[C:11]([C:14]([NH2:16])=[O:15])=[N:12][CH:13]=2)[CH2:3]1.[CH:35](O)=[O:36].CCN(C(C)C)C(C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH:30]1([N:27]2[CH2:28][CH2:29][CH:24]([C:21]3[CH:20]=[CH:19][C:18]([NH:17][C:10]4[C:11]([C:14]([NH2:16])=[O:15])=[N:12][CH:13]=[C:8]([N:4]5[CH2:5][CH2:6][CH2:7][C@@H:2]([NH:1][CH:35]=[O:36])[CH2:3]5)[N:9]=4)=[CH:23][CH:22]=3)[CH2:25][CH2:26]2)[CH2:31][CH2:32][CH2:33][CH2:34]1
Reactant: O=CO
Reactant: NC(=O)c1ncc(N2CCC[C@@H](N)C2)nc1Nc1ccc(C2CCN(C3CCCC3)CC2)cc1
Agent: F[P-](F)(F)(F)(F)F
Agent: c1ccc2c(c1)nnn2O[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: NC(=O)c1ncc(N2CCC[C@@H](NC=O)C2)nc1Nc1ccc(C2CCN(C3CCCC3)CC2)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
(R)-5-(3-Aminopiperidin-1-yl)-3-(4-(1-cyclopentylpiperidin-4-yl)phenylamino)pyrazine-2-carboxamide (436) (50 mg, 0.1 mmol) was dissolved in 4 mL DMF. To it were added formic acid (20 μL, 0.5 mmol), DIEA (180 μL, 1.0 mmol) and then PyBOP (105 mg, 0.2 mmol). The mixture was stirred at RT for 2 hours, quenched with 0.3 mL TFA, and directly subjected to reverse phase preparative HPLC using 5 mM HCl (aq) and nest MeCN to isolate the title compound, (R)-3-(4-(1-cyclopentylpiperidin-4-yl)phenylamino)-5-(3-formamidopiperidin-1-yl)pyrazine-2-carboxamide (437), as HCl salt (24 mg). LC-MS (ESI): m/z (M+1) 492.7. UV: λ=267, 276, 305, 335, 372 nm. Proton NMR (CD3OD): δ 8.06 (1H, s), 7.65 (1H, s), 7.58 (2H, d, J=8.5 Hz), 7.21 (2H, d, J=8.5 Hz), 4.19 (1H, m), 4.01 (1H, m), 3.93 (1H, m), 3.71 (2H, d, J=12.0 Hz), 3.54 (1H, m), 3.46 (1H, m), 3.38 (1H, m), 3.12 (2H, m), 2.86 (1H, m), 2.22-1.66 (16H, m) ppm.
Reaction SMILES: F[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12].[NH2:14][CH2:15][CH:16]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[OH:17].C(N(CC)C(C)C)(C)C>CCO>[OH:17][CH:16]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH2:15][NH:14][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12]
Reactant: NCC(O)c1ccccc1
Reactant: O=C(O)c1ccc(F)c([N+](=O)[O-])c1
Solvent: CCO
Solvent: CCN(C(C)C)C(C)C
Product: O=C(O)c1ccc(NCC(O)c2ccccc2)c([N+](=O)[O-])c1
Temperature: 25 °C

Procedure:
A flask, containing 4-fluoro-3-nitrobenzoic acid (8.00 g, 43.2 mmol) and 2-amino-1-phenylethanol (8.89 g, 64.8 mmol) dissolved in EtOH (80 mL), was purged with N2. Anh. N,N-diisopropylethylamine (19 mL, 108 mmol) was added and the reaction mixture was heated at reflux for 24 h. Later the reaction was cooled to rt and concentrated under reduced pressure. The solid residue was dissolved in EtOAc, washed (1 M aq HCl (3×), H2O (2×), brine), dried (Na2SO4) and evaporated to dryness to afford the title compound as a bright yellow solid; 1H NMR (400 MHz, DMSO-d6) δ 12.80 (s, 1H), 8.67 (t, J=5.2 Hz, 1H), 8.61 (d, J=2.0 Hz, 1H), 7.92 (ddd, J=0.4 Hz, 2.0 Hz, 9.2 Hz, 1H), 7.46 (d, J=8.4 Hz, 2H), 7.36 (t, 7.2 Hz, 2H), 7.28 (tt, J=1.2 Hz, 6.8 Hz, 1H), 7.18 (d, J=9.2 Hz, 1H), 5.89 (d, J=4.4 Hz, 1H), 4.91 (q, J=3.6 Hz, 1H), 3.72-3.63 (m, 1H), 3.53-3.45 (m, 1H). MS (ES+): m/z 285.1 (100) [MH+-18]; HPLC: tR=2.80 min (OpenLynx, polar—5 min).
Reaction SMILES: [Cl:1][SiH2:2][Cl:3].[CH2:4]=[CH:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]>>[CH2:21]([SiH:2]([Cl:3])[Cl:1])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH3:4]
Reactant: Cl[SiH2]Cl
Reactant: C=CCCCCCCCCCCCCCCCC
Product: CCCCCCCCCCCCCCCCCC[SiH](Cl)Cl
Reaction time: 30 h

Procedure:
Dichlorosilane in an amount of 60.6 g (0.6 mol), 176.4 g of 1-octadecene (0.7 mol) and 0.07 mol % of RhCl(PPh)3 (relative to dichlorosilane) were charged in a 500 ml pressure-proof stainless steel reactor. After sealing, reaction was carried out at 130° C. for 30 hours. The reacted liquid was distilled in vacuo to give n-octadecyldichlorosilane (n--C18H37SiHCl2).
Reaction SMILES: Cl[C:2]1[C:11]2[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=2[N:5]=[C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:3]=1.[NH2:18][CH2:19][C:20]([N:22]([CH2:26][CH2:27][CH3:28])[CH2:23][CH2:24][CH3:25])=[O:21].C(N(CC)CC)C.O>C(Cl)(Cl)Cl>[C:12]1([C:4]2[N:3]=[C:2]([NH:18][CH2:19][C:20]([N:22]([CH2:26][CH2:27][CH3:28])[CH2:23][CH2:24][CH3:25])=[O:21])[C:11]3[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=3[N:5]=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: Clc1nc(-c2ccccc2)nc2c1CCCC2
Reactant: CCCN(CCC)C(=O)CN
Solvent: O
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: CCCN(CCC)C(=O)CNc1nc(-c2ccccc2)nc2c1CCCC2
Temperature: 150 °C
Reaction time: 3 h
Yield: 86.8 %

Procedure:
A mixture of 4-chloro-5,6,7,8-tetrahydro-2-phenylquinazoline (1.0 g), 2-amino-N,N-dipropylacetamide (0.78 g) and triethylamine (0.5 g) is refluxed with stirring at 150° C. for three hours. To the reaction mixture are added water and chloroform, and the chloroform layer is separated, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (eluent; chloroform), and recrystallized from a mixture of diethyl ether and n-hexane to give the desired compound (1.3 g), m.p. 87-88° C.
Reaction SMILES: IC.[CH3:3]N(C)C=O.C(=O)([O-])[O-].[K+].[K+].[CH:14]([O:17][NH:18][C:19](=[O:31])[C:20](=[N:26][O:27][CH:28]([CH3:30])[CH3:29])[N:21]1[CH:25]=[N:24][CH:23]=[N:22]1)([CH3:16])[CH3:15]>O>[CH:28]([O:27][N:26]=[C:20]([N:21]1[CH:25]=[N:24][CH:23]=[N:22]1)[C:19](=[N:18][O:17][CH:14]([CH3:16])[CH3:15])[O:31][CH3:3])([CH3:30])[CH3:29]
Reactant: CN(C)C=O
Reactant: CC(C)ON=C(C(=O)NOC(C)C)n1cncn1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CI
Product: COC(=NOC(C)C)C(=NOC(C)C)n1cncn1
Temperature: 25 °C
Reaction time: 20 h
Yield: 29 %

Procedure:
0.22 g (1.55 mmol) of iodomethane was added, with ice-cooling, to 5 ml of an N,N-dimethylformamide solution containing 0.22 g (1.59 mmol) of potassium carbonate and 0.4 g (1.57 mmol) of the N-isopropoxy-2-isopropoxyimino-2-(1H-1,2,4-triazol-1-yl)acetamide produced in Example 8, followed by stirring at room temperature for 20 hours. The reaction mixture was poured into water, followed by extraction with ethyl acetate. The extract solution was washed with an aqueous saturated sodium chloride solution and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (elutant:ethyl acetate/hexane=1/2) to obtain 0.12 g (yield: 29%) of a title compound.
Reaction SMILES: [C:1]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:15][C:16]([S@@:19]([NH2:21])=[O:20])([CH3:18])[CH3:17]>O1CCOCC1.[Cl-].[Na+].O>[C:2]1([C:1]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:21][S@:19]([C:16]([CH3:18])([CH3:17])[CH3:15])=[O:20])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)[S@@](N)=O
Reactant: O=C(c1ccccc1)c1ccccc1
Agent: [Cl-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: CC(C)(C)[S@](=O)N=C(c1ccccc1)c1ccccc1
Temperature: 105 °C
Reaction time: 0.17 h

Procedure:
In a flame dried flask under N2, benzophenone (0.514 g, 2.82 mmol) was dissolved in anhydrous dioxane (5 mL). Ti(IV) ethoxide (1.479 mL, 7.05 mmol) was added followed by (S)-(−)-2-methyl-2-propanesulfinamide (0.376 g, 3.10 mmol). The rxn was heated to 105° C. After 4.5 hr the reaction was cooled to RT and brine (15 mL) was added. A precipitate formed and the reaction was rapidly stirred for 10 min. The suspension was filtered through celite and the filter cake was washed with brine and ethyl acetate. The layers of the filtrate were separated. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo to afford a yellow oil. The oil was purified by flash column chromatography (90:10 hexanes/ethyl acetate). The fractions were combined and concentrated in vacuo to afford (S)-N-(diphenylmethylene)-2-methylpropane-2-sulfinamide as a light yellow oil. 1H NMR (CDCl3) δ 7.51-7.43 (broad m, 10H), 1.30 (s, 9H). [M+H]+=286.1.
Reaction SMILES: [C:1]([NH:8][CH2:9][CH2:10]OS(C)(=O)=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH3:16][NH2:17]>C1COCC1>[C:1]([NH:8][CH2:9][CH2:10][NH:17][CH3:16])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]
Reactant: CC(C)(C)OC(=O)NCCOS(C)(=O)=O
Reactant: CN
Solvent: C1CCOC1
Product: CNCCNC(=O)OC(C)(C)C
Temperature: 42.5 °C
Reaction time: 3 h
Yield: 76.3 %

Procedure:
With reference to FIG. 10c, BocNHCH2CH2OMs (32) (1.42 g, 5.94 mmol) was transferred to a Chem-Glass pressure vessel using minimum amount of THF to which 60 mL of methylamine (MeNH2, P/N: Aldrich 395056, 2.0 M in THF, 120 mmol) solution was added, capped and heated (while stirring) at 40-45° C. for 3 h, then at RT for overnight (use safety shield). TLC analysis (1:1 EtOAc-hexanes) showed complete consumption of 32 and formation of a new product (Rf 33=0.38; 1:1 DCM-MeOH+1% (v/v) Et3N; TLC plate was heated first for 5 min to remove Et3N then developed by heating with 3% (w/v) ninhydrin solution in EtOH). Reaction mixture then concentrated to an oil and purified by column chromatography (40 g SiO2 column Isco.; 40 mL/min, Column equilibrated with EtOAc, eluted with 1:1 MeOH-DCM+1% Et3N (v/v). 18 mL-fractions collected; fractions 13-19 had pure product) to give BocNH13CH213CH2NHMe 33 as colorless oil (0.79 g, 76%).). ES-MS (Direct infusion in MeOH) Calculated MH+ [13C2C6H18N2O2+H]+=177.14, observed MH+=177.14.
Reaction SMILES: [ClH:1].[CH3:2][NH:3][CH2:4][C:5]#[N:6].[C:7]([Cl:12])(=O)[C:8](Cl)=[O:9]>ClC1C=CC=CC=1Cl>[Cl:12][C:7]1[C:8](=[O:9])[N:3]([CH3:2])[CH:4]=[C:5]([Cl:1])[N:6]=1
Reactant: O=C(Cl)C(=O)Cl
Reactant: Cl
Reactant: CNCC#N
Solvent: Clc1ccccc1Cl
Product: Cn1cc(Cl)nc(Cl)c1=O
Temperature: 80 °C
Yield: 60.8 %

Procedure:
3.29 g (30.8 mmoles) of methylamino-acetonitrile hydrochloride is placed in the presence of 19.6 g (154 mmoles) of oxalyl chloride in 30 ml of 1,2-dichlorobenzene. The mixture is heated for 8 hours at 80° C. After concentrating the reaction medium to dryness, the residue obtained is purified by flash chromatography (Petroleum ether-CH2Cl2 gradient 100-0 to 0-100). 3.35 g of intermediate 4c is obtained in beige powder form (yield: 60%).
Reaction SMILES: [OH:1][C:2]1[C@@:6]([CH3:13])([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[NH:5][C:4](=[O:14])[CH:3]=1.[CH:15](=O)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[F:23][C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[NH:29][CH:28]=[C:27]2[CH3:33]>>[F:23][C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[NH:29][C:28]([CH:15]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:3]1[C:4](=[O:14])[NH:5][C@:6]([CH3:13])([C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)[C:2]=1[OH:1])=[C:27]2[CH3:33]
Reactant: C[C@]1(c2ccccc2)NC(=O)C=C1O
Reactant: O=Cc1ccccc1
Reactant: Cc1c[nH]c2ccc(F)cc12
Product: Cc1c(C(C2=C(O)[C@@](C)(c3ccccc3)NC2=O)c2ccccc2)[nH]c2ccc(F)cc12

Procedure:
Using general procedure D, (R)-4-hydroxy-5-methyl-5-phenyl-1,5-dihydro-pyrrol-2-one (prepared according to Lit. 11, see also Lit. 19) was reacted with benzaldehyde and 5-fluoro-3-methyl-1H-indole to give the title compound as a pale yellow foam. MS: 425.4 ([M−H]−).
Reaction SMILES: Cl[CH2:2][C:3]1[N:4]=[C:5]([CH:8]=[CH:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=2)[O:6][CH:7]=1.[N:20]1([CH2:25][CH2:26][CH2:27][CH2:28][C:29]2[N:34]=[CH:33][C:32]([OH:35])=[CH:31][N:30]=2)[CH:24]=[CH:23][N:22]=[N:21]1.C(=O)([O-])[O-].[Cs+].[Cs+].C(OCC)(=O)C>CN(C=O)C>[N:20]1([CH2:25][CH2:26][CH2:27][CH2:28][C:29]2[N:34]=[CH:33][C:32]([O:35][CH2:2][C:3]3[N:4]=[C:5]([CH:8]=[CH:9][C:10]4[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=4)[O:6][CH:7]=3)=[CH:31][N:30]=2)[CH:24]=[CH:23][N:22]=[N:21]1
Reactant: Oc1cnc(CCCCn2ccnn2)nc1
Reactant: FC(F)(F)c1ccc(C=Cc2nc(CCl)co2)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: FC(F)(F)c1ccc(C=Cc2nc(COc3cnc(CCCCn4ccnn4)nc3)co2)cc1
Reaction time: 2 h

Procedure:
A mixture of 4-chlormethyl-2-[2-(4-trifluoromethyl-phenyl)-vinyl]-oxazole (0.144 g, 0.50 mmol), 2-(4-[1,2,3]triazol-1-yl-butyl)-pyrimidin-5-ol (0.078 g, 0.357 mmol) and cesium carbonate (Cs2CO3) (0.175 g, 0.536 mmol) in DMF (10 ml) is kept at 80° C. for 2 h. After cooling ethyl acetate (25 ml) is added, the mixture is washed with sat. NH4Cl and brine, dried over MgSO4 and concentrated in vacuo. The crude product is purified by flash column chromatography (ethyl acetate (100%)->ethyl acetate/methanol 9:1) and 2-(4-[1,2,3]-triazol-1-yl-butyl)-5-{2-[2-(4-trifluoromethyl-phenyl)-vinyl]-oxazol-4-ylmethoxy}-pyrimidine can be isolated as a white solid. Yield 40 mg (24%).