Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[NH:8][N:7]=[C:6]([CH2:9][C:10]([OH:12])=O)[N:5]=1)([O-:3])=[O:2].[CH2:13]([C@@H:20]1[NH:25][CH2:24][CH2:23][N:22]([C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[C:28]([O:34][CH:35]([CH3:37])[CH3:36])[CH:27]=2)[CH2:21]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>>[CH2:13]([C@H:20]1[CH2:21][N:22]([C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[C:28]([O:34][CH:35]([CH3:37])[CH3:36])[CH:27]=2)[CH2:23][CH2:24][N:25]1[C:10](=[O:12])[CH2:9][C:6]1[N:5]=[C:4]([N+:1]([O-:3])=[O:2])[NH:8][N:7]=1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: O=C(O)Cc1n[nH]c([N+](=O)[O-])n1
Reactant: COc1ccc(N2CCN[C@@H](Cc3ccccc3)C2)cc1OC(C)C
Product: COc1ccc(N2CCN(C(=O)Cc3n[nH]c([N+](=O)[O-])n3)[C@@H](Cc3ccccc3)C2)cc1OC(C)C

Procedure:
Prepared by the method outlined for Example 189 using (5-Nitro-1H-[1,2,4]triazol-3-yl)-acetic acid and 3 (S)-benzyl-1-(3-(1-methylethoxy)-4-methoxy-phenyl)-piperazine (Example 9, Compound 97) as starting materials. Product as an oil. LC/MS (Method B) 3.10 min, [M+1]+ 495. Potency class C.
Reaction SMILES: [C:1]([CH:5]([NH:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][N:20]2[C:24]3=[N:25][C:26]([CH3:30])=[CH:27][C:28]([CH3:29])=[C:23]3[N:22]=[C:21]2[CH2:31][CH3:32])=[CH:15][CH:14]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)([O:3][CH3:4])=[O:2].[CH2:33](Br)[CH:34]([CH3:36])[CH3:35]>>[C:1]([CH:5]([N:12]([C:13]1[CH:18]=[CH:17][C:16]([CH2:19][N:20]2[C:24]3=[N:25][C:26]([CH3:30])=[CH:27][C:28]([CH3:29])=[C:23]3[N:22]=[C:21]2[CH2:31][CH3:32])=[CH:15][CH:14]=1)[CH2:33][CH:34]([CH3:36])[CH3:35])[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1)([O:3][CH3:4])=[O:2]
Reactant: CC(C)CBr
Reactant: CCc1nc2c(C)cc(C)nc2n1Cc1ccc(NC(C(=O)OC)c2ccccc2)cc1
Product: CCc1nc2c(C)cc(C)nc2n1Cc1ccc(N(CC(C)C)C(C(=O)OC)c2ccccc2)cc1

Procedure:
Using the general procedure for the alkylation of secondary amines described in Step A of Example 29, 3-[4-(N-(1-carbomethoxy-1-phenylmethylamino)phenylmethyl]-5,7-dimethyl-2-ethyl-3H-imidazo[4,5-b]pyridine (Step A, Example 28) was alkylated with iso-butyl bromide. Standard workup and purification by flash chromatography afforded the title compound.
Reaction SMILES: [F:1][C:2]1[C:3]2[C:8]([C:9]3[CH:10]=[CH:11][C:12](Br)=[CH:13][C:14]=3[C:15]=1[F:16])=[CH:7][CH:6]=[C:5]([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[CH:4]=2.[CH2:26]([Mg]Br)[CH2:27][CH2:28][CH2:29][CH2:30][CH3:31]>>[F:1][C:2]1[C:3]2[C:8]([C:9]3[CH:10]=[CH:11][C:12]([CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])=[CH:13][C:14]=3[C:15]=1[F:16])=[CH:7][CH:6]=[C:5]([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[CH:4]=2
Reactant: CCCCCC[Mg]Br
Reactant: CCCCCCCCc1ccc2c(c1)c(F)c(F)c1cc(Br)ccc12
Product: CCCCCCCCc1ccc2c(c1)c(F)c(F)c1cc(CCCCCC)ccc12

Procedure:
In analogy to Example 2, from 9,10-difluoro-2-bromo-7-octylphenanthrene and 10 mmol of hexylmagnesium bromide. The catalyst used is 0.2 mmol of 1,3-bis(diphenylphosphine)propanenickel(lI) chloride. Chromatography gives 9,10-difluoro-2-hexyl-7-octylphenanthrene.
Reaction SMILES: [N+](C1C=CC(O[C:11](=[O:36])[NH:12][CH:13]2[CH2:25][C:24]3[C:23]4[C:18](=[CH:19][CH:20]=[C:21]([C:26]#[N:27])[CH:22]=4)[N:17]([CH2:28][C:29]4[CH:34]=[CH:33][CH:32]=[C:31]([F:35])[CH:30]=4)[C:16]=3[CH2:15][CH2:14]2)=CC=1)([O-])=O.Cl.CN.[CH2:40]([N:42](CC)CC)C.C1COCC1>O>[C:26]([C:21]1[CH:22]=[C:23]2[C:18](=[CH:19][CH:20]=1)[N:17]([CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([F:35])[CH:30]=1)[C:16]1[CH2:15][CH2:14][CH:13]([NH:12][C:11]([NH:42][CH3:40])=[O:36])[CH2:25][C:24]2=1)#[N:27]
Reactant: CCN(CC)CC
Reactant: N#Cc1ccc2c(c1)c1c(n2Cc2cccc(F)c2)CCC(NC(=O)Oc2ccc([N+](=O)[O-])cc2)C1
Agent: CN
Agent: Cl
Solvent: C1CCOC1
Solvent: O
Product: CNC(=O)NC1CCc2c(c3cc(C#N)ccc3n2Cc2cccc(F)c2)C1
Temperature: 25 °C
Reaction time: 18 h
Yield: 24.5 %

Procedure:
Combine [6-cyano-9-(3-fluorobenzyl)-2,3,4,9-tetrahydro-1H-carbazol-3-yl]-carbamic acid 4-nitrophenyl ester (Preparation 55) (306 mg, 0.63 mmol), methylamine hydrochloride (426 mg, 6.30 mmol), triethylamine (1.40 g, 1.93 mL, 13.9 mmol), and THF (30 mL). Stir the reaction mixture at room temperature for 18 h, then dilute with water (100 mL). Extract into EtOAc (3×65 mL), dry the combined organic portions (MgSO4), filter, and concentrate to give the crude product (310 mg) as a yellow oil. Purify the crude product on 40 g silica gel (50-100% (4% (2M NH3/MeOH)/CH2Cl2)/hexanes) to give 58 mg (24%) of the title compound as a yellow solid. MS (ES): m/z 377 (M+1); HPLC (Method B): Rt=3.22 min (98%).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([C:11]([OH:13])=O)[CH:10]=2)[CH:7]=1.[CH3:14][C:15]1[O:23][C:22]2[CH2:21][CH2:20][NH:19][CH:18]([CH3:24])[C:17]=2[CH:16]=1>>[Br:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([C:11]([N:19]3[CH2:20][CH2:21][C:22]4[O:23][C:15]([CH3:14])=[CH:16][C:17]=4[CH:18]3[CH3:24])=[O:13])[CH:10]=2)[CH:7]=1
Reactant: O=C(O)c1cc2ncc(Br)cn2n1
Reactant: Cc1cc2c(o1)CCNC2C
Product: Cc1cc2c(o1)CCN(C(=O)c1cc3ncc(Br)cn3n1)C2C
Yield: 12 %

Procedure:
In close analogy to the procedure described in Example 1, 6-bromo-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid is reacted with 2,4-Dimethyl-4,5,6,7-tetrahydro-furo[3,2-c]pyridine to provide the title compound.
Reaction SMILES: [ClH:1].FC1C=CC2OC=C(CCCN3CCN(C4C(OC)=CC=CN=4)CC3)C=2C=1.[S:29]([O:39][CH2:40][CH2:41][CH2:42][C:43]1[C:44]2[CH:51]=[C:50]([O:52][CH3:53])[CH:49]=[CH:48][C:45]=2[O:46][CH:47]=1)([C:32]1[CH:38]=[CH:37][C:35]([CH3:36])=[CH:34][CH:33]=1)(=[O:31])=[O:30].[CH3:54][O:55][C:56]1[C:57]([N:62]2[CH2:67][CH2:66][NH:65][CH2:64][CH2:63]2)=[N:58][CH:59]=[N:60][CH:61]=1.BrC1C=C(OC)C=CC=1O.S(OCCCC1C2C=C(F)C=CC=2OC=1)(C1C=CC(C)=CC=1)(=O)=O>>[ClH:1].[CH3:53][O:52][C:50]1[CH:49]=[CH:48][C:45]2[O:46][CH:47]=[C:43]([CH2:42][CH2:41][CH2:40][N:65]3[CH2:66][CH2:67][N:62]([C:57]4[C:56]([O:55][CH3:54])=[CH:61][N:60]=[CH:59][N:58]=4)[CH2:63][CH2:64]3)[C:44]=2[CH:51]=1.[S:29]([O:39][CH2:40][CH2:41][CH2:42][C:43]1[C:44]2[CH:51]=[C:50]([O:52][CH3:53])[CH:49]=[CH:48][C:45]=2[O:46][CH:47]=1)([C:32]1[CH:33]=[CH:34][C:35]([CH3:36])=[CH:37][CH:38]=1)(=[O:30])=[O:31]
Reactant: COc1cncnc1N1CCNCC1
Agent: COc1ccc(O)c(Br)c1
Agent: COc1ccc2occ(CCCOS(=O)(=O)c3ccc(C)cc3)c2c1
Agent: COc1cccnc1N1CCN(CCCc2coc3ccc(F)cc23)CC1
Product: COc1ccc2occ(CCCN3CCN(c4ncncc4OC)CC3)c2c1

Procedure:
The title compound was prepared (0.31 g, 87%, mp 196°-198° C.) in a manner analogous to the preparation of 1-[3-(5-fluorobenzo[b]furan-3-yl)propyl]-4-(3-methoxy-2-pyridinyl)piperazine hydrochloride (Example 20) by the reaction of 5-methoxy-3-benzo[b]furanpropanol tosylate with 1-(5-methoxy-4-pyrimidinyl)piperazine. 5-Methoxy-3-benzo[b]furanpropanol tosylate was prepared from 2-bromo-4-methoxyphenol in a manner analogous to the preparation of 5-fluoro-3-benzo[b]furanpropanol tosylate (Example 21).
Reaction SMILES: [N+:1]([O-:4])(O)=[O:2].OS(O)(=O)=O.[F:10][C:11]1[CH:12]=[C:13]([CH:17]=[C:18]([F:20])[CH:19]=1)[C:14]([OH:16])=[O:15]>>[F:10][C:11]1[C:12]([N+:1]([O-:4])=[O:2])=[C:13]([CH:17]=[C:18]([F:20])[CH:19]=1)[C:14]([OH:16])=[O:15]
Reactant: O=C(O)c1cc(F)cc(F)c1
Reactant: O=[N+]([O-])O
Agent: O=S(=O)(O)O
Product: O=C(O)c1cc(F)cc(F)c1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 8 h
Yield: 80 %

Procedure:
10.0 mL of conc. HNO3 at 0° C. was treated with 20.0 mL of conc. H2SO4, then 6.4 g (40 mmol) of 3,5-difluorobenzoic acid. The reaction mixture was warmed to room temperature and stirred overnight, then poured into a beaker containing ice. The resulting solid was collected, washed with cold water and dried to produce 8.0 g (80%) of 3,5-difluoro-2-nitro-benzoic acid. LCMS: 204 (M+1)+.
Reaction SMILES: C([O:4][CH:5]1[O:22][C@H:21]([CH2:23][Cl:24])[C@H:16]([O:17][C:18](=[O:20])[CH3:19])[C@H:11]([O:12][C:13](=[O:15])[CH3:14])[C@H:6]1[O:7][C:8](=[O:10])[CH3:9])(=O)C.C(O)(=O)C.NN.ClCCl>CN(C=O)C>[C:8]([O:7][C@@H:6]1[C@@H:11]([O:12][C:13](=[O:15])[CH3:14])[C@@H:16]([O:17][C:18](=[O:20])[CH3:19])[C@@H:21]([CH2:23][Cl:24])[O:22][C@@H:5]1[OH:4])(=[O:10])[CH3:9]
Reactant: CC(=O)OC1O[C@H](CCl)[C@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O
Agent: NN
Solvent: CC(=O)O
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@@H](O)O[C@H](CCl)[C@@H]1OC(C)=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 103.1 %

Procedure:
To a solution of tetra-O-acetyl-6-chloro-6-deoxy-D-galactopyranose (compound 54) (6.36 g, 17.3 mmol) in DMF (60 mL) was added hydrazine acetate (2.4 g, 26.0 mmol). The mixture was stirred for 1 hour at room temperature and then 1 L of dichloromethane was added and the resulting solution washed 4 times with water. The organic layer was dried over anhydrous sodium sulfate and evaporated. Flash column chromatography using hexane-ethyl acetate (1:1) as the eluent gave 2,3,4-tri-O-acetyl-6-chloro-6-deoxy-α-D-galactopyranose (5.79 g). This material was dissolved in 50 mL of dichloromethane and cooled to 0° C. Trichloroacetonitrile (8.93 mL, 89.2 mmol) was added followed by DBU (1.33 mL, 8.9 mmol). This solution was stirred for 1.5 hours and then evaporated. The residue was chromatographed on a silica gel column, eluting with hexane-ethyl acetate (2:1), to provide compound 55 (4.1 g, 51%) as a foam.
Reaction SMILES: C([O:8][C:9]1[CH:17]=[CH:16][C:15]2[NH:14][C:13]3[C:18](=[CH:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:19][CH2:20][C:12]=3[C:11]=2[CH:10]=1)C1C=CC=CC=1.C(OCC)(=O)C.C(O)=O>[Pd].C(N(CC)CC)C>[OH:8][C:9]1[CH:17]=[CH:16][C:15]2[NH:14][C:13]3[CH:18]([CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:19][CH2:20][C:12]=3[C:11]=2[CH:10]=1
Reactant: CCOC(=O)C=C1CCc2c1[nH]c1ccc(OCc3ccccc3)cc21
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: O=CO
Solvent: CCN(CC)CC
Product: CCOC(=O)CC1CCc2c1[nH]c1ccc(O)cc21
Temperature: 35 °C
Reaction time: 0.03 h
Yield: 49.7 %

Procedure:
The E/Z mixture of ethyl 2-(7-(benzyloxy)-1,2-dihydrocyclopenta[b]indol-3(4H)-ylidene)acetate (7.5 g, 21.59 mmol) and 10% Pd/C (50% wet; 1.13 g, 10.58 mmol) were taken up in ethyl acetate (60 mL, 613 mmol). The suspension was degassed 3× with N2 and followed with pre-activation of the catalyst with the addition of formic acid (2.48 mL, 64.8 mmol). The mixture was allowed to stir for 1-2 min. Triethylamine (9.03 mL, 64.8 mmol) was charged portion-wise maintaining the temperature<35° C. Upon complete addition of triethylamine, the mixture was stirred for about 5-10 minutes followed with heating to 50° C. The reaction progression was followed by HPLC to monitor the complete consumption of starting material (i.e., E/Z mixture of ethyl 2-(7-(benzyloxy)-1,2-dihydrocyclopenta[b]indol-3(4H)-ylidene)acetate) and the debenzylated intermediate. Approximately after 4 h at 50° C., the solution was cooled to about 20° C., the Pd/C was removed via vacuum filtration and rinsed with ethyl acetate (30 mL). To the filtrate was added water (75 mL) and the biphasic mixture was partitioned. The organics were washed with water (2×60 mL), concentrated under vacuum with a bath temp of 40° C. to a minimum stir volume, chased with ethyl acetate (1×37.5 mL) and further concentrated under vacuum to a minimum stir volume. Ethyl acetate (11 mL) was charged to the crude mixture and the resulting solution was heated to 60° C. Heptanes (34 mL) were charged maintaining the internal temperature at 60° C. The solution was slowly cooled to 10° C. and held for 30 min. The slurry was filtered, the filter cake rinsed with heptanes (2×52.5 mL) and the solids dried in the vacuum oven set to 40° C. to afford the title compound (2.78 g, 74.5% yield) as light beige solids.
Reaction SMILES: C1(S[CH2:8][N:9]2[C:13](=[O:14])[CH:12]([CH2:15][CH2:16][CH3:17])[N:11]([CH3:18])[S:10]2(=[O:20])=[O:19])C=CC=CC=1.S(Cl)([Cl:24])(=O)=O>C(Cl)Cl>[Cl:24][CH2:8][N:9]1[C:13](=[O:14])[CH:12]([CH2:15][CH2:16][CH3:17])[N:11]([CH3:18])[S:10]1(=[O:20])=[O:19]
Reactant: O=S(=O)(Cl)Cl
Reactant: CCCC1C(=O)N(CSc2ccccc2)S(=O)(=O)N1C
Solvent: ClCCl
Product: CCCC1C(=O)N(CCl)S(=O)(=O)N1C
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of 2-phenylthiomethyl-4-propyl-5-methyl-1,2,5-thiadiazolidin-3-one 1,1-dioxide (8.4 g) in 150 ml of methylene chloride was added sulfuryl chloride (3.22 ml) and the mixture was stirred for 3 hours at room temperature. The mixture was concentrated in vacuo and the residue was purified by flash chromatography (silica gel) to afford 5.7 g of 2-chloromethyl-4-propyl-5-methyl-1,2,5-thiadiazolidin-3-one 1,1-dioxide (Formula II: R1 =H; R2 =propyl; R3 =CH3 ; X=Cl) as a solid.
Reaction SMILES: C([O:3][CH2:4][CH2:5][CH2:6][N:7]1[C:12](=[O:13])[C:11]2[C:14]([CH2:29][C:30]3[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=3)=[C:15]([O:18][C:19]3[CH:20]=[N:21][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:23][CH:24]=3)[CH:16]=[N:17][C:10]=2[N:9]([CH3:37])[C:8]1=[O:38])=O.O[Li].O>C1COCC1.O.CC(=O)OCC>[Cl:36][C:33]1[CH:32]=[CH:31][C:30]([CH2:29][C:14]2[C:11]3[C:12](=[O:13])[N:7]([CH2:6][CH2:5][CH2:4][OH:3])[C:8](=[O:38])[N:9]([CH3:37])[C:10]=3[N:17]=[CH:16][C:15]=2[O:18][C:19]2[CH:20]=[N:21][C:22]([C:25]([F:27])([F:26])[F:28])=[CH:23][CH:24]=2)=[CH:35][CH:34]=1
Reactant: Cn1c(=O)n(CCCOC=O)c(=O)c2c(Cc3ccc(Cl)cc3)c(Oc3ccc(C(F)(F)F)nc3)cnc21
Agent: [Li]O
Solvent: O
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: Cn1c(=O)n(CCCO)c(=O)c2c(Cc3ccc(Cl)cc3)c(Oc3ccc(C(F)(F)F)nc3)cnc21
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 34.7 %

Procedure:
To a solution of 3-(5-(4-chlorobenzyl)-1-methyl-2,4-dioxo-6-(6-(trifluoromethyl)pyridin-3-yloxy)-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate (20 mg, 0.036 mmol) in THF (2 mL) and water (2 mL) was added LiOH.H2O (4.6 mg, 0.109 mmol). The reaction was stirred at RT for 30 min then diluted with EA (10 mL) and water (10 mL). The organic layer was dried over Na2SO4 filtered and concentrated to a residue which was purified by Prep HPLC to give 5-(4-chlorobenzyl)-3-(3-hydroxypropyl)-1-methyl-6-(6-(trifluoromethyl)pyridin-3-yloxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (6.5 mg, 34.2% yield) as a white solid. 1H NMR (CDCl3) δ: 8.44 (d, J=3.2 Hz, 1H), 8.21 (s, 1H), 7.84 (d, J=3.2 Hz, 1H), 7.57 (s, 1H), 7.28-7.24 (overlap with CDCl3, 2H), 7.12 (t, J=8.8 Hz, 2H), 4.25 (t, J=6.0 Hz, 2H), 4.08 (s, 2H), 3.74 (s, 3H), 3.61-3.54 (m, 2H), 2.93 (brd s, 1H), 1.97-1.90 (m, 2H). LCMS: MH+ 521 and TR=2.625 min.
Reaction SMILES: [CH2:1]([OH:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[C:12](O)(=[O:24])/[CH:13]=[CH:14]/[C:15]1[CH:23]=[CH:22][C:20]([OH:21])=[C:17]([O:18][CH3:19])[CH:16]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[C:12]([O:11][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10])(=[O:24])/[CH:13]=[CH:14]/[C:15]1[CH:23]=[CH:22][C:20]([OH:21])=[C:17]([O:18][CH3:19])[CH:16]=1
Reactant: COc1cc(/C=C/C(=O)O)ccc1O
Reactant: CCCCCCCCCCO
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CCCCCCCCCCOC(=O)/C=C/c1ccc(O)c(OC)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 76.2 %

Procedure:
n-Decanol (1.58 g, 10.0 mmol), ferulic acid (1.94 g, 10.0 mmol) and triphenylphosphine (2.88 g, 11.0 mmol) were dissolved in THF (20 ml), and DIAD (40% solution of diisopropyl azodicarboxylate in toluene, 5.56 g, 11.0 mmol) was added to the solution. The reaction mixture was stirred at room temperature for 16 hr and concentrated under reduced pressure. Ethyl acetate (100 ml) was added to the residue, and the mixture was washed with 5% aqueous citric acid solution (25 ml×3) and saturated brine (25 ml) and dried over anhydrous magnesium sulfate. Magnesium sulfate was filtered off, and the filtrate was concentrated under reduced pressure. The residue was developed by PTLC (n-hexane:ethyl acetate=2:1), and silica gel containing the object product was stirred with ethyl acetate (100 ml) for 30 min for extraction. The silica gel was filtered off, and the filtrate was concentrated under reduced pressure to give n-decanyl ferulate (2.55 g, yield 76.2%) as a colorless oil.
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[O:3][C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([NH2:10])[C:5]=1[NH2:11].CO[C:16]1C(OC)=C[C:19]2[NH:20][C:21](CCCNC)=N[C:18]=2[CH:17]=1>>[CH3:21][NH:20][CH2:19][CH2:18][CH2:17][C:16]1[NH:10][C:6]2[CH:7]=[CH:8][CH:9]=[C:4]([O:3][C:2]([F:12])([F:13])[F:1])[C:5]=2[N:11]=1
Reactant: Nc1cccc(OC(F)(F)F)c1N
Reactant: CNCCCc1nc2cc(OC)c(OC)cc2[nH]1
Product: CNCCCc1nc2c(OC(F)(F)F)cccc2[nH]1

Procedure:
Prepared from 3-trifluoromethoxy-benzene-1,2-diamine in analogy to the methods described for [3-(5,6-dimethoxy-1H-benzoimidazol-2-yl)-propyl]-methyl-amine.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:16]=[CH:15][C:9]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:8][C:7]=1[O:17][CH3:18].[N+:19]([O-])([OH:21])=[O:20]>ClCCl.C(O)(=O)C>[Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:16]=[CH:15][C:9]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[C:8]([N+:19]([O-:21])=[O:20])[C:7]=1[O:17][CH3:18]
Reactant: O=[N+]([O-])O
Reactant: CCOC(=O)c1ccc(OCCCCl)c(OC)c1
Solvent: ClCCl
Solvent: CC(=O)O
Product: CCOC(=O)c1ccc(OCCCCl)c(OC)c1[N+](=O)[O-]
Yield: 82 %

Procedure:
WO 02/36587 describes a process for preparing a 5-alkoxy-4-halogenoalkoxy-2-nitrobenzoic acid compound from a 3-alkoxy-4-hydroxybenzoic acid compound. For example, ethyl vanillate (i.e., ethyl 4-hydroxy-3-methoxybenzoate) is reacted with 3-bromo-1-chloropropane in an aqueous potassium carbonate solution in the presence of N-butyl-ammonium bromide to produce ethyl 4-(3-chloropropoxy)-3-methoxybenzoate, and the ethyl 4-(3-chloropropoxy)-3-methoxybenzoate is reacted with 70% nitric acid in a mixture of dichloromethane and acetic acid, to give ethyl 4-chloropropoxy-3-methoxy-2-nitrobenzoate in 82% yield (based on the amount of ethyl vanillate).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([C:8]([CH3:11])([CH3:10])[CH3:9])[CH:5]=[CH:4][C:3]=1[O:12][CH2:13][P:14]([O:19]CC)([O:16]CC)=[O:15].C[Si](Br)(C)C>>[NH2:1][C:2]1[CH:7]=[C:6]([C:8]([CH3:9])([CH3:10])[CH3:11])[CH:5]=[CH:4][C:3]=1[O:12][CH2:13][P:14]([OH:19])([OH:16])=[O:15]
Reactant: CCOP(=O)(COc1ccc(C(C)(C)C)cc1N)OCC
Agent: C[Si](C)(C)Br
Product: CC(C)(C)c1ccc(OCP(=O)(O)O)c(N)c1

Procedure:
The compound 2-amino-4-tert-butyl-1-diethylphosphonomethoxybenzene was deesterified with TMSBr as described in Step D, Example 1, to provide the title compound (no. 15.01) as a solid. HPLC Rt=4.45 min; negative ion electrospray MS M−1 found: 258.
Reaction SMILES: [C:1]([C:3]([C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][C:11]=1[Cl:17])([CH2:6][CH2:7][CH2:8][CH3:9])[CH2:4][OH:5])#[N:2].[CH3:18][S:19](Cl)(=[O:21])=[O:20].C1C=CC=CC=1>C(N(CC)CC)C>[CH3:18][S:19]([O:5][CH2:4][C:3]([C:1]#[N:2])([C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][C:11]=1[Cl:17])[CH2:6][CH2:7][CH2:8][CH3:9])(=[O:21])=[O:20]
Reactant: CS(=O)(=O)Cl
Reactant: CCCCC(C#N)(CO)c1ccc(Cl)cc1Cl
Solvent: CCN(CC)CC
Solvent: c1ccccc1
Product: CCCCC(C#N)(COS(C)(=O)=O)c1ccc(Cl)cc1Cl
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A mixture of 2-cyano-2 -(2,4-dichlorophenyl)hexan-1ol (5.6g., 0.02 mole) and methane sulfonyl chloride (2.9g., 0.025 mole) in 200 ml. of benzene is added dropwise at 10° C., 2.8g. (0.027) of triethylamine. The reaction mixture is stirred at room temperature for 30 minutes and then heated on a steam bath for another 30 minutes. The precipitate formed is filtered and the filtrate is washed with dilute hydrochloric acid, water, saturated sodium bicarbonate solution, saturated sodium chloride solution and dried over magnesium sulfate. The solvent is evaporated to give 6.3g. of product.
Reaction SMILES: [CH3:1][N:2](C=O)C.Br[C:7]1[CH:16]=[C:15]2[C:10]([CH2:11][CH2:12][C:13](=[O:17])[NH:14]2)=[CH:9][CH:8]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CN(CCN(C)C)C>[C-]#N.[Zn+2].[C-]#N.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CCOC(C)=O.C(Cl)(Cl)Cl>[O:17]=[C:13]1[CH2:12][CH2:11][C:10]2[C:15](=[CH:16][C:7]([C:1]#[N:2])=[CH:8][CH:9]=2)[NH:14]1
Reactant: CN(C)C=O
Reactant: O=C1CCc2ccc(Br)cc2N1
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: CN(C)CCN(C)C
Solvent: CCOC(C)=O
Solvent: ClC(Cl)Cl
Product: N#Cc1ccc2c(c1)NC(=O)CC2
Temperature: 180 °C
Reaction time: 0.08 h

Procedure:
To a DMF solution (14.5 mL) of the compound (3.00 g) obtained in Step 1-2, zinc cyanide (1.04 g), Pd2(dba)3 (122 mg), Xantphos (154 mg) and TMEDA (590 μL) were added and the mixture was stirred under microwave irradiation (180° C.) for 5 minutes. To the reaction mixture, CHCl3 was added and the mixture was filtrated by Celite and washed with DMF. The filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (silica gel 60 N, mobile phase: EtOAc/hexane=50/50 to 100/0; v/v). To the solid substance obtained, EtOAc was added at room temperature and the mixture was stirred for 30 minutes. A solid substance was obtained by filtration and washed with EtOAc to obtain 2-oxo-1,2,3,4-tetrahydroquinoline-7-carbonitrile (15.5 g, a light yellow solid).
Reaction SMILES: [CH:1]([CH:4]1[CH2:12][C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:13](=[CH2:17])[C:14]([OH:16])=[O:15])[CH:10]=2)[CH2:5]1)([CH3:3])[CH3:2].OCC([NH3+])(CO)CO>C(O)C.[Pt](=O)=O>[CH:1]([CH:4]1[CH2:12][C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH:13]([CH3:17])[C:14]([OH:16])=[O:15])[CH:10]=2)[CH2:5]1)([CH3:3])[CH3:2]
Reactant: C=C(C(=O)O)c1ccc2c(c1)CC(C(C)C)C2
Agent: O=[Pt]=O
Agent: [NH3+]C(CO)(CO)CO
Solvent: CCO
Product: CC(C(=O)O)c1ccc2c(c1)CC(C(C)C)C2

Procedure:
A solution of 1.7 g of 2-isopropyl-α-methylene-5-indanacetic acid in 300 cc of ethanol is hydrogenated at room temperature with the addition of 50 mg of platinum(IV) oxide. After filtering off the catalyst, removing the solvent by evaporation and chromatographing the resulting oil, 2-isopropyl-α-methyl-5-indanacetic acid, having a M.P. of 83°-86°, is obtained. The (1,3-dihydroxy-2-hydroxymethyl-2-propyl)ammonium salt of the title compound has a M.P. of 140°-141° (from methanol/ether).
Reaction SMILES: [H-].[H-].[H-].[H-].[Li+].[Al+3].C([O:9][C:10](=O)[CH2:11][C:12]1[C:21]2[C:16](=[C:17]([O:22][CH3:23])[CH:18]=[CH:19][CH:20]=2)[CH:15]=[CH:14][CH:13]=1)C.[O-]S([O-])(=O)=O.[Na+].[Na+]>CCOCC>[OH:9][CH2:10][CH2:11][C:12]1[C:21]2[C:16](=[C:17]([O:22][CH3:23])[CH:18]=[CH:19][CH:20]=2)[CH:15]=[CH:14][CH:13]=1
Reactant: CCOC(=O)Cc1cccc2c(OC)cccc12
Agent: O=S(=O)([O-])[O-]
Agent: [Al+3]
Agent: [H-]
Solvent: CCOCC
Product: COc1cccc2c(CCO)cccc12
Reaction time: 2 h

Procedure:
To a stirred suspension of 3 g (0.08 mole) of LiAlH4 in 100 mL of dry Et2O, a solution of 30 g (0.12 mole) of ethyl-5-methoxy-naphthalene-1-acetate in 400 mL of dry Et2O was added over 135 mins under N2. The mixture was stirred for 2 h, cooled in ice, and decomposed by dropwise addition of 20 mL of satd. aq. Na2SO4 solution. The precipitate was filtered off and washed with Et2O. After evaporation of the solvent a crystalline product remained that was stirred with cold hexane. The alcohol (21.95 g, 90.5%) melted at 61°-62° C.