Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([C:4]2[CH:5]=[C:6]3[C:10](=[C:11]([CH:13]([O:15][CH2:16][C:17]4([C:23]5[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=5)[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]4)[CH3:14])[CH:12]=2)[NH:9][N:8]=[CH:7]3)[CH2:3][CH2:2]1.[C:30]([BH3-])#N.[Na+].C=O.C(O)(=O)C>C(#N)C.C(O)(=O)C>[CH:1]1([C:4]2[CH:5]=[C:6]3[C:10](=[C:11]([CH:13]([O:15][CH2:16][C:17]4([C:23]5[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=5)[CH2:22][CH2:21][N:20]([CH3:30])[CH2:19][CH2:18]4)[CH3:14])[CH:12]=2)[NH:9][N:8]=[CH:7]3)[CH2:3][CH2:2]1
Reactant: CC(OCC1(c2ccc(F)cc2)CCNCC1)c1cc(C2CC2)cc2cn[nH]c12
Reactant: [BH3-]C#N
Agent: C=O
Agent: [Na+]
Solvent: CC#N
Solvent: CC(=O)O
Product: CC(OCC1(c2ccc(F)cc2)CCN(C)CC1)c1cc(C2CC2)cc2cn[nH]c12
Reaction time: 0.08 h

Procedure:
To a suspension of (±)-5-cyclopropyl-7-(1-((4-(4-fluorophenyl)piperidin-4-yl)methoxy)ethyl)-1H-indazole (13.5 mg, 0.036 mmol) and sodium cyanoborohydride (11.2 mg, 0.178 mmol) in acetonitrile (1 mL) at 0° C. was added formalin (0.027 mL). The reaction was treated with 1 drop of acetic acid. After 5 min, a second drop of acetic acid was added and the ice bath was removed, stirring continued for another hour. The reaction was diluted with diethyl ether and washed with 1 M sodium hydroxide. The ethereal was concentrated and loaded onto a strong cation exchange cartridge in methanol. The cartridge was flushed with several volumes of methanol which were discarded. The product was eluted with 2 M ammonia in methanol and concentrated. It was then purified by column chromatography (10% 2 M ammonia in MeOH/CH2Cl2) to give 10.5 mg (46.5%) as clear oil. 1H-NMR (CDCl3, 500 MHz) δ 9.63 (bs, 1H), 7.86 (s, 1H), 7.23-7.27 (m, 3H), 7.03-7.07 (m, 2H), 6.78 (s, 1H), 4.47 (q, J=5.0 Hz, 1H), 3.35 (d, J=10 Hz, 1H), 3.24 (d, J=5 Hz, 1H), 2.55-2.70 (m, 2H), 1.91-2.30 (m, 9H), 1.40 (d, J=10.0 Hz, 3H), 0.9-0.94 (m, 2H), 0.62-0.68 (m, 2H); 13C-NMR (CDCl3, 126 MHz) δ 161.5 (d, J=978 Hz), 136.2, 135.9, 133.9, 128.8, 125.9, 124.3, 123.3, 115.8, 115.6, 115.4, 78.9, 51.9, 51.7, 46.1, 40.3, 32.4, 32.3, 22.4, 15.4, 8.7; Mass spec.: 408.09 (MH)+.
Reaction SMILES: [CH3:1][N:2]([CH3:17])[CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9](B(O)O)=[CH:8][C:7]=1[CH:15]=[O:16].Br[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1>>[CH3:1][N:2]([CH3:17])[CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=2)=[CH:8][C:7]=1[CH:15]=[O:16]
Reactant: Brc1ccccn1
Reactant: CN(C)CCOc1ccc(B(O)O)cc1C=O
Product: CN(C)CCOc1ccc(-c2ccccn2)cc1C=O
Yield: 40 %

Procedure:
General procedure G using 4-(2-dimethylamino-ethoxy)-3-formyl-benzeneboronic acid and 2-bromo-pyridine gave the title product as yellow oil in 40% yield. 1H-NMR (CDCl3) δ 10.47 (s, 1H), 8.60(dt, 1H), 8.34 (d, 1H), 8.26 (dd, 1H), 7.69-7.67 (m, 2H), 7.17-7.14 (m, 1H), 7.05 (d, 1H), 4.24 (t, 2H), 2.83 (t, 2H), 2.36 (s, 6H).
Reaction SMILES: C[O:2][C:3]1[CH:12]=[C:11]2[C:6]([C@H:7]([C:23]3[CH:28]=[CH:27][C:26]([O:29][CH2:30][CH2:31][N:32]4[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]4)=[CH:25][CH:24]=3)[C@H:8]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=3)[CH2:9][O:10]2)=[CH:5][CH:4]=1.Cl.N1C=CC=CC=1>>[OH:2][C:3]1[CH:12]=[C:11]2[C:6]([C@H:7]([C:23]3[CH:28]=[CH:27][C:26]([O:29][CH2:30][CH2:31][N:32]4[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37]4)=[CH:25][CH:24]=3)[C@H:8]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:20])([F:21])[F:22])[CH:14]=3)[CH2:9][O:10]2)=[CH:5][CH:4]=1
Reactant: COc1ccc2c(c1)OC[C@@H](c1cccc(C(F)(F)F)c1)[C@H]2c1ccc(OCCN2CCCCC2)cc1
Agent: Cl
Solvent: c1ccncc1
Product: Oc1ccc2c(c1)OC[C@@H](c1cccc(C(F)(F)F)c1)[C@H]2c1ccc(OCCN2CCCCC2)cc1

Procedure:
In an manner analogous to that described in step 5 for Example 10, (±)-cis-7-methoxy-4-(4-(2-piperidinoethoxy)phenyl)-3-(3-(trifluoromethyl)phenyl)chromane (0.256 g, 0.50 mmol) was de-methylated by heating with pyridine hydrochloride to give the title compound as an off-white solid.
Reaction SMILES: [N+:1]([C:4]1[CH:11]=[CH:10][C:7]([CH2:8]Cl)=[CH:6][CH:5]=1)([O-:3])=[O:2].[NH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1.O>C1COCC1>[N+:1]([C:4]1[CH:11]=[CH:10][C:7]([CH2:8][N:12]2[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]2)=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1ccc(CCl)cc1
Reactant: C1CCNCC1
Solvent: C1CCOC1
Solvent: O
Product: O=[N+]([O-])c1ccc(CN2CCCCC2)cc1
Temperature: 25 °C
Reaction time: 20 h
Yield: 99.9 %

Procedure:
In THF (50 ml) was dissolved 4-nitrobenzylchloride (5.00 g), and piperidine (6.20 g) was added to the mixture. The reaction mixture was stirred at room temperature for 20 hours. To the mixture was added water (500 ml), and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with anhydrous sodium sulfate and concentrated under reduced pressure. The residue was separated and purified with column chromatography (ethyl acetate/hexane=1/2) to give 1-(4-nitrobenzyl)piperidine (6.41 g) as pale yellow oil. 1H NMR (200 MHz, CDCl3) δ: 1.38-1.70 (6H, m), 2.30-2.45 (4H, m), 3.55 (2H, s), 7.51 (2H, d, J=8.8 Hz), 8.17 (2H, d, J=8.8 Hz).
Reaction SMILES: [CH3:1][C:2]1([CH3:25])[C:6]2[C:7]([O:11][C:12]3[N:17]=[CH:16][C:15]([NH:18][C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[NH2:21])=[CH:14][N:13]=3)=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3]1.Cl[C:27](Cl)([O:29]C(=O)OC(Cl)(Cl)Cl)Cl>ClCCl>[CH3:1][C:2]1([CH3:25])[C:6]2[C:7]([O:11][C:12]3[N:17]=[CH:16][C:15]([N:18]4[C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[NH:21][C:27]4=[O:29])=[CH:14][N:13]=3)=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3]1
Reactant: CC(C)(N)C(=O)Nc1cnc(Oc2cccc3c2C(C)(C)CO3)nc1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: ClCCl
Product: CC1(C)NC(=O)N(c2cnc(Oc3cccc4c3C(C)(C)CO4)nc2)C1=O
Temperature: 0 °C
Reaction time: 2 h
Yield: 147 %

Procedure:
To a solution of N1-{2-[(3,3-dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-5-pyrimidinyl}-2-methylalaninamide (Intermediate 143, 18 mg, 0.053 mmol) in dry Dichloromethane (DCM) (3 mL) TEA (0.037 ml, 0.263 mmol) was added and the reaction mixture was cooled to 0° C. A solution of triphosgene (7.02 mg, 0.024 mmol) in dry Dichloromethane (1 mL) was slowly added and the reaction mixture was stirred for 2 hours while the temperature was allowed to reach r.t. The reaction was quenched with water (3 ml) and two phases were separated. The organic layer was dried (Na2SO4), filtered and evaporated and the residue was purified by flash chromatography (Biotage system) on silica gel using a column SNAP 10 g and cyclohexane/ethyl acetate from 8:2 to 1:1 as eluents affording the title compound (13 mg) as a white solid.
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[N+:9]([O-])=O>CO.[Ni]>[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[NH2:9]
Reactant: O=[N+]([O-])c1cccc(Cl)c1Cl
Agent: [Ni]
Solvent: CO
Product: Nc1cccc(Cl)c1Cl
Reaction time: 3.5 h

Procedure:
2,3-Dichloronitrobenzene (800 g, 4.17 moles) was dissolved in methanol (5.6 L) and charged into an autoclave. Raney nickel (80 g, 10% w/w) was added to the solution. The reaction mixture was hydrogenated at 80 psi for 3.5 hrs at 30° C. and filtered through celite. Methanol was distilled off to give 2,3-dichloroaniline (C6H3Cl2NH2).
Reaction SMILES: CS(Cl)(=O)=O.[CH2:6]([C:13]1[C:18]([O:19][CH2:20][O:21][CH3:22])=[CH:17][CH:16]=[C:15]([C:23]2(O)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[N:14]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C(N(CC)CC)C.ClCCl>C(OCC)(=O)C.O>[CH2:6]([C:13]1[C:18]([O:19][CH2:20][O:21][CH3:22])=[CH:17][CH:16]=[C:15]([C:23]2[CH2:28][CH2:27][O:26][CH2:25][CH:24]=2)[N:14]=1)[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1
Reactant: COCOc1ccc(C2(O)CCOCC2)nc1Cc1ccccc1
Agent: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: O
Solvent: ClCCl
Product: COCOc1ccc(C2=CCOCC2)nc1Cc1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 36.8 %

Procedure:
716 μl of methanesulfonyl chloride was added dropwise into a mixture of 1.02 g of 2-benzyl-6-(4-hydroxytetrahydro-4H-pyran-4-yl)-3-methoxymethyloxypyridine (Example 60a), 1.72 ml of triethylamine and 10 ml of dichloromethane under ice-cooling. After stirring at room temperature overnight, water and ethyl acetate were added thereto. The organic phase was washed with water and brine, dried over anhydrous magnesium sulfate and the solvent was removed. The residue was subjected to silica gel column chromatography using 20% ethyl acetate/hexane, to give 355 mg of the target compound.
Reaction SMILES: [Cl:1][C:2]([C:12]([F:15])([F:14])[F:13])=[CH:3][C@H:4]1[C@H:6]([C:7](O)=[O:8])[C:5]1([CH3:11])[CH3:10].N1C=CC=CC=1.S(Cl)([Cl:24])=O>C1(C)C=CC=CC=1>[Cl:1][C:2]([C:12]([F:15])([F:14])[F:13])=[CH:3][C@H:4]1[C@H:6]([C:7]([Cl:24])=[O:8])[C:5]1([CH3:11])[CH3:10]
Reactant: CC1(C)[C@@H](C=C(Cl)C(F)(F)F)[C@@H]1C(=O)O
Reactant: O=S(Cl)Cl
Solvent: c1ccncc1
Solvent: Cc1ccccc1
Product: CC1(C)[C@@H](C=C(Cl)C(F)(F)F)[C@@H]1C(=O)Cl
Temperature: 25 °C
Reaction time: 17 h
Yield: 84.1 %

Procedure:
To a stirred solution of 4.1 g (0.0173 mole) of trans-3-(2-chloro-3,3,3-trifluoro-1-propenyl)-2,2-dimethylcyclopropanecarboxylic acid in 40 mL of toluene at ambient temperature was added 1.7 g (0.022 mole) of pyridine, then 2.6 g (0.022 mole) of thionyl chloride in 25 mL of toluene. Upon complete addition the reaction mixture was stirred at ambient temperature for 17 hours. The reaction mixture was filtered through diatomaceous earth, and the filtrate was evaporated under reduced pressure to give 3.8 g of trans-3-(2-chloro-3,3,3-trifluoro-1-propenyl)-2,2-dimethylcyclopropanecarbonyl chloride.
Reaction SMILES: N([CH2:4][C:5]1[O:9][C:8]([C:10]2[CH:15]=[CH:14][C:13]([C:16]3[C:21]([CH3:22])=[CH:20][CH:19]=[C:18]([C:23]([NH:25][CH:26]4[CH2:28][CH2:27]4)=[O:24])[CH:17]=3)=[CH:12][CH:11]=2)=[N:7][N:6]=1)=[N+]=[N-].C(N(CC)CC)C.Cl.[CH:37]1(CC(=N)OCC)[CH2:39][CH2:38]1>C(O)C>[CH:26]1([NH:25][C:23]([C:18]2[CH:17]=[C:16]([C:13]3[CH:12]=[CH:11][C:10]([C:8]4[O:9][C:5]([CH2:4][CH:37]5[CH2:39][CH2:38]5)=[N:6][N:7]=4)=[CH:15][CH:14]=3)[C:21]([CH3:22])=[CH:20][CH:19]=2)=[O:24])[CH2:28][CH2:27]1
Reactant: CCOC(=N)CC1CC1
Reactant: Cc1ccc(C(=O)NC2CC2)cc1-c1ccc(-c2nnc(CN=[N+]=[N-])o2)cc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCO
Product: Cc1ccc(C(=O)NC2CC2)cc1-c1ccc(-c2nnc(CC3CC3)o2)cc1

Procedure:
4′-[5-(Azidomethyl)-1,3,4-oxadiazol-2-yl]-N-cyclopropyl-6-methyl-1,1′-biphenyl-3-carboxamide (Intermediate 44) (40 mg), triethylamine (0.051 ml) and ethyl 2-cyclopropylethanimidate hydrochloride (23 mg) in ethanol (3 ml) were heated at 80° C. for 16 hours. The ethanol was removed under vacuum, the residue applied to a bond-elut (silica) and eluted with an ethyl acetate/cyclohexane gradient. Evaporation of the solvent from the product fractions gave N-cyclopropyl-4′-[5-(cyclopropylmethyl)-1,3,4-oxadiazol-2-yl]-6-methyl-1,1′-biphenyl-3-carboxamide.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH:15]2[CH:11]([N:12]([C:19]([O:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[O:20])[CH2:13][CH:14]2[C:16]([OH:18])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[NH2:60][C:61]1[C:70]2[C:65](=[CH:66][CH:67]=[CH:68][CH:69]=2)[CH:64]=[CH:63][CH:62]=1>CN1C(=O)CCC1.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH:15]2[CH:11]([N:12]([C:19]([O:21][CH2:22][C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)=[O:20])[CH2:13][CH:14]2[C:16](=[O:18])[NH:60][C:61]2[C:70]3[C:65](=[CH:66][CH:67]=[CH:68][CH:69]=3)[CH:64]=[CH:63][CH:62]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(C)(C)OC(=O)N1CCC2C1C(C(=O)O)CN2C(=O)OCc1ccccc1
Reactant: Nc1cccc2ccccc12
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN1CCOCC1
Solvent: CN1CCCC1=O
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N1CCC2C1C(C(=O)Nc1cccc3ccccc13)CN2C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 95 %

Procedure:
A solution of 36 (390 mg, 1.00 mmol) in NMP (5 mL) was cooled to 0° C. and treated with HATU (420 mg, 1.10 mmol) and NMM (0.17 mL, 1.50 mmol) followed in 15 min by the addition of 1-aminonaphthalene (145 mg, 1.00 mmol). The reaction mixture was allowed to warm to ambient temperature. After 3 h, the solution was diluted with EtOAc, washed with H2O, 1M HCl, H2O, sat NaHCO3, brine, dried over anhydrous Na2SO4, filtered and concentrated. Purification by reverse phase HPLC (2″ Dynamax® C18, 10-70% ACN in H2O with 0.1% HOAc over 30 min) afforded 53 (490 mg) as a white foam. 1H NMR (CDCl3, 300 MHz), ˜2:1 mixture of rotomers: δ8.32 (d, J=8.4 Hz, 1H), 8.15 (d, J=7.80 Hz, 1H), 7.84 (m, 1H), 7.64 (d, J=8.40 Hz, 1H), 7.42-7.56 (m, 4H), 7.26-7.42 (m, 4H), 5.17 (br s, 2H), 4.62 (m, 2H), 4.48 (dd, J=11.6, 2.5 Hz, 1H), 3.30-3.70 (m, 5H), 2.0-2.20 (m, 2H), 1.55 (s, 9H) ppm. Mass spectrum, m/z [516.1] (M+H)+.
Reaction SMILES: C([O:3][C:4]([CH:6]1[CH2:11][CH2:10][CH2:9][CH2:8][CH:7]1[N:12]([CH:33]1[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1)[C:13](=[O:32])[CH2:14][C:15]1[NH:20][C:19]2[CH:21]=[CH:22][C:23]([NH:25][S:26]([CH3:29])(=[O:28])=[O:27])=[CH:24][C:18]=2[S:17](=[O:31])(=[O:30])[N:16]=1)=O)C.[O-]CC.[Na+].Cl>C(O)C>[CH:33]1([N:12]2[CH:7]3[CH:6]([CH2:11][CH2:10][CH2:9][CH2:8]3)[C:4]([OH:3])=[C:14]([C:15]3[NH:20][C:19]4[CH:21]=[CH:22][C:23]([NH:25][S:26]([CH3:29])(=[O:27])=[O:28])=[CH:24][C:18]=4[S:17](=[O:31])(=[O:30])[N:16]=3)[C:13]2=[O:32])[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38]1
Reactant: CCOC(=O)C1CCCCC1N(C(=O)CC1=NS(=O)(=O)c2cc(NS(C)(=O)=O)ccc2N1)C1CCCCC1
Agent: CC[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Product: CS(=O)(=O)Nc1ccc2c(c1)S(=O)(=O)N=C(C1=C(O)C3CCCCC3N(C3CCCCC3)C1=O)N2
Temperature: 60 °C
Reaction time: 4 h
Yield: 41.4 %

Procedure:
2-{Cyclohexyl-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cyclohexanecarboxylic acid ethyl ester (0.48 g, 0.845 mmol) was dissolved in ethanol (15 mL), a 21% w/w solution of sodium ethoxide in ethanol (1.095 g, 3.38 mmol) was added. The mixture was stirred at 60° C. for 4 h and allowed to cool to 25° C. The mixture was poured into a 1.0 M aqueous hydrochloric acid solution (50 mL). The product started to precipitate and was collected by vacuum filtration. The precipitate was washed with water and dried under high vacuum to afford the pure product, N-[3-(1-cyclohexyl-4-hydroxy-2-oxo-1,2,4a,5,6,7,8,8a-octahydro-quinolin-3-yl)-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl]-methanesulfonamide (0.183 g, 0.35 mmol, 41.4%), as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ: 1.07-1.89 (18H, m), 2.32 (1H, bs), 3.05 (3H, s), 3.61-4.33 (3H, m), 7.47-7.60 (3H, m), 7.49-7.57 (3H, m), 10.15 (1H, s), 13.88 (1H, s). LC-MS (ESI) calcd for C23H30N4O6S2 522.16, found 523.4 [M+H+].
Reaction SMILES: [CH3:1][O:2][C:3](=[O:17])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][CH:10]=1.C(O)(=[O:20])C>O.C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:17])[CH2:4][CH2:5][CH2:6][CH2:7][C:8](=[O:20])[C:9]1[CH:10]=[CH:11][C:12]([C:15]#[N:16])=[CH:13][CH:14]=1
Reactant: CC(=O)O
Reactant: COC(=O)CCCCCc1ccc(C#N)cc1
Solvent: CCOC(C)=O
Solvent: O
Product: COC(=O)CCCCC(=O)c1ccc(C#N)cc1
Temperature: 25 °C
Reaction time: 17.5 h
Yield: 11 %

Procedure:
The compound (620 mg) obtained in the above (1) is dissolved in a mixture of acetic acid (30 ml) and water (5 ml), and thereto is added chromic anhydride (1.3 g)/acetic acid (2 ml), and the mixture is stirred at room temperature for 17.5 hours. The mixture is diluted with ethyl acetate, and washed with a saturated aqueous sodium hydrogen carbonate solution, and purified by silica gel column chromatography (n-hexane/ethyl acetate=5:1→2:1) to give the title compound (70 mg, 11%), and the starting compound (365 mg, 59%) is also recovered.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@H:8]1[CH2:12][O:11][C:10](=[O:13])[NH:9]1.[H-].[Na+].[Br:16][C:17]1[CH:18]=[N:19][N:20]2[CH:25]=[CH:24][C:23](Cl)=[N:22][C:21]=12.[Cl-].[NH4+]>CN(C=O)C>[Br:16][C:17]1[CH:18]=[N:19][N:20]2[CH:25]=[CH:24][C:23]([N:9]3[C@@H:8]([C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=4[Cl:1])[CH2:12][O:11][C:10]3=[O:13])=[N:22][C:21]=12
Reactant: Clc1ccn2ncc(Br)c2n1
Reactant: O=C1N[C@@H](c2ccccc2Cl)CO1
Agent: [Cl-]
Agent: [H-]
Agent: [NH4+]
Solvent: CN(C)C=O
Product: O=C1OC[C@H](c2ccccc2Cl)N1c1ccn2ncc(Br)c2n1
Temperature: 25 °C
Reaction time: 1 h
Yield: 34.1 %

Procedure:
To (S)-4-(2-chlorophenyl)oxazolidin-2-one (265 mg, 1.34 mmol) in DMF (10 mL) was added sodium hydride (59.0 mg, 1.48 mmol) and the reaction was stirred at ambient temperature for 1 hour. 3-Bromo-5-chloropyrazolo[1,5-a]pyrimidine (343 mg, 1.48 mmol) was added in one portion and the reaction was stirred at ambient temperature for 18 hours. Ice was added followed by ammonium chloride (aqueous) and the resulting suspension was filtered and washed with water. After drying, (S)-3-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-chlorophenyl)oxazolidin-2-one (180 mg, 34.1% yield) was isolated as a pale yellow solid.
Reaction SMILES: [CH2:1](Cl)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:9]1([CH3:16])[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[CH:10]=1>>[CH3:16][C:9]1[CH:14]=[CH:13][C:12]([CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[C:11]([CH3:15])[CH:10]=1
Reactant: Cc1cccc(C)c1
Reactant: ClCc1ccccc1
Product: Cc1ccc(Cc2ccccc2)c(C)c1

Procedure:
To 100 g of 2,4-dimethyldiphenylmethane obtained by the reaction between meta-xylene and benzyl chloride, having the following formula (b.p. 295°-296° C/760 mmHg, specific gravity (D420) 0.9951); ##STR3## was dissolved 3 g of crystal violet lactone. The resulting solution was then added to a solution of 20 g of gum arabic and 160 g of water to emulsify. Thereafter, 20 g of acid processed gelatin and 160 g of water were added thereto and the pH thereof was reduced to 5 by the addition of acetic acid under constant stirring. 500 g of water was then added to cause coacervation. On coacervation, a dense liquid membrane of gelatin-gum arabic was formed around the oil droplets containing a color former. The pH was further reduced to 4.4, and 4 g of 37 percent formation was successively added for hardening the membrane. Said operation was carried out keeping the temperature of the system at a temperature of 50° C. Then the system was cooled to 10° C in order to gel the dense liquid membrane. Furthermore, in order to raise the effect of hardening, the pH thereof was raised to 9 and the system was allowed to stand for several hours to accomplish the encapsulation. The capsule solution thus obtained was coated on a sheet of paper by air knife coating, then dried. The pressure sensitive recording paper thus obtained had no unpleasant smell like that of the conventional pressure sensitive recording paper wherein chlorinated diphenyl was used as a solvent. When this paper (upper paper) was superposed on a clay paper (aforesaid lower paper coated with active clay substance) and writing was conducted with pressure, there was developed a blue image on a clayed paper in an instant. The density of this color developed image was remarkably high compared with that of the conventional pressure sensitive recording paper. In addition, even when this upper paper was exposed to sun light for a long time, the lowering in the color developing ability and colored fog were not recognized.
Reaction SMILES: [CH:1](=[O:9])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4].N1C=CC=CC=1.[Br:16][CH2:17][C:18](Br)=[O:19]>ClCCl>[CH:1]([C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[O:4][C:18](=[O:19])[CH2:17][Br:16])=[O:9]
Reactant: O=C(Br)CBr
Reactant: O=Cc1ccccc1O
Solvent: ClCCl
Solvent: c1ccncc1
Product: O=Cc1ccccc1OC(=O)CBr
Reaction time: 1 h
Yield: 60.3 %

Procedure:
To a solution of Salicylaldehyde (50 grams) and pyridine (48.5 grams) in dichloromethane (500 ml) maintained at 0-5° C. under nitrogen atmosphere was added dropwise bromoacetyl bromide (210.6 grams). The reaction mixture was stirred for one hour at the same temperature. The reaction mixture was washed with 1000 ml of water and 1500 ml of 5% sodium bicarbonate solution, dried over sodium sulphate followed by distillation of solvent under reduced pressure to get 60.0 grams of bromo-acetic acid 2-formyl-phenyl ester.
Reaction SMILES: [C:1]([O:5][C:6](=[O:15])[CH:7]([O:11][C:12](=[O:14])[CH3:13])[C:8]([CH3:10])=[O:9])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH2:18](Br)[CH2:19][CH2:20][CH2:21][CH2:22][CH3:23]>CN(C=O)C>[C:1]([O:5][C:6](=[O:15])[C:7]([O:11][C:12](=[O:14])[CH3:13])([C:8](=[O:9])[CH3:10])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])([CH3:2])([CH3:3])[CH3:4]
Reactant: CCCCCCBr
Reactant: CC(=O)OC(C(C)=O)C(=O)OC(C)(C)C
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCCCCCC(OC(C)=O)(C(C)=O)C(=O)OC(C)(C)C
Yield: 70.8 %

Procedure:
According to the general alkylation method, tert-butyl-2-acetoxy-aceto-acetate (219a) (1.08 g, 5.00 mmol), NaH (156 mg, 6.5 mmol) and hexylbromide (702 μL, 825 mg, 5.00 mmol) were reacted in DMF (10 mL) to give 2-acetoxy-2-acetyl-octanoic-acid-tert-butylester (250k) (1063 mg, 3.54 mmol, 71%) as a slightly yellow oil. Then, 250k (2.19 g, 7.29 mmol) and 139 mg (0.73 mmol) p-TsOH.H2O were stirred in 22.0 mL benzene according to decarboxylation method A. Kugelrohr distillation at 0.8 mbar and 80° C. and subsequent flash-chromatography (column dimensions: 2.0×20.0 cm, diethylether/petroleum ether=1:6) gave 251k (419 mg 2.10 mmol, 29%) as a colorless oil.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@@H:9]1[C:14]([OH:16])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.ClC(OCC(C)C)=O.C[Si]([CH:38]=[N+:39]=[N-:40])(C)C>O1CCCC1.C(#N)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[C:14](=[O:16])[CH:38]=[N+:39]=[N-:40])=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: C[Si](C)(C)C=[N+]=[N-]
Reactant: CC(C)(C)OC(=O)N1CCCC[C@@H]1C(=O)O
Agent: CC(C)COC(=O)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCCCC1C(=O)C=[N+]=[N-]
Temperature: 0 °C
Reaction time: 4 h
Yield: 23.3 %

Procedure:
A solution of (R)-(+)-piperidine-1,2-dicarboxylic acid 1-tert-butyl ester (1.00 g, 4.4 mmol) in dry tetrahydrofuran (9.6 mL) was cooled to 0° C. and treated with diisopropylethylamine (0.95 g, 1.3 mL) and isobutyl chloroformate (0.89 g, 0.86 mL, 6.5 mmol). A white suspension formed, which was stirred at 0° C. for 4 h. The mixture was then diluted with acetonitrile (6.6 mL) until a clear solution was obtained. A cooled (0° C.) solution of trimethylsilyl diazomethane (2N in hexanes, 4.4 mL, 8.7 mmol) in dry tetrahydrofuran (3 mL) and acetonitrile (3 mL) was added to the reaction mixture during 3 min. The mixture was then stirred at 0° C. for 3 h, and at room temperature for 16 h. The volatiles were evaporated and the residue purified by flash chromatography (heptane/ethyl acetate gradient) to yield 2-(2-diazo-acetyl)-piperidine-1-carboxylic acid tert-butyl ester as a yellow oil (0.26 g, 23%), MS (ISP): 254.14 (M+H)+..