Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH-].[K+].[C:3]([O:7][C:8]([C@@H:10]1[CH2:14][S:13][C@H:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[F:21])[N:11]1[C:22](=[O:39])[CH2:23][NH:24][C:25](=[O:38])[NH:26][C:27]1[CH:28]=[C:29]([CH2:33][C:34]([O:36]C)=[O:35])[CH:30]=[CH:31][CH:32]=1)=[O:9])([CH3:6])([CH3:5])[CH3:4]>O.CO.O.[OH-].[Na+]>[C:3]([O:7][C:8]([C@@H:10]1[CH2:14][S:13][C@H:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[F:21])[N:11]1[C:22](=[O:39])[CH2:23][NH:24][C:25](=[O:38])[NH:26][C:27]1[CH:28]=[C:29]([CH2:33][C:34]([OH:36])=[O:35])[CH:30]=[CH:31][CH:32]=1)=[O:9])([CH3:6])([CH3:4])[CH3:5]
Reactant: COC(=O)Cc1cccc(NC(=O)NCC(=O)N2[C@@H](c3ccccc3F)SC[C@H]2C(=O)OC(C)(C)C)c1
Agent: [K+]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CC(C)(C)OC(=O)[C@@H]1CS[C@H](c2ccccc2F)N1C(=O)CNC(=O)Nc1cccc(CC(=O)O)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 28.1 %

Procedure:
At a temperature in the vicinity of 25° C., 0.12 g of potassium hydroxide is added to a solution of 0.95 g of methyl (2R,4R)-3-{3-{2-[4-tert-butoxycarbonyl-2-(2-fluorophenyl)-3-thiazolidinyl]-2-oxoethyl}ureido}phenylacetate in 6 cm3 of a water/methanol (30/70 by volume) mixture. The reaction mixture is stirred for 3 hours at a temperature in the vicinity of 25° C. then concentrated to about half under reduced pressure. The solution obtained is diluted with 40 cm3 of water, washed with 2 times 30 cm3 of ethyl ether, then brought to a pH of 2 by addition of 2.1 cm3 of a 1N aqueous sulphuric acid solution. The insoluble product is separated by filtration and purified by chromatography on silica [eluent: ethyl acetate/methanol (90/10 by volume)]. The fractions containing the expected product are combined and concentrated to dryness under reduced pressure at 40° C. The amorphous product thus obtained (0.26 g) is dissolved in a 1N aqueous sodium hydroxide solution. This solution is filtered, then acidified by addition of a 1N aqueous sulphuric acid solution. The product thus precipitated is separated by filtration, washed with 3 times 10 cm3 of water, then dried in air. 0.26 g of (2R,4R)-3-{3-{2-[4-tert-butoxycarbonyl-2-(2-fluorophenyl)-3-thiazolidinyl]-2-oxoethyl}ureido}phenylacetic acid, melting at 110° C., is thus obtained ([α]D20 =+51.1°±1.6° (C=0.528%; DMF), [proton NMR (200 MHz, DMSO D6 plus several drops of CD3COOD, δ in ppm, J in Hz), 2 rotamers at room temperature, peak coalescence at 120° C., characteristic chemical shifts at 120° C.: 1.55 (s, 9H, --C(CH3)3); 3.34 and 3.52 (2dd, J=12.5 and 6.5, 2H, S--CH2 --); 3.51 (s, 2H, ArCH2COO--); 3.8 and 4.07 (2d, J=17.5, 2H, N--COCH2 --N); 5.02 (t, J=6.5, N--CH--COO); 6.55 (s, 1H, S--CH--N); 6.85 (bd, J=8, 1H, in position 4 on CO--NH--Ph); 7.05 to 7.4 (m, 6H, aromatic); 7.93 (bt, J=8.5, 1H, in position 6 on S--CH--Ph--)], [infrared spectrum (KBr), characteristic bands in cm-1 : 3380, 2980, 2930, 2700 to 2250 (broad band), 1735, 1610, 1615, 1595, 1560, 1490, 1460, 1370, 1230, 1155, 760, 705].
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[C:10]1[S:11][C:12]2[C:17]([N:18]=1)=[CH:16][CH:15]=[C:14]([C:19]1([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:21][CH2:20]1)[N:13]=2)[CH:5]=O.Cl.[NH2:29][C:30]1([C:33]([O:35][CH3:36])=[O:34])[CH2:32][CH2:31]1>>[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[C:10]1[S:11][C:12]2[C:17]([N:18]=1)=[CH:16][CH:15]=[C:14]([C:19]1([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH2:20][CH2:21]1)[N:13]=2)[CH2:5][NH:29][C:30]1([C:33]([O:35][CH3:36])=[O:34])[CH2:32][CH2:31]1
Reactant: O=Cc1ccc(-c2nc3ccc(C4(c5ccccc5)CC4)nc3s2)c(F)c1
Reactant: COC(=O)C1(N)CC1
Agent: Cl
Product: COC(=O)C1(NCc2ccc(-c3nc4ccc(C5(c6ccccc6)CC5)nc4s3)c(F)c2)CC1

Procedure:
Reaction of 3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)benzaldehyde (98.0 mg, 0.262 mmol) and methyl 1-aminocyclopropanecarboxylate hydrochloride (40 mg, 0.262 mmol) according to Reference R and the general procedure for reductive amination to give methyl 1-(3-fluoro-4-(5-(1-phenylcyclopropyl)-thiazolo[5,4-b]pyridin-2-yl)benzylamino)-cyclopropanecarboxylate as a tan solid. MS (ESI) m/z: Calculated: 473.2; Observed: 474.1 (M++1).
Reaction SMILES: [Cl:1][C:2]1[S:6][C:5]([C:7]([OH:9])=O)=[CH:4][CH:3]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[NH2:37][CH2:38][C:39]1[N:40]=[CH:41][N:42]([C:44]2[CH:53]=[CH:52][C:51]([N:54]3[CH:59]=[CH:58][CH:57]=[CH:56][C:55]3=[O:60])=[CH:50][C:45]=2[C:46]([O:48][CH3:49])=[O:47])[CH:43]=1>CN(C=O)C>[Cl:1][C:2]1[S:6][C:5]([C:7]([NH:37][CH2:38][C:39]2[N:40]=[CH:41][N:42]([C:44]3[CH:53]=[CH:52][C:51]([N:54]4[CH:59]=[CH:58][CH:57]=[CH:56][C:55]4=[O:60])=[CH:50][C:45]=3[C:46]([O:48][CH3:49])=[O:47])[CH:43]=2)=[O:9])=[CH:4][CH:3]=1
Reactant: COC(=O)c1cc(-n2ccccc2=O)ccc1-n1cnc(CN)c1
Reactant: O=C(O)c1ccc(Cl)s1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Product: COC(=O)c1cc(-n2ccccc2=O)ccc1-n1cnc(CNC(=O)c2ccc(Cl)s2)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of 5-chlorothiophene-2-carboxylic acid 1-5 (40 mg, 0.25 mmol) and TEA (0.068 mL, 0.49 mmol) in DMF (2 mL), BOP (142 mg, 0.32 mmol) was added. After 5 min of mixing, the solution was added to the sample methyl 2-(4-(aminomethyl)-1H-imidazol-1-yl)-5-(2-oxopyridin-1(2H)-yl)benzoate prepared above. The mixture was then stirred at room temperature for 1 h before it was purified by HPLC to give the title compound (4 mg). MS 469.0 and 471.0 (M+H, Cl pattern).
Reaction SMILES: [OH:1][C:2]1[CH:9]=[C:8]([OH:10])[CH:7]=[CH:6][C:3]=1[CH:4]=O.C([C:15](C(C)(C)C)([C:19]([OH:21])=[O:20])[C:16]([OH:18])=O)(C)(C)C>C(O)(C)(C)C.N1CCCCC1>[C:3]([O:21][C:19]([C:15]1[C:16](=[O:18])[O:1][C:2]2[C:3]([CH:4]=1)=[CH:6][CH:7]=[C:8]([OH:10])[CH:9]=2)=[O:20])([CH3:6])([CH3:4])[CH3:2]
Reactant: O=Cc1ccc(O)cc1O
Reactant: CC(C)(C)C(C(=O)O)(C(=O)O)C(C)(C)C
Solvent: C1CCNCC1
Solvent: CC(C)(C)O
Product: CC(C)(C)OC(=O)c1cc2ccc(O)cc2oc1=O
Yield: 53.4 %

Procedure:
2,4-dihydroxylbenzaldehyde (0.27 g, 2 mmol) and di-tert-buty malonic acid (0.43 g, 2 mmol) are dissolved in tert-butanol (5 mL), and three drops of piperidine are added. The mixture is refluxed for 16 hours to obtain a suspension. After being placed for cooling, insoluble material is removed by filtrating. The mother liquor is concentrated, and the ethyl acetate is added with stirring. The supernatant is separated, concentrated, and chromatographed over silica gel column with petroleum/ethyl acetate (3:4) as eluent to obtain 0.14 g of 7-hydroxyl-3-coumarin carboxylic acid tert-butyl ester, yield: 22.5%.
Reaction SMILES: S(Cl)([Cl:3])=O.[C:5]([C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][C:16]=1[OH:17])[NH:13][N:12]=[C:11]2[CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([CH3:25])[CH:20]=1)(O)=[O:6].C1(C)C=CC=CC=1>C1COCC1>[Cl:3][C:5]([C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][C:16]=1[OH:17])[NH:13][N:12]=[C:11]2[CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([CH3:25])[CH:20]=1)=[O:6]
Reactant: Cc1cccc(Cc2n[nH]c3cc(O)c(C(=O)O)cc23)c1
Reactant: O=S(Cl)Cl
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: Cc1cccc(Cc2n[nH]c3cc(O)c(C(=O)Cl)cc23)c1

Procedure:
4.6 0.1 ml of thionyl chloride is added to a suspension of 200 mg of “4e” in 4 ml of THF, and the mixture is stirred for a further hour. 3 ml of toluene are added, and the solvents are removed at 300, giving 5-chlorocarbonyl-6-hydroxy-3-(3-methylbenzyl)-1H-indazole (“4f”)
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:17]2[O:18][CH:19]=[C:20]([CH2:22][N:23]3C(=O)C4C(=CC=CC=4)C3=O)[N:21]=2)[CH:12]=[CH:13][C:14]=1[O:15][CH3:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.NN.ClCCl>C(O)C>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:17]2[O:18][CH:19]=[C:20]([CH2:22][NH2:23])[N:21]=2)[CH:12]=[CH:13][C:14]=1[O:15][CH3:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COc1ccc(-c2nc(CN3C(=O)c4ccccc4C3=O)co2)cc1OCc1ccccc1
Agent: NN
Solvent: O
Solvent: CCO
Solvent: ClCCl
Product: COc1ccc(-c2nc(CN)co2)cc1OCc1ccccc1

Procedure:
A 9 g quantity of the 2-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]isoindolin-1,3-dione obtained in Reference Example 6 was suspended in 200 ml of ethanol, and 3.1 ml of hydrazine monohydrate was added. The mixture was heated and refluxed for 3 hours. After cooing the reaction mixture, 200 ml of dichloromethane was added and the mixture was stirred. Insolubles were removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (NH silica, product of Fuji Sylisia Chemical Ltd., dichloromethane:methanol=20:1) to give 4.5 g of pale yellow powdery [2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-yl]methylamine.
Reaction SMILES: Cl.Cl[C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[C:6]([C:13]3[NH:22][C:16]4[N:17]=[CH:18][NH:19][C:20](=[O:21])[C:15]=4[CH:14]=3)[CH:7]=[CH:8][CH:9]=2)[N:4]=1.[NH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>>[C:24]1([NH:23][C:3]2[CH:12]=[CH:11][C:10]3[C:5](=[C:6]([C:13]4[NH:22][C:16]5[N:17]=[CH:18][NH:19][C:20](=[O:21])[C:15]=5[CH:14]=4)[CH:7]=[CH:8][CH:9]=3)[N:4]=2)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: O=c1[nH]cnc2[nH]c(-c3cccc4ccc(Cl)nc34)cc12
Reactant: Nc1ccccc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: Cl
Agent: [Li+]
Product: O=c1[nH]cnc2[nH]c(-c3cccc4ccc(Nc5ccccc5)nc34)cc12
Yield: 15.1 %

Procedure:
To 6-(2-chloroquinolin-8-yl)-3H-pyrrolo[2,3-d]pyrimidin-4(7H)-one hydrochloride (Example 19b; 0.075 g, 0.225 mmol) and aniline (0.144 ml, 1.576 mmol) was added LHMDS (1.0 M in THF; 1.576 ml, 1.576 mmol). After 1 h the reaction was partitioned between saturated aq. NH4Cl and EtOAc. The aq. layer was washed with saturated aq. NH4Cl and 1× brine, dried over Na2SO4, and concentrated in vacuo. The solid residue from the separatory funnel was rinsed with 10% DCM/MeOH into an Erlenmeyer flask, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The resulting solid was suspended in MeOH and filtered. The solid was collected to give 6-(2-(phenylamino)quinolin-8-yl)-3H-pyrrolo[2,3-d]pyrimidin-4(7H)-one (0.012 g, 0.034 mmol, 15% yield) as a dull-yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 12.43 (1H, br. s), 11.80 (1H, br. s.), 9.59 (1H, s), 8.13 (1H, d, J=9.0 Hz), 8.02 (1H, dd, J=7.4, 1.6 Hz), 7.88 (1H, s), 7.78 (2H, dd, J=8.6, 1.2 Hz), 7.67-7.73 (1H, m), 7.28-7.38 (3H, m), 7.09-7.19 (2H, m), 6.97-7.05 (1H, m). m/z (ESI, +ve) 353.9 (M+H)+.
Reaction SMILES: [C:1](O[CH2:7][CH2:8][CH2:9][CH3:10])(=O)[C:2](C)=C.[C:11](O)(=O)[CH:12]=[CH2:13].N([C:23]([CH3:27])([CH3:26])C#N)=NC(C)(C)C#N>C(OCC)(=O)C>[CH2:7]=[CH:8][C:9](=[CH2:10])[CH3:11].[CH2:13]=[CH:12][C:11]1[CH:26]=[CH:23][CH:27]=[CH:2][CH:1]=1
Reactant: CC(C)(C#N)N=NC(C)(C)C#N
Reactant: C=CC(=O)O
Reactant: C=C(C)C(=O)OCCCC
Solvent: CCOC(C)=O
Product: C=CC(=C)C
Product: C=Cc1ccccc1
Reaction time: 16 h

Procedure:
In a glass reaction bottle was placed 19.0 g butyl methacrylate, 1.0 g acrylic acid, 30 g of ethyl acetate, and 0.06 g of 2,2'-azobis(isobutyronitrile) free radical initiator available under the trade designation "VAZO" 64 from the E. I. DuPont Company. The reaction bottle was purged with nitrogen and sealed. It was placed in a 55° C. bath and tumbled therein for 60 hours to produce a polymer which had an inherent viscosity of 0.58 dl/g. The resulting polymer solution was diluted with 50 g ethyl acetate and knife coated onto a 37 micrometer polyester film to provide a dry coating thickness of 10 micrometers. The coated film was equilibrated for 16 hours and thereafter tested under constant temperature and humidity. Test results for adhesion of an acrylic PSA (Tape A) and a tackified styrene isoprene block copolymer PSA (Tape B) are shown in Table IV.
Reaction SMILES: C([NH:5][S:6]([C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:16]=[C:17]([NH:21][C:22](=[O:47])[N:23]([CH2:32][CH2:33][CH:34]([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[CH2:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=3)[S:18][C:19]=2[Cl:20])=[CH:11][CH:10]=1)(=[O:8])=[O:7])(C)(C)C.C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:20][C:19]1[S:18][C:17]([NH:21][C:22](=[O:47])[N:23]([CH2:32][CH2:33][CH:34]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH2:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=2)=[N:16][C:15]=1[C:12]1[CH:13]=[CH:14][C:9]([S:6]([NH2:5])(=[O:7])=[O:8])=[CH:10][CH:11]=1
Reactant: CC(C)(C)NS(=O)(=O)c1ccc(-c2nc(NC(=O)N(CCc3ccccn3)CCC(c3ccccc3)c3ccccc3)sc2Cl)cc1
Solvent: O=C(O)C(F)(F)F
Solvent: COc1ccccc1
Solvent: ClCCl
Product: NS(=O)(=O)c1ccc(-c2nc(NC(=O)N(CCc3ccccn3)CCC(c3ccccc3)c3ccccc3)sc2Cl)cc1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
To a solution of N-tert-butyl-4-(5-chloro-2-(((3,3-diphenylpropyl)(2-(2-pyridinyl)ethyl)carbamoyl)amino)-1,3-thiazol-4-yl)benzenesulfonamide 84 (0.187 g, 0.272 mmol) in DCM (1 mL) was added anisol (0.20 mL) and TFA (2 mL). The reaction mixture was stirred at room temperature for 1 d and concentrated. The concentrate was diluted with EtOAc and the organic phase was washed with saturated NaHCO3 (1×), brine (1×), dried over MgSO4, filtered, and concentrated. Purification by crystallization from a mixture of DCM and hexanes gave 4-(5-chloro-2-(((3,3-diphenylpropyl)(2-(2-pyridinyl)ethyl)carbamoyl)amino)-1,3-thiazol-4-yl)benzenesulfonamide 85. Mass spectrum, calculated for C32H30ClN5O3S2 631.2; found 632.1 (M++1).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH2:5][NH2:6].C([O:14][C:15]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[C:23]1[CH:28]=[CH:27][C:26]([CH2:29][N:30]2[C:38]3[C:33](=[CH:34][C:35]([C:39]([OH:41])=O)=[CH:36][CH:37]=3)[C:32]([CH3:42])=[C:31]2[CH3:43])=[CH:25][CH:24]=1)=[O:16])(C)(C)C>>[CH3:43][C:31]1[N:30]([CH2:29][C:26]2[CH:27]=[CH:28][C:23]([C:18]3[C:17]([C:15]([OH:14])=[O:16])=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:24][CH:25]=2)[C:38]2[C:33]([C:32]=1[CH3:42])=[CH:34][C:35]([C:39](=[O:41])[NH:6][CH2:5][C:4]1[CH:7]=[CH:8][CH:9]=[C:2]([CH3:1])[CH:3]=1)=[CH:36][CH:37]=2
Reactant: Cc1cccc(CN)c1
Reactant: Cc1c(C)n(Cc2ccc(-c3ccccc3C(=O)OC(C)(C)C)cc2)c2ccc(C(=O)O)cc12
Product: Cc1cccc(CNC(=O)c2ccc3c(c2)c(C)c(C)n3Cc2ccc(-c3ccccc3C(=O)O)cc2)c1

Procedure:
The title compound was prepared following the same general protocol as described in Steps 8-9, Example 1, using 3-methylbenzylamine and 1-((2′-(tert-butoxycarbonyl)biphenyl-4-yl)methyl)-2,3-dimethyl-1H-indole-5-carboxylic acid.
Reaction SMILES: [NH2:1][C@H:2]([C:10]([OH:12])=[O:11])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C(N(CC)CC)C.O1CCOCC1.[C:26](=[S:28])=O.Cl[CH2:30][C:31]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH:34]=[CH:33][CH:32]=1>O>[C:31]1([CH2:30][C:26]([NH:1][C@H:2]([C:10]([OH:12])=[O:11])[CH2:3][C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)=[S:28])[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH:34]=[CH:33][CH:32]=1
Reactant: ClCc1cccc2ccccc12
Reactant: O=C=S
Reactant: N[C@@H](Cc1ccccc1)C(=O)O
Solvent: O
Solvent: CCN(CC)CC
Solvent: C1COCCO1
Product: O=C(O)[C@H](Cc1ccccc1)NC(=S)Cc1cccc2ccccc12
Temperature: 10 °C
Reaction time: 0.25 h
Yield: 81.1 %

Procedure:
8.3 G (0.05 mol) of L-phenylalanine and 13.9 ml (0.1 mol) of triethylamine were dissolved in 100 ml of water. To the solution was dropwise added 100 ml of dioxane containing 3.0 g (0.05 mol) of carbonyl sulfide at a temperature of from 5°to 10° C. in 15 minutes while cooling with ice. After stirring at a temperature of 10° C. for 15 minutes, 8.8 g (0.05 mol) of 1-(chloromethyl)-naphthalene was dropwise added to the mixture in 10 minutes and the mixture was then stirred at room temperature for 1 hour. After completion of reaction, the syrup-like substance obtained in a similar manner to that described in Example 6 was crystallized from 80 ml of ether and 100 ml of n-hexane to yield 14.8 g of white crystals.
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([C:8]2[CH:17]=[CH:16][CH:15]=[CH:14][C:9]=2[C:10]([O:12][CH3:13])=[O:11])[CH:3]=1.C(N(CC)CC)C>CO.[C].[Pd]>[N:7]1[CH:2]=[CH:3][C:4]([C:8]2[CH:17]=[CH:16][CH:15]=[CH:14][C:9]=2[C:10]([O:12][CH3:13])=[O:11])=[N:5][CH:6]=1
Reactant: COC(=O)c1ccccc1-c1cc(Cl)ncn1
Agent: [Pd]
Solvent: CO
Solvent: CCN(CC)CC
Product: COC(=O)c1ccccc1-c1ccncn1
Temperature: 25 °C
Reaction time: 1 h
Yield: 94.8 %

Procedure:
A suspension of methyl 2-(6-chloropyrimidin-4-yl)benzoate (0.60 g), triethylamine (1.7 mL) and 10% palladium carbon (containing water (50%), 0.26 g) in methanol (20 mL) was stirred at room temperature for 1 hr under a hydrogen atmosphere. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. To the residue was added ethyl acetate, and the mixture was washed with saturated brine. The extract was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to give the title compound (0.49 g).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)/[C:7](=[CH:11]\[C:12]1[CH:17]=[CH:16][C:15]([S:18][CH3:19])=[CH:14][CH:13]=1)/[C:6]([CH3:20])=[C:5]2[CH2:21][CH2:22][O:23][NH2:24].[CH:25]([CH:27]=O)=[O:26]>>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)/[C:7](=[CH:11]\[C:12]1[CH:17]=[CH:16][C:15]([S:18][CH3:19])=[CH:14][CH:13]=1)/[C:6]([CH3:20])=[C:5]2[CH2:21][CH2:22][O:23][N:24]=[CH:27][CH:25]=[O:26]
Reactant: CSc1ccc(/C=C2/C(C)=C(CCON)c3cc(F)ccc32)cc1
Reactant: O=CC=O
Product: CSc1ccc(/C=C2/C(C)=C(CCON=CC=O)c3cc(F)ccc32)cc1

Procedure:
The title compound is prepared by reaction of O-2-[Z-5-fluoro-2-methyl-1-(4-methylthiophenyl)methylene-1H-inden-3-yl]ethyl hydroxylamine with glyoxal by the method of Example 1.
Reaction SMILES: [C:1](Cl)(=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].[Cl:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[C:26]1([CH:29]2[C:38]3[C:33](=[CH:34][C:35]([O:40][CH3:41])=[C:36]([OH:39])[CH:37]=3)[CH2:32][CH2:31][N:30]2[CH3:42])[CH2:28][CH2:27]1.C(N(CC)CC)C>ClCCl>[Cl:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[C:26]1([CH:29]2[C:38]3[C:33](=[CH:34][C:35]([O:40][CH3:41])=[C:36]([O:39][C:1](=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[CH:37]=3)[CH2:32][CH2:31][N:30]2[CH3:42])[CH2:28][CH2:27]1
Reactant: COc1cc2c(cc1O)C(C1(c3ccccc3Cl)CC1)N(C)CC2
Reactant: CCCCCCCCCCCCCCCC(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCCCCCCCCCCCCCC(=O)Oc1cc2c(cc1OC)CCN(C)C2C1(c2ccccc2Cl)CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Hexadecanoyl chloride (0.83 g) in dichloromethane (5 ml) was added dropwise to a stirring solution of 1-[1-(2-chlorophenyl)cyclopropyl]-7-hydroxy-6-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline (1.04 g, prepared from the (+)-enantiomer of the hydrobromide salt, prepared in a similar manner to that described in Example 77), triethylamine (0.91 g) and dichloromethane (20 ml). The mixture was stirred at ambient temperature for 2 hours, then washed with dilute sodium hydroxide solution, water and brine. The organic phase was dried over magnesium sulphate, filtered and concentrated in vacuo. The resulting oil was dissolved in petroleum ether (b.p. 60°-80° C.) and washed repeatedly with water. The organic layer was dried over magnesium sulphate, filtered and concentrated in vacuo to yield (+)-1-[1-(2-chlorophenyl)cyclopropyl]-7-hexadecanoyloxy-6-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinoline (1.45 g) which had a specific optical rotation αD of +21.18°.
Reaction SMILES: [C@@H:1]12[N:8](C)[C@@H:5]([CH2:6][CH2:7]1)[CH2:4][CH2:3][CH2:2]2.[Cl:10]C(OC(Cl)C)=O.C1(C)C=CC=CC=1>CO>[ClH:10].[CH:5]12[NH:8][CH:1]([CH2:7][CH2:6]1)[CH2:2][CH2:3][CH2:4]2
Reactant: CC(Cl)OC(=O)Cl
Reactant: CN1[C@@H]2CCC[C@H]1CC2
Solvent: Cc1ccccc1
Solvent: CO
Product: C1CC2CCC(C1)N2
Product: Cl

Procedure:
A mixture of tropane (900 mg), 1-chloroethyl chloroformate (1 ml), and toluene (20 ml) was heated and refluxed for 6 hours. After that, methanol (10 ml) was added to the reaction solution, and further refluxed for 4 hours. The solvent was distilled to yield the title compound (850 mg).
Reaction SMILES: S(Cl)([Cl:3])=O.[CH3:5][C:6]1[C:7](=[CH:11][C:12](=[S:23](=[O:25])=[O:24])[CH:13]([CH3:22])[C:14]=1[C:15]1[CH2:19][CH:18]([CH2:20][Cl:21])[O:17][N:16]=1)[C:8](O)=[O:9]>CN(C)C=O.C1(C)C=CC=CC=1>[CH3:5][C:6]1[C:7](=[CH:11][C:12](=[S:23](=[O:25])=[O:24])[CH:13]([CH3:22])[C:14]=1[C:15]1[CH2:19][CH:18]([CH2:20][Cl:21])[O:17][N:16]=1)[C:8]([Cl:3])=[O:9]
Reactant: O=S(Cl)Cl
Reactant: CC1=C(C2=NOC(CCl)C2)C(C)C(=S(=O)=O)C=C1C(=O)O
Solvent: Cc1ccccc1
Solvent: CN(C)C=O
Product: CC1=C(C2=NOC(CCl)C2)C(C)C(=S(=O)=O)C=C1C(=O)Cl

Procedure:
3.23 g (27.2 mmol) of thionyl chloride were added dropwise to a mixture of 4.5 g (13.6 mmol) of 2-methyl-3-(5-chloromethyl-4,5-dihydroisoxazol-3-yl)-4-methyl-sulfonylbenzoic acid, 100 ml of toluene and three drops of N,N-dimethylformamide. The mixture was refluxed for 4 hours and then cooled, and the solvent was removed. The residue was then taken up in methylene chloride and once more concentrated to dryness. This gave 4.74 g (100% of theory) of the title compound in the form of a pale powder.
Reaction SMILES: [C:1]1([B-:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[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.[Na+].O.Cl.[C:29]([P:33]([C:38]([CH3:41])([CH3:40])[CH3:39])[C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:32])([CH3:31])[CH3:30]>C1(C)C=CC=CC=1>[C:20]1([B-:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1.[C:38]([PH+:33]([C:29]([CH3:32])([CH3:31])[CH3:30])[C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:39])([CH3:40])[CH3:41]
Reactant: CC(C)(C)P(C(C)(C)C)C(C)(C)C
Agent: Cl
Agent: [Na+]
Agent: c1ccc([B-](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: CC(C)(C)[PH+](C(C)(C)C)C(C)(C)C
Temperature: 25 °C

Procedure:
A 300-ml four-necked flask was equipped with a stirrer, a thermometer and a reflux condenser. 15.1 g (44 mmol) of sodium tetraphenylborate and 60 ml of water were weighed in the flask, followed by stirring to dissolve sodium tetraphenylborate. While the stirring was continuously carried out, the aqueous solution of tri-tert-butylphosphine hydrochloride was added to the solution, and the mixture was stirred at 25° C. for 3 hours. After the completion of the reaction, the precipitated product was filtered off. The so obtained crystal was suspended in 100 ml of toluene at 50° C., and the suspension was cooled to 25° C. and filtered. The product filtered off was washed with 100 ml of toluene. The crystal was then suspended in 100 ml of methanol at 50° C., and the suspension was cooled to 25° C. and filtered. The product filtered off was washed with 100 ml of methanol. The crystal obtained was dried to give 18.2 g of objective tri-tert-butylphosphonium tetraphenylborate as white crystal. The yield (mol %) was 87% based on tri-tert-butylphosphine.