Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]([C:3]1[CH:4]=[C:5]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:6](=[O:13])[N:7]2[C:12]=1[CH:11]=[CH:10][CH:9]=[CH:8]2)=O.[Cl-].[F:20][C:21]([F:35])([F:34])[C:22]1[CH:27]=[CH:26][C:25]([CH:28]2[CH2:33][CH2:32][NH2+:31][CH2:30][CH2:29]2)=[CH:24][CH:23]=1.C(N(CC)CC)C.C(O)(=O)C.C([BH3-])#N>ClC(Cl)C>[O:13]=[C:6]1[N:7]2[C:12]([CH:11]=[CH:10][CH:9]=[CH:8]2)=[C:3]([CH2:1][N:31]2[CH2:32][CH2:33][CH:28]([C:25]3[CH:26]=[CH:27][C:22]([C:21]([F:20])([F:34])[F:35])=[CH:23][CH:24]=3)[CH2:29][CH2:30]2)[CH:4]=[C:5]1[C:14]([O:16][CH2:17][CH3:18])=[O:15]
Reactant: FC(F)(F)c1ccc(C2CC[NH2+]CC2)cc1
Reactant: CCOC(=O)c1cc(C=O)c2ccccn2c1=O
Agent: [BH3-]C#N
Agent: [Cl-]
Solvent: CC(=O)O
Solvent: CCN(CC)CC
Solvent: CC(Cl)Cl
Product: CCOC(=O)c1cc(CN2CCC(c3ccc(C(F)(F)F)cc3)CC2)c2ccccn2c1=O
Temperature: 120 °C

Procedure:
In a 2-5 mL Emrys™ process vial, the ethyl 1-formyl-4-oxo-4H-quinolizine-3-carboxylate (599 mg, 2.44 mmol) and the 4-[4-(trifluoromethyl)phenyl]piperidinium chloride (672 mg, 2.53 mmol) were diluted with 4.9 mL of dichloroethane, which was neutralized with the addition of triethylamine (0.41 mL, 2.93 mmol). To the stirring mixture was added glacial acetic acid (0.84 mL, 14.7 mmol) and resin-bound MP-cyanoborohydride (307 mg, 4.89 mmol). The mixture was heated via Emrys Optimizer™ microwave to 120° C. for 20 minutes. After filtration, the filtrate was washed with water (3×20). The organic layer was dried over sodium sulfate, filtered, concentrated, and purified by silica gel chromatography eluting with 30-80% EtOAc in hexanes to provide ethyl 4-oxo-1-({4-[4-(trifluoromethyl)phenyl]piperidin-1-yl}methyl)-4H-quinolizine-3-carboxylate.
Reaction SMILES: [F:1][C:2]1[C:11]2[CH:12]([CH2:14][CH2:15][NH:16][CH2:17][C@H:18]3[O:22][C:21](=[O:23])[N:20]([C:24]4[CH:25]=[CH:26][C:27]5[S:32][CH2:31][C:30](=[O:33])[NH:29][C:28]=5[CH:34]=4)[CH2:19]3)[CH2:13][N:9]3[C:10]=2[C:5]([CH:6]=[CH:7][C:8]3=[O:35])=[CH:4][CH:3]=1.[Si:36]([O:43][CH2:44][CH2:45][CH:46]=O)([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:38])[CH3:37]>>[C:39]([Si:36]([CH3:38])([CH3:37])[O:43][CH2:44][CH2:45][CH2:46][N:16]([CH2:17][CH:18]1[O:22][C:21](=[O:23])[N:20]([C:24]2[CH:25]=[CH:26][C:27]3[S:32][CH2:31][C:30](=[O:33])[NH:29][C:28]=3[CH:34]=2)[CH2:19]1)[CH2:15][CH2:14][CH:12]1[C:11]2=[C:10]3[C:5](=[CH:4][CH:3]=[C:2]2[F:1])[CH:6]=[CH:7][C:8](=[O:35])[N:9]3[CH2:13]1)([CH3:42])([CH3:41])[CH3:40]
Reactant: CC(C)(C)[Si](C)(C)OCCC=O
Reactant: O=C1CSc2ccc(N3C[C@@H](CNCCC4Cn5c(=O)ccc6ccc(F)c4c65)OC3=O)cc2N1
Product: CC(C)(C)[Si](C)(C)OCCCN(CCC1Cn2c(=O)ccc3ccc(F)c1c32)CC1CN(c2ccc3c(c2)NC(=O)CS3)C(=O)O1
Yield: 75 %

Procedure:
Starting from the compound of Example 10 and 3-(tert-butyldimethylsilyloxy)-propionaldehyde and using procedure E, the title compound was obtained as a colourless solid (101 mg; 75% yield).
Reaction SMILES: O=[C:2]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH2:3][NH:4][C:5]([CH:7]1[CH2:12][CH:11]([CH3:13])[CH2:10][CH2:9][CH:8]1[CH:14]([CH3:16])[CH3:15])=[O:6].N.[BH3-]C#[N:26].[Na+].C([O-])(O)=O.[Na+]>C(OCC)(=O)C.C(O)(=O)C>[NH2:26][CH:2]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH2:3][NH:4][C:5]([CH:7]1[CH2:12][CH:11]([CH3:13])[CH2:10][CH2:9][CH:8]1[CH:14]([CH3:16])[CH3:15])=[O:6]
Reactant: CC1CCC(C(C)C)C(C(=O)NCC(=O)c2ccccc2)C1
Reactant: [BH3-]C#N
Agent: N
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: CC1CCC(C(C)C)C(C(=O)NCC(N)c2ccccc2)C1
Reaction time: 1.33 h
Yield: 93.4 %

Procedure:
A 25 mL microwave reaction vessel equipped with a stir bar was charged with 2-isopropyl-5-methyl-cyclohexanecarboxylic acid (2-oxo-2-phenyl-ethyl)-amide (80 mg) and ammonia (1.5 mL, 7 M in methanol). A drop of acetic acid and NaCNBH3 (20 mg) were added to the reaction mixture and subjected to microwave at 80° C. for 80 min. The residue was taken up in ethyl acetate (30 mL) and saturated NaHCO3 (aq.) (30 mL). The heterogeneous mixture was transferred to a separatory funnel where the aqueous phase was separated and re-extracted with ethyl acetate (2×10 mL). The organic phases were combined and washed with sat NaHCO3 (3×10 mL), H2O (10 mL), brine (10 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give a solid (75 mg).
Reaction SMILES: S(Cl)([Cl:3])=O.[C:5]([NH:8][C:9]1[N:14]=[C:13]([CH2:15]O)[CH:12]=[CH:11][N:10]=1)(=[O:7])[CH3:6]>C(Cl)Cl>[C:5]([NH:8][C:9]1[N:14]=[C:13]([CH2:15][Cl:3])[CH:12]=[CH:11][N:10]=1)(=[O:7])[CH3:6]
Reactant: CC(=O)Nc1nccc(CO)n1
Reactant: O=S(Cl)Cl
Solvent: ClCCl
Product: CC(=O)Nc1nccc(CCl)n1
Yield: 18 %

Procedure:
Thionyl chloride (0.18 mL, 2.4 mmol) was added to a suspension of 2-acetylamino-4-hydroxymethylpyrimidine (290 mg, 1.7 mmol, Reference Compound No. 4-3) in anhydrous methylene chloride (10 mL) at room temperature, and the mixture was stirred for 30 minutes. The solvent was evaporated under reduced pressure, then water (50 mL) and ethyl acetate (100 mL) were added thereto and the mixture was separated into the organic layer and the aqueous layer, and the aqueous layer was extracted twice with ethyl acetate (50 mL). The whole organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to give 68 mg of the title Reference Compound as a yellow solid (Yield: 18%).
Reaction SMILES: [CH2:1]([C:3]1[S:7][C:6]([C:8]([OH:10])=O)=[C:5]2[CH2:11][CH2:12][C:13]([CH3:16])([CH3:15])[CH2:14][C:4]=12)[CH3:2].[CH3:17][Li]>C(OCC)C>[CH2:1]([C:3]1[S:7][C:6]([C:8](=[O:10])[CH3:17])=[C:5]2[CH2:11][CH2:12][C:13]([CH3:16])([CH3:15])[CH2:14][C:4]=12)[CH3:2]
Reactant: [Li]C
Reactant: CCc1sc(C(=O)O)c2c1CC(C)(C)CC2
Solvent: CCOCC
Product: CCc1sc(C(C)=O)c2c1CC(C)(C)CC2
Reaction time: 0.25 h

Procedure:
To a solution of 3-ethyl-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophene-1-carboxylic acid (2.10 g, 8.81 mmol) in diethyl ether (100 mL), a solution of methyllithium (11 mL, 1.6 M solution in diethyl ether) is added at rt. The pale yellow solution is stirred at rt for 15 min before another portion of methyllithium (2 mL) is added. Stirring is continued for 15 min, a further portion of methyllithium (1 mL) is added, and the mixture is again stirred for 15 min at rt. The reaction is quenched with water. The organic layer is separated, washed once more with water, dried over MgSO4 and evaporate. The crude product is purified by CC on silica gel eluting with heptane:EA 7:3 to give 1-(3-ethyl-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophen-1-yl)-ethanone (1.65 g) as a pale yellow solid; LC-MS: tR=1.00 min, [M+1]=237.15; 1H NMR (CDCl3): δ 3.03 (t, J=7.0 Hz, 2H), 2.73 (q, J=7.6 Hz, 2H), 2.47 (s, 3H), 2.31 (s, 2H), 1.55 (t, J=7.0 Hz, 2H), 1.28 (t, J=7.6 Hz, 3H), 0.97 (s, 6H).
Reaction SMILES: [CH3:1][CH:2]1[C:13]2[C:14]3[C:6](=[CH:7][N:8]([S:23]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)(=[O:25])=[O:24])[C:9]=3[CH:10]=[CH:11][C:12]=2OS(C(F)(F)F)(=O)=O)[CH2:5][CH2:4][N:3]1C(OC(C)(C)C)=O.N#N.C([O-])=O.[NH4+]>CO.[Pd]>[CH3:1][CH:2]1[C:13]2[C:14]3[C:6](=[CH:7][N:8]([S:23]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)(=[O:25])=[O:24])[C:9]=3[CH:10]=[CH:11][CH:12]=2)[CH2:5][CH2:4][NH:3]1
Reactant: CC1c2c(OS(=O)(=O)C(F)(F)F)ccc3c2c(cn3S(=O)(=O)c2ccccc2)CCN1C(=O)OC(C)(C)C
Agent: [Pd]
Agent: N#N
Agent: O=C[O-]
Solvent: CO
Product: CC1NCCc2cn(S(=O)(=O)c3ccccc3)c3cccc1c23
Temperature: 25 °C
Reaction time: 48 h

Procedure:
A solution of tert-butyl 6-methyl-1-(phenylsulfonyl)-7-{[(trifluoromethyl)sulfonyl]oxy}-1,3,4,6-tetrahydro-5H-azepino[5,4,3-cd]indole-5-carboxylate, Intermediate 16 (16 mg, 0.028 mmol) in MeOH (4 mL) and was carefully added to a 16 mm test tube containing Pd/C (35 mg). The suspension was purged with N2, ammonium formate (88 mg, 1.4 mmol) was added in one portion, the mixture was N2-purged once more and the mixture was stirred at room temperature over two days. The detriflated intermediate was purified with preparative HPLC (ACE C8 5 mm, water containing 0.1% TFA —CH3CN). The pure fraction was evaporated at reduced pressure, DCM/TFA 50/50, (1 mL) was added and the mixture was left at room temperature for one hour. The crude was purified by preparative HPLC (Xterra C18, 10 mM NH4CO3 (pH 10)-CH3CN) to give 0.8 mg of the title compound as a white oil. MS (ESI) m/z 326 [M+H]+.
Reaction SMILES: [Cl:1][C:2]([Cl:50])([Cl:49])[C:3]([O:6][C:7]([N:9]1[C@H:14]2[C:15]([C:37]([O:39]CC)=[O:38])=[C:16]([C:18]3[CH:19]=[N:20][C:21]([O:24][CH2:25][CH2:26][O:27][C:28]4[C:33]([Cl:34])=[CH:32][C:31]([CH3:35])=[CH:30][C:29]=4[Cl:36])=[CH:22][CH:23]=3)[CH2:17][C@@H:10]1[CH2:11][N:12]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:13]2)=[O:8])([CH3:5])[CH3:4].[OH-].[Na+]>CCO>[Cl:50][C:2]([Cl:1])([Cl:49])[C:3]([O:6][C:7]([N:9]1[C@H:14]2[C:15]([C:37]([OH:39])=[O:38])=[C:16]([C:18]3[CH:19]=[N:20][C:21]([O:24][CH2:25][CH2:26][O:27][C:28]4[C:33]([Cl:34])=[CH:32][C:31]([CH3:35])=[CH:30][C:29]=4[Cl:36])=[CH:22][CH:23]=3)[CH2:17][C@@H:10]1[CH2:11][N:12]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:13]2)=[O:8])([CH3:4])[CH3:5]
Reactant: CCOC(=O)C1=C(c2ccc(OCCOc3c(Cl)cc(C)cc3Cl)nc2)C[C@@H]2CN(C(=O)OC(C)(C)C)C[C@H]1N2C(=O)OC(C)(C)C(Cl)(Cl)Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: Cc1cc(Cl)c(OCCOc2ccc(C3=C(C(=O)O)[C@H]4CN(C(=O)OC(C)(C)C)C[C@@H](C3)N4C(=O)OC(C)(C)C(Cl)(Cl)Cl)cn2)c(Cl)c1
Temperature: 80 °C
Reaction time: 3 h

Procedure:
Compound C5 (1.02 g, 1.3 mmol) was dissolved in EtOH (14 mL), and aq. 1M NaOH (6 mL) was added. The mixture was heated to 80° C., and stirred at this temperature for 3 h. The mixture was allowed to cool to rt, and the solvents were partially removed under reduced pressure. The residue was mixed with EtOAc, and this mixture was acidified with aq. 1M HCl. The phases were partitioned, and the aq. layer was extracted with EtOAc (2×). The combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Drying under high vacuum yielded the crude title compound mixed with (rac.)-(1R*,5S*)-7-{6-[2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy]-pyridin-3-yl}-3,9-diaza-bicyclo[3.3.1]non-7-ene-3,6,9-tricarboxylic acid 3-tert-butyl ester 9-(2,2,2-trichloro-1,1-dimethyl-ethyl) ester (864 mg, 87%), which was used further without purification. LC-MS: tR=1.15 min; ES+: 768.23.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[N:10]1[CH2:19][C:18]2[C:13](=[N:14][C:15]([NH:20][C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)=[N:16][CH:17]=2)[N:12]([C@:28](O[SiH3])([CH3:46])[C:29](C2C=CC=CC=2)(C2C=CC=CC=2)C(C)(C)C)[C:11]1=[O:49].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[O:68]1CCCC1>>[F:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[N:10]1[CH2:19][C:18]2[C:13](=[N:14][C:15]([NH:20][C:21]3[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=3)=[N:16][CH:17]=2)[N:12]([C@@H:28]([CH3:46])[CH2:29][OH:68])[C:11]1=[O:49]
Reactant: C1CCOC1
Reactant: COc1ccc(N2Cc3cnc(Nc4ccc(F)cc4)nc3N([C@@](C)(O[SiH3])C(c3ccccc3)(c3ccccc3)C(C)(C)C)C2=O)c(F)c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Product: COc1ccc(N2Cc3cnc(Nc4ccc(F)cc4)nc3N([C@@H](C)CO)C2=O)c(F)c1
Reaction time: 4 h

Procedure:
(S)-3-(2-Fluoro-4-methoxy-phenyl)-7-(4-fluoro-phenylamino)-1-(2-tert-butyl-diphenyl-silanyloxy-1-methyl-ethyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one (0.33 g, 0.46 mmol) was dissolved in anhydrous tetrahydrofuran (3.5 mL) and treated with tetrabutylammonium fluoride (1.0 M in tetrahydrofuran, 1.90 mL, 1.90 mmol) (Aldrich). The reaction was stirred in a water bath that was maintained in the 25–35° C. range. The reaction was complete after 4 hours and was concentrated. The residue was redissolved in ethyl acetate and washed with water and brine. The organic phase was dried over anhydrous sodium sulfate and concentrated. Purification by flash chromatography (Biotage 40S, 75:25 ethyl acetate-hexanes) followed by crystallization from ethyl acetate-hexanes gave (S)-(+)-3-(2-fluoro-4-methoxy-phenyl)-7-(4-fluoro-phenylamino)-1-(2-hydroxy-1-methyl-ethyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one as a white solid. (Yield 0.18 g, 83.5%). Melting Point: 173–177° C.
Reaction SMILES: [OH:1][C@H:2]([CH3:8])[CH2:3][C:4]([O:6][CH3:7])=[O:5].N1C=CN=C1.[Si:14](Cl)([C:27]([CH3:30])([CH3:29])[CH3:28])([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>ClCCl>[CH3:7][O:6][C:4](=[O:5])[CH2:3][C@H:2]([O:1][Si:14]([C:27]([CH3:30])([CH3:29])[CH3:28])([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH3:8]
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Reactant: COC(=O)C[C@@H](C)O
Agent: c1c[nH]cn1
Solvent: ClCCl
Product: COC(=O)C[C@@H](C)O[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Temperature: 25 °C
Reaction time: 4.5 h

Procedure:
Methyl (R)-(−)-3-hydroxybutyrate (0.31 g, 2.61 mmol) (Aldrich) was dissolved in dichloromethane (3.5 mL, dried over molecular sieves). Imidazole (0.25 g, 3.66 mmol) (Aldrich) was added. When all had dissolved, tert-butyldiphenylsilyl chloride (0.69 mL, 2.63 mmol) (Aldrich) was added dropwise and the mixture was stirred at room temperature for 4.5 hours. The reaction mixture was diluted with additional dichloromethane, washed with water (2×) and brine, dried over anhydrous sodium sulfate, filtered and concentrated. Purification by flash chromatography (Biotage 40M, 5:95 ethyl acetate-hexanes) gave (R)-3-(tert-butyl-diphenyl-silanyloxy)-butyric acid methyl ester. (Yield 0.85 g, 91.2%).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:22])[CH2:5][C:6]1[C:11]([N+:12]([O-])=O)=[CH:10][N:9]=[C:8]([N:15]2[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][CH2:16]2)[CH:7]=1)[CH3:2].[H][H]>CO.[Pd]>[CH2:1]([O:3][C:4](=[O:22])[CH2:5][C:6]1[C:11]([NH2:12])=[CH:10][N:9]=[C:8]([N:15]2[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][CH2:16]2)[CH:7]=1)[CH3:2]
Reactant: CCOC(=O)Cc1cc(N2CCN(C)CC2)ncc1[N+](=O)[O-]
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: CCOC(=O)Cc1cc(N2CCN(C)CC2)ncc1N
Reaction time: 2.5 h

Procedure:
[2-(4-Methyl-piperazin-1-yl)-5-nitro-pyridin-4-yl]-acetic acid ethyl ester (2.78 g, 9.02 mmol) is dissolved in MeOH (28 ml). Palladium on carbon (10%, 96 mg, 0.90 mmol) is added, and the reaction flask is connected to a balloon filled with hydrogen. After vigorous stirring for 2.5 h, TLC analysis indicated complete conversion. The reaction mixture is filtered, the organic solvent removed, and the residue purified by FCC (CH2Cl2/MeOH, gradient from 97:3 to 70:30) to yield [5-amino-2-(4-methyl-piperazin-1-yl)-pyridin-4-yl]-acetic acid ethyl ester. 1H NMR (CDCl3, 400 MHz): δ 1.27 (t, J=7 Hz, 3H), 2.35 (s, 3H), 2.54 (m, 4H), 3.40 (m, 4H), 3.55 (s, 2H), 3.62 (s, broad, 2H), 4.16 (q, J=7 Hz, 2H), 6.50 (s, 1H), 7.79 (s, 1H). ES+−MS: 279.3 [M+H]+.
Reaction SMILES: [CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[NH:17][C:16]([C:21]([OH:23])=O)=[CH:15]3)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].C1(N2CCN(C(C3C=C4C(=CC=3)NC(C(N3CCS(=O)(=O)CC3)=O)=C4)=O)CC2)CCCC1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[O:78]1[C:82]2([CH2:87][CH2:86][NH:85][CH2:84][CH2:83]2)[O:81][CH2:80][CH2:79]1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[O:78]1[C:82]2([CH2:87][CH2:86][N:85]([C:21]([C:16]3[NH:17][C:18]4[C:14]([CH:15]=3)=[CH:13][C:12]([C:10]([N:7]3[CH2:8][CH2:9][N:4]([CH:1]([CH3:2])[CH3:3])[CH2:5][CH2:6]3)=[O:11])=[CH:20][CH:19]=4)=[O:23])[CH2:84][CH2:83]2)[O:81][CH2:80][CH2:79]1
Reactant: C1CC2(CCN1)OCCO2
Reactant: CC(C)N1CCN(C(=O)c2ccc3[nH]c(C(=O)O)cc3c2)CC1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Agent: O=C(c1ccc2[nH]c(C(=O)N3CCS(=O)(=O)CC3)cc2c1)N1CCN(C2CCCC2)CC1
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)N1CCN(C(=O)c2ccc3[nH]c(C(=O)N4CCC5(CC4)OCCO5)cc3c2)CC1
Yield: 64 %

Procedure:
The title compound was synthesized in analogy to example 1, from 5-(4-isopropyl-piperazine-1-carbonyl)-1H-indole-2-carboxylic acid 1:1 hydrochlorid (example 1, intermediate b), O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (commercially available), 1,4-dioxa-8-azaspiro[4.5]decane (commercially available) and N,N-diisopropylethylamine in N,N-dimethylformamide, to give the desired product as a light brown solid (64%).
Reaction SMILES: C([Li])CCC.C(NC(C)C)(C)C.[N:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH3:19].[CH:20]([C:22]1[CH:27]=[CH:26][C:25]([C:28]([O:30][CH3:31])=[O:29])=[CH:24][CH:23]=1)=[O:21].[Cl-].[NH4+]>C1COCC1.CCCCCC>[OH:21][CH:20]([C:22]1[CH:23]=[CH:24][C:25]([C:28]([O:30][CH3:31])=[O:29])=[CH:26][CH:27]=1)[CH2:19][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][N:13]=1
Reactant: Cc1ccccn1
Reactant: COC(=O)c1ccc(C=O)cc1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCCCCC
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Product: COC(=O)c1ccc(C(O)Cc2ccccn2)cc1
Temperature: 0 °C
Reaction time: 0.08 h
Yield: 5.4 %

Procedure:
With cooling with ice, a hexane solution (48 mL) of 2.6 N n-butyllithium was added to a THF solution (300 mL) of diisopropylamine (18 mL), stirred at 0° C. for 5 minutes, and then cooled to −78° C. Next, 2-picoline (10 g) was dropwise added thereto, and stirred at that temperature for 30 minutes. THF solution (100 mL) of methyl 4-formylbenzenecarboxylate (17.6 g) was added thereto, and stirred at −78° C. for 30 minutes and then at room temperature for 4 hours. Aqueous saturated ammonium chloride solution was added to the reaction liquid, and extracted with ethyl acetate. The organic layer was washed with aqueous saturated ammonium chloride solution and saturated saline water, and dried with anhydrous sodium sulfate. The solvent was evaporated off under reduced pressure, and the resulting residue was purified through silica gel column chromatography (hexane/ethyl acetate=2/1) to obtain the entitled compound (1.5 g) as a colorless solid.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH3:12])[CH:6]=[N:5]2.FC1[C:15]([CH:24]([CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])CC)=NC2C(N=1)=CC=CC=2>>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH2:12][CH2:15][C:24]#[C:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[CH:6]=[N:5]2
Reactant: Cc1cnc2cc(F)ccc2n1
Reactant: CCC(C[Si](C)(C)C)c1nc2ccccc2nc1F
Product: C[Si](C)(C)C#CCCc1cnc2cc(F)ccc2n1

Procedure:
The title compound was prepared in accordance with the general method of Example 118(A), from 6-fluoro-2-methyl-quinoxaline (100 mg, 0.62 mmol). The crude residue was purified by flash chromatography (cyclohexane/AcOEt 4:1) to yield 66 mg (0.24 mmol, 39%) of 6 fluoro-2-(4-trimethylsilanyl-but-3-yl)-quinoxaline as an orange oil.
Reaction SMILES: Cl.[NH2:2][C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:12]=1[SH:13])=[CH:10][CH:9]=[CH:8][CH:7]=2.[CH:14](=O)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C(O)C>[C:15]1([C:14]2[S:13][C:12]3[C:11]4[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=4[N:5]=[CH:4][C:3]=3[N:2]=2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: Nc1cnc2ccccc2c1S
Reactant: O=Cc1ccccc1
Agent: Cl
Solvent: CCO
Product: c1ccc(-c2nc3cnc4ccccc4c3s2)cc1

Procedure:
A mixture of 20.52 g (0.1 mole) of 3-amino-4-mercapto-quinoline-hydrochloride, 10.61 g (0.1 mole) of freshly distilled benzaldehyde and 200 ml of ethanol is refluxed for 2 hours, whereupon air is bubbled through the reaction mixture for several days. The precipitated crystals are filtered and recrystallized from ethanol. Thus 13.5 g of 2-phenyl-thiazolo[4,5-c]quinoline are obtained. The melting point of this product is identical with that of the compound prepared according to Example 5.
Reaction SMILES: [CH2:1]([CH:3]([CH2:24][CH2:25][CH2:26][CH3:27])[CH2:4][C:5]1([CH2:16][CH:17]([CH2:22][CH3:23])[CH2:18][CH2:19][CH2:20][CH3:21])[C:15]2[CH:14]=[CH:13][S:12][C:11]=2[C:7]2[S:8][CH:9]=[CH:10][C:6]1=2)[CH3:2].[Li]CCCC.[CH2:33]([Sn:37](Cl)([CH2:42]CCC)[CH2:38]CCC)CCC.CCCCCC>C1COCC1>[CH2:1]([CH:3]([CH2:24][CH2:25][CH2:26][CH3:27])[CH2:4][C:5]1([CH2:16][CH:17]([CH2:22][CH3:23])[CH2:18][CH2:19][CH2:20][CH3:21])[C:6]2[CH:10]=[C:9]([Sn:37]([CH3:42])([CH3:38])[CH3:33])[S:8][C:7]=2[C:11]2[S:12][C:13]([Sn:37]([CH3:42])([CH3:38])[CH3:33])=[CH:14][C:15]1=2)[CH3:2]
Reactant: CCCC[Sn](Cl)(CCCC)CCCC
Reactant: CCCCC(CC)CC1(CC(CC)CCCC)c2ccsc2-c2sccc21
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CCCCC(CC)CC1(CC(CC)CCCC)c2cc([Sn](C)(C)C)sc2-c2sc([Sn](C)(C)C)cc21
Temperature: -78 °C
Reaction time: 1 h
Yield: 94 %

Procedure:
The 4,4-bis(2-ethylhexyl)-4H-cyclopenta[2,1-b:3,4-b′]dithiophene (3.0 g, 7.45 mmol) prepared above was dissolved in anhydrous THF (20 mL) and kept at −78° C. under nitrogen flow. Then, n-BuLi (19 mL, 29.8 mmol, 2.5 M in hexane) was slowly added over 30 minutes. Subsequently, after stirring at −78° C. for 1 hour, tributyltin chloride (7.4 g, 37.1 mmol) was added and reaction was performed at room temperature for 17 hours. The resulting product was extracted with ether and distilled water, dried with anhydrous MgSO4 and filtered under reduced pressure. The final product 4,4-bis(2-ethylhexyl)-2,6-bis(trimethylstannyl)-4H-cyclopenta[2,1-b:3,4-b′]dithiophene (5.1 g, yield: 94%) was obtained by column chromatography (neutral alumina, n-hexane). 1H NMR (300 MHz, CDCl3, ppm): δ 7.01-6.88 (m, 2H), 1.93-1.76 (m, 4H), 1.04-0.81 (m, 18H), 0.74 (t, 6H), 0.59 (t, 6H), 0.49-0.22 (m, 18H).
Reaction SMILES: C[O:2][C:3](=O)[C@H:4]([NH:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1.B.[Li].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1>[C:16]([O:15][C:13](=[O:14])[NH:12][C@H:4]([C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1)[CH2:3][OH:2])([CH3:19])([CH3:17])[CH3:18]
Reactant: COC(=O)[C@H](NC(=O)OC(C)(C)C)c1ccc(O)cc1
Agent: B
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [Li]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N[C@@H](CO)c1ccc(O)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
(R)-tert-Butoxycarbonylamino-(4-hydroxy-phenyl)-acetic acid methyl ester (10 mmol), Lithium Boron hydride (1.089 g, 50 mmol) and THF (50 ml) were combined and stirred at room temperature overnight. Ice (20 ml) was added into the reaction mixture with stirring. Saturated citric acid was then added dropwise until no more bubbles were generated. The reaction mixture was transferred to a separatory funnel. The aqueous layer was extracted with ethyl acetate (3×30 ml). The combined organic layers were washed with saturated NH4Cl and water sequentially, then dried over MgSO4, filtered and concentrated to give a white crude solid (2.92 g, crude product) with some impurity: 1H NMR (400 MHz, MeOD) δ ppm 7.14 (d, J=8.6 Hz, 2H), 6.76 (d, J=8.6 Hz, 2H), 4.56 (m, 1H), 3.63 (m, 2H), 1.43 (s, 9H); LCMS (ESI) m/e 254.1 [(M+H)+, calcd for C13H20NO4 254.3].
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([C:14]([NH:16][NH2:17])=[O:15])[C:7]2[C:12]([CH:13]=1)=[CH:11][CH:10]=[CH:9][CH:8]=2)([O-:3])=[O:2].[C:18]([C:21]1[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=1)(=O)[CH3:19].C(O)C>C(O)(=O)C.O1CCCC1>[N:24]1[CH:25]=[CH:26][C:21]([C:18](=[N:17][NH:16][C:14]([C:6]2[C:7]3[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH:13]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)=[O:15])[CH3:19])=[CH:22][CH:23]=1
Reactant: NNC(=O)c1cc([N+](=O)[O-])cc2ccccc12
Reactant: CC(=O)c1ccncc1
Solvent: C1CCOC1
Solvent: CCO
Solvent: CC(=O)O
Product: CC(=NNC(=O)c1cc([N+](=O)[O-])cc2ccccc12)c1ccncc1
Temperature: 25 °C
Yield: 87.4 %

Procedure:
A mixture of 5.0 gm of (0.0216 mole) of 3-nitro-1-naphthalenecarboxylic acid hydrazide, 2.62 gm (0.0216 mole) of 4-acetylpyridine, 400 ml of ethanol, 100 ml of tetrahydrofuran, and 20 drops of glacial acetic acid was refluxed 10 hr. The hot solution was filtered. The filtrate was cooled to room temperature and then chilled. The product was collected, washed with Skellysolve B and dried to furnish 6.31 gm (87%) of the title compound having a melting point of 228.5° C.
Reaction SMILES: [C:1]1([CH2:7][C:8]([OH:19])([C:14]([O:16]CC)=[O:15])[C:9]([O:11]CC)=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CO.[Li+:22].[OH-]>CO>[Li+:22].[C:1]1([CH2:7][C:8]([OH:19])([C:14]([OH:16])=[O:15])[C:9]([O-:11])=[O:10])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CCOC(=O)C(O)(Cc1ccccc1)C(=O)OCC
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Product: O=C([O-])C(O)(Cc1ccccc1)C(=O)O

Procedure:
2 g of the ester are treated in MeOH with aqueous-methanol LiOH, as described above, to give 1.2 g of 3-phenyl-2-hydroxy-2-carboxy propanoic acid lithium salt, m.p. >300° C.:, I.R. 3400, 1640 cm-1 ; HNMR (D20) δ (TMS): 3,4 s, 7.2-7.35 m.