Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C@H:3]([NH:9][CH2:10][CH2:11][N:12]1[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][C:19]=3[C:21]([O:23]C)=[O:22])[CH:14]=[N:13]1)[CH2:2]2.O.[OH-].[Li+:27].O.CO>O1CCCC1>[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C@H:3]([NH:9][CH2:10][CH2:11][N:12]1[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][C:19]=3[C:21]([O-:23])=[O:22])[CH:14]=[N:13]1)[CH2:2]2.[Li+:27]
Reactant: COC(=O)c1cccc2cnn(CCN[C@@H]3CN4CCC3CC4)c12
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Solvent: C1CCOC1
Product: O=C([O-])c1cccc2cnn(CCN[C@@H]3CN4CCC3CC4)c12
Temperature: 25 °C
Reaction time: 17 h
Yield: 100.3 %

Procedure:
To a stirred solution of (S)-methyl 1-(2-(quinuclidin-3-ylamino)ethyl)-1H-indazole-7-carboxylate (370 mg, 1.12 mmol) from Step F above in tetrahydrofuran (5 mL) was added lithium hydroxide monohydrate (142 mg, 3.4 mmol), water (5 mL) and methanol (5 mL). The mixture was stirred at room temperature for 17 h and then concentrated under reduced pressure. The residue was co-evaporated with toluene (2×10 mL) and dried overnight under vacuum to afford crude lithium (S)-1-(2-(quinuclidin-3-ylamino)ethyl)-1H-indazole-7-carboxylate (360 mg, quantitative yield) which was used in the next step without further purification: 1H NMR (500 MHz, DMSO-d6) δ 7.97 (s, 1H), 7.53 (dd, J=8.0, 1.0 Hz, 1H), 7.32 (dd, J=6.5, 1.0 Hz, 1H), 6.96 (t, J=7.0 Hz, 1H), 4.85-4.75 (m, 2H), 4.50-3.50 (br s 2H), 2.90-2.70 (m, 3H), 2.65-2.45 (m, 4H), 2.11-2.07 (m, 1H), 1.68-1.65 (m, 2H), 1.51-1.46 (m, 1H), 1.31-1.26 (m, 1H), 1.10-1.06 (m, 1H); MS (ESI+) m/z 315 (M+H).
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]([CH3:12])=[CH2:11])[CH:5]=1)([CH3:3])=[CH2:2].C([Li:17])(CC)C.[CH3:18][CH2:19][CH2:20][CH2:21]CC>C1C=CC=CC=1>[Li:17][C:10]([C:6]1[CH:5]=[C:4]([CH:9]=[CH:8][CH:7]=1)[C:1]([CH3:3])=[CH2:2])([CH3:12])[CH2:11][CH:20]([CH3:21])[CH2:19][CH3:18]
Reactant: [Li]C(C)CC
Reactant: C=C(C)c1cccc(C(=C)C)c1
Reactant: CCCCCC
Solvent: c1ccccc1
Product: [Li]C(C)(CC(C)CC)c1cccc(C(=C)C)c1

Procedure:
316g (2 moles) of 1,3-diisopropenyl benzene (DIPB) and 400 ml benzene are charged to a dry, argon flushed, 12-liter 3-neck, round-bottom reaction flask. The reaction flask is equipped with a stirrer, thermometer, addition funnel and a dry ice-hexane cooling bath. The flask and contents are cooled to -20° and a premixed solution of 1670 ml of a 1.2N sec-butyllithium in hexane (2 moles) and 202g of TEA (2 moles) are added dropwise over a period of 2 hours. The temperature is held between -20° and -5° throughout the sec-butyllithium-TEA addition.
Reaction SMILES: [CH3:1][Mg]Br.[C:4]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH:12]1[CH2:24][CH:25]=[O:26])=[O:10])([CH3:7])([CH3:6])[CH3:5]>O1CCCC1.[Cl-].[NH4+]>[C:4]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][C@@H:12]1[CH2:24][C@@H:25]([OH:26])[CH3:1])=[O:10])([CH3:7])([CH3:6])[CH3:5].[C:4]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][C@@H:12]1[CH2:24][C@H:25]([OH:26])[CH3:1])=[O:10])([CH3:7])([CH3:6])[CH3:5]
Reactant: C[Mg]Br
Reactant: CC(C)(C)OC(=O)N1CCN(C(=O)OC(C)(C)C)C(CC=O)C1
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: C[C@@H](O)C[C@H]1CN(C(=O)OC(C)(C)C)CCN1C(=O)OC(C)(C)C
Product: C[C@H](O)C[C@H]1CN(C(=O)OC(C)(C)C)CCN1C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 5 h
Yield: 198.9 %

Procedure:
Add methylmagnesium bromide (3.61 mL, 10.8 mmol, 3M solution in diethyl ether) to a solution of 2-(2-oxoethyl)piperazine-1,4-dicarboxylic acid di-tert-butyl ester (3.036 g, 9.84 mmol) in tetrahydrofuran (30 mL) at 0° C. Warm the mixture to room temperature and stir for 5 hours. Dilute the mixture with saturated ammonium chloride and extract three times with ethyl acetate. Combine the organic layers, dry over sodium sulfate and concentrate under reduced pressure to give 2(S)-(2(S)-hydroxypropyl)piperazine-1,4-dicarboxylic acid di-tert-butyl ester and 2(S)-(2(R)-hydroxypropyl)piperazine-1,4-dicarboxylic acid di-tert-butyl ester (3.37 g, 99%) as a yellow oily solid: mass spectrum (APCI): m/z=245.2 (M+1-BOC).
Reaction SMILES: [C@@H:1]12[C:10](=[O:11])[O:9][C:7](=[O:8])[C@H:2]1[CH2:3][CH2:4][CH2:5][CH2:6]2.[CH3:12][O:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[O:20][CH3:21]>>[CH3:12][O:13][C:14]1[CH:19]=[C:18]([CH:17]=[CH:16][C:15]=1[O:20][CH3:21])[C:7]([C@@H:2]1[CH2:3][CH2:4][CH2:5][CH2:6][C@H:1]1[C:10]([OH:9])=[O:11])=[O:8]
Reactant: COc1ccccc1OC
Reactant: O=C1OC(=O)[C@H]2CCCC[C@H]12
Product: COc1ccc(C(=O)[C@@H]2CCCC[C@H]2C(=O)O)cc1OC

Procedure:
Prepared from trans-cyclohexane-1,2-dicarboxylic anhydride and 1,2-dimethoxybenzene as described for compound A M.p. 202°-205° C.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([N+:13]([O-:15])=[O:14])[C:5]([CH3:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:23][CH2:24][OH:25].C(OCC)(=O)C>C(#N)C.O>[OH:25][CH2:24][CH2:23][O:1][C:2]1[CH:3]=[C:4]([N+:13]([O-:15])=[O:14])[C:5]([CH3:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8]
Reactant: OCCBr
Reactant: COC(=O)c1cc(O)cc([N+](=O)[O-])c1C
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CC#N
Solvent: CCOC(C)=O
Product: COC(=O)c1cc(OCCO)cc([N+](=O)[O-])c1C
Temperature: 80 °C
Yield: 74.5 %

Procedure:
To a stirred solution of methyl 5-hydroxy-2-methyl-3-nitrobenzoate (1.5 g, 7.1 mmol) in ACN (15 mL), were added cesium carbonate (4.6 g, 14 mmol) and 2-bromoethanol (2.5 mL, 35 mmol). The resulting reaction mixture was heated at 80° C. overnight. On completion, the reaction mixture was diluted with water and extraction was carried out using ethyl acetate. The combined organic layers were washed with water, dried and concentrated under reduced pressure. The crude material was purified by silica gel column chromatography to afford the title compound (1.35 g, 74%).
Reaction SMILES: [C:1]([C:3]1[CH:4]=[N+:5]([O-])[C:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:11]=2[CH:12]=1)#[N:2].FC(F)(F)C(OC(=O)C(F)(F)F)=[O:17]>>[OH:17][CH:7]1[C:6]2[N:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:12][C:11]=2[CH2:10][CH2:9][CH2:8]1
Reactant: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Reactant: N#Cc1cc2c([n+]([O-])c1)CCCC2
Product: N#Cc1cnc2c(c1)CCCC2O
Temperature: 23 °C
Reaction time: 18 h
Yield: 87.2 %

Procedure:
To a solution of 3-cyano-5,6,7,8-tetrahydroquinoline 1-oxide (645 mg, 3.7 mmol) was added dropwise under ice cooling trifluoroacetic anhydride (6.22 g, 4.18 ml, 29.6 mmol). The light yellow solution was stirred at 23° C. for 18 h. The mixture was quenched with a solution of sodium hydroxide (1N) and stirred vigorously for 30 minutes, then extracted twice with dichloromethane. The combined organic layers were dried over sodium sulphate, filtered and evaporated. The residue was purified by silica gel flash chromatography with n-heptane/ethyl acetate to give the 8-hydroxy-5,6,7,8-tetrahydroquinoline-3-carbonitrile (562 mg, 87% yield) as a white solid. MS (ISP): m/z=175.1 [M+H]+.
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4]([CH2:13][CH2:14][OH:15])[C:5](=[O:12])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[C:16](Cl)(=[O:34])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]/[CH:24]=[CH:25]\[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33]>>[C:16]([O:1][CH2:2][CH2:3][N:4]([CH2:13][CH2:14][O:15][C:16](=[O:34])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]/[CH:24]=[CH:25]\[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])[C:5](=[O:12])[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1)(=[O:34])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]/[CH:24]=[CH:25]\[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)Cl
Reactant: O=C(c1ccccc1)N(CCO)CCO
Product: CCCCCCCC/C=C\CCCCCCCC(=O)OCCN(CCOC(=O)CCCCCCC/C=C\CCCCCCCC)C(=O)c1ccccc1

Procedure:
N,N-bis(oleoyloxyethyl)benzamide was prepared by the procedue of example 1 from 19.5 gms. (0.1 mole) of N,N-bis(2-hydroxyethyl)benzamide and 60 gms. (0.2 mole) of oleoyl chloride. The structure of the final product was characterized on the basis of IR and NMR spectral analyses as described in example 1.
Reaction SMILES: [C:1]1([O:7][C:8](=[O:34])[N:9]([C@:11]([C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[C:28]([Cl:33])[CH:27]=2)([CH2:22][CH2:23][CH2:24][OH:25])[CH2:12][N:13]([CH3:21])[C:14](=[O:20])[CH2:15][C:16]([F:19])([F:18])[F:17])[CH3:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.O>CS(C)=O>[C:1]1([O:7][C:8](=[O:34])[N:9]([C@:11]([C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[C:28]([Cl:33])[CH:27]=2)([CH2:22][CH2:23][CH:24]=[O:25])[CH2:12][N:13]([CH3:21])[C:14](=[O:20])[CH2:15][C:16]([F:19])([F:17])[F:18])[CH3:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CN(C[C@](CCCO)(c1ccc(Cl)c(Cl)c1)N(C)C(=O)Oc1ccccc1)C(=O)CC(F)(F)F
Solvent: O
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Product: CN(C[C@](CCC=O)(c1ccc(Cl)c(Cl)c1)N(C)C(=O)Oc1ccccc1)C(=O)CC(F)(F)F
Temperature: 25 °C
Reaction time: 4 h
Yield: 115.4 %

Procedure:
Under argon, phenyl[1-(3,3,3-trifluoro-N-methylpropanamido)-2-(S)-(3,4-dichlorophenyl)-5-hydroxy-pentan-2-yl]methylcarbamate (100 mg) was dissolved in anhydrous dimethyl sulfoxide (1.0 mL). At room temperature, triethylamine (0.16 mL) and pyridine sulfur trioxide complex (94 mg) were added thereto, and the mixture was stirred for 4 hours at room temperature. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was sequentially washed with water and saturated brine and dried over sodium sulfate anhydrate. The solvent was concentrated under reduced pressure, to thereby give the title compound (115 mg).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][CH2:9][C@H:10]2[CH2:15][CH2:14][CH2:13][CH2:12][N:11]2[CH2:16][CH:17]2[CH2:19][CH2:18]2)[C:5](=[O:20])[N:4]([CH2:21][C:22]([NH:24][CH2:25][C:26]2[CH:27]=[C:28]3[C:32](=[CH:33][CH:34]=2)[NH:31][CH:30]=[C:29]3[CH3:35])=[O:23])[C:3]=1[CH3:36]>[OH-].[Pd+2].[OH-]>[CH:17]1([CH2:16][N:11]2[CH2:12][CH2:13][CH2:14][CH2:15][C@@H:10]2[CH2:9][NH:8][C:6]2[C:5](=[O:20])[N:4]([CH2:21][C:22]([NH:24][CH2:25][C:26]3[CH:27]=[C:28]4[C:32](=[CH:33][CH:34]=3)[NH:31][CH:30]=[C:29]4[CH3:35])=[O:23])[C:3]([CH3:36])=[CH:2][N:7]=2)[CH2:19][CH2:18]1.[NH3:4]
Reactant: Cc1c[nH]c2ccc(CNC(=O)Cn3c(C)c(Cl)nc(NC[C@H]4CCCCN4CC4CC4)c3=O)cc12
Agent: [Pd+2]
Agent: [OH-]
Product: Cc1c[nH]c2ccc(CNC(=O)Cn3c(C)cnc(NC[C@H]4CCCCN4CC4CC4)c3=O)cc12
Product: N

Procedure:
The title compound was prepared by a similar method to preparation 44 from 2-[3-chloro-5-({[(2R)-1-(cyclopropylmethyl)piperidinyl]methyl}amino)-2-methyl-6-oxo-1(6H)-pyrazinyl]-N-[(3-methyl-1H-indol-5-yl)methyl]acetamide [see preparation 73] and palladium hydroxide. The crude product was purified by column chromatography on silica gel using dichloromethane:methanol:0.88 ammonia (90:10:1) as the eluant to afford the product as a white solid, (36%).
Reaction SMILES: [NH2:1][C:2]1[CH2:7][O:6][CH2:5][C@:4]2([C:20]3[C:15](=[N:16][CH:17]=[C:18]([OH:21])[CH:19]=3)[O:14][C:13]3[C:8]2=[CH:9][C:10]([C:22]2[C:23]([F:28])=[N:24][CH:25]=[CH:26][CH:27]=2)=[CH:11][CH:12]=3)[N:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:35](I)[C:36]([CH3:39])([CH3:38])[CH3:37]>CN(C=O)C.CC1OCCC1>[F:28][C:23]1[C:22]([C:10]2[CH:9]=[C:8]3[C@:4]4([N:3]=[C:2]([NH2:1])[CH2:7][O:6][CH2:5]4)[C:20]4[C:15](=[N:16][CH:17]=[C:18]([O:21][CH2:35][C:36]([CH3:39])([CH3:38])[CH3:37])[CH:19]=4)[O:14][C:13]3=[CH:12][CH:11]=2)=[CH:27][CH:26]=[CH:25][N:24]=1
Reactant: NC1=N[C@@]2(COC1)c1cc(-c3cccnc3F)ccc1Oc1ncc(O)cc12
Reactant: CC(C)(C)CI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC1CCCO1
Solvent: CN(C)C=O
Product: CC(C)(C)COc1cnc2c(c1)[C@]1(COCC(N)=N1)c1cc(-c3cccnc3F)ccc1O2
Yield: 15.9 %

Procedure:
A vial charged with a solution of (S)-3-bromo-7-iodo-2′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,3′-[1,4]oxazin]-5′-amine (0.880 g, 1.864 mmol), 2-fluoropyridin-3-ylboronic acid (0.276 g, 1.957 mmol), PdCl2(dppf)-CH2Cl2-adduct (0.038 g, 0.047 mmol), and potassium carbonate (1.031 g, 7.46 mmol). Dioxane (10 mL) and water (5 mL) were added, and the vial was flushed with argon and heated to 100° C. for 90 minutes. Pd2(dba)3 (0.171 g, 0.186 mmol), di-tert-butyl(2′,4′,6′-triisopropyl-3,4,5,6-tetramethylbiphenyl-2-yl)phosphine (0.224 g, 0.466 mmol), and potassium hydroxide (1.046 g, 18.64 mmol) were added to the reaction mixture. The vial was sealed and heated to 120° C. for an additional 3 hours. The reaction mixture was then neutralized to pH 7 with 1N HCl, and was diluted with 2-MeTHF. The organics were dried over MgSO4 and concentrated. Purification of the crude residue by column chromatography [0-100% (90:10:1 DCM/MeOH/NH4OH)/DCM] gave (S)-5′-amino-7-(2-fluoropyridin-3-yl)-2′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,3′-[1,4]oxazin]-3-ol (0.133 g, 0.352 mmol). Step 2: A solution of (S)-5′-amino-7-(2-fluoropyridin-3-yl)-2′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,3′-[1,4]oxazin]-3-ol (0.133 g, 0.352 mmol), potassium carbonate (0.194 g, 1.406 mmol), and neopentyl iodide (0.093 mL, 0.703 mmol) in 1.5 mL DMF was heated to 115° C. overnight. The reaction mixture was then diluted with 2-MeTHF and washed with water. The organics were dried over MgSO4 and concentrated. Purification of the crude residue by column chromatography [0-100% (9:1 EtOAc/MeOH)/DCM] gave (S)-7-(2-fluoropyridin-3-yl)-3-(neopentyloxy)-2′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,3′-[1,4]oxazin]-5′-amine (0.025 g, 0.056 mmol, 15.86% yield). MS m/z=449.20 [M+H]+. Calculated for C25H25FN4O3: 448.49.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](S(C)=O)[N:5]=[C:4]2[N:11]([C:16]3[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:17]=3[F:23])[C:12](=[O:15])[NH:13][CH2:14][C:3]=12.[N:24]1([CH:29]2[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)[CH2:28][CH2:27][CH2:26][CH2:25]1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[Cl:1][C:2]1[N:7]=[C:6]([N:32]2[CH2:33][CH2:34][CH:29]([N:24]3[CH2:28][CH2:27][CH2:26][CH2:25]3)[CH2:30][CH2:31]2)[N:5]=[C:4]2[N:11]([C:16]3[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:17]=3[F:23])[C:12](=[O:15])[NH:13][CH2:14][C:3]=12
Reactant: C1CCN(C2CCNCC2)C1
Reactant: CS(=O)c1nc(Cl)c2c(n1)N(c1c(F)cccc1F)C(=O)NC2
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: O=C1NCc2c(Cl)nc(N3CCC(N4CCCC4)CC3)nc2N1c1c(F)cccc1F
Yield: 80.5 %

Procedure:
To a solution of 5-chloro-1-(2,6-difluorophenyl)-7-(methylsulfinyl)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one (250 mg, 0.70 mmol) in DCM (10 mL) were added 4-(1-pyrrolidinyl)piperidine (323 mg, 2.1 mmol) and N,N-diisopropylethylamine (0.3 mL, 1.7 mmol). The resultant solution was stirred at room temperature over night. The result mixture was concentrated. CombiFlash chromatography (mobile phase DCM/DCM[90]+MeOH[7]+NH4OH[3]) provided the title compound as a white solid (253 mg, 81%). LC-MS m/z 449 (M+H)+
Reaction SMILES: Br.[Cl:2][C:3]1[C:4]2[N:5]([CH:9]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([S:18]([CH3:21])(=[O:20])=[O:19])=[CH:14][C:13]=3[O:22][CH3:23])[N:11]=2)[CH:6]=[CH:7][N:8]=1.CN(C)C=O>[Pd].C(N(CC)CC)C>[ClH:2].[ClH:2].[CH3:23][O:22][C:13]1[CH:14]=[C:15]([S:18]([CH3:21])(=[O:20])=[O:19])[CH:16]=[CH:17][C:12]=1[C:10]1[N:11]=[C:4]2[CH2:3][NH:8][CH2:7][CH2:6][N:5]2[CH:9]=1
Reactant: COc1cc(S(C)(=O)=O)ccc1-c1cn2ccnc(Cl)c2n1
Agent: [Pd]
Agent: Br
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: COc1cc(S(C)(=O)=O)ccc1-c1cn2c(n1)CNCC2
Product: Cl
Reaction time: 1.25 h

Procedure:
A suspension of 4.5 g. of 8-chloro-2-(2-methoxy-4-methylsulfonylphenyl)imidazo[1,2-a]pyrazine hydrobromide in 190 ml. of dimethylformamide was treated with 3.4 g. of triethylamine and 1 g. of 5% palladium-on-carbon. This mixture was hydrogenated at room temperature at 60 psi for about 75 minutes. The catalyst was removed by filtration and the solvent was removed in vacuo. During the course of solvent removal a precipitate occurred which was removed by filtration. The precipitate was triturated with chloroform and the residue was suspended in methanolic hydrogen chloride. After stirring for a period of time, the methanol was removed by evaporation and the resulting solid was collected with acetone by filtration affording 2.1 g. of the desired title product, M+ =307.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N:16]2[CH2:20][C@H:19]([CH2:21][NH:22][C:23](=O)[CH3:24])[O:18][C:17]2=[O:26])[CH:5]=[CH:6][C:7]=1[CH:8]1[CH2:13][CH2:12][S:11](=[O:15])(=[O:14])[NH:10][CH2:9]1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:36])=CC=1>O1CCOCC1>[F:1][C:2]1[CH:3]=[C:4]([N:16]2[CH2:20][C@H:19]([CH2:21][NH:22][C:23](=[S:36])[CH3:24])[O:18][C:17]2=[O:26])[CH:5]=[CH:6][C:7]=1[CH:8]1[CH2:13][CH2:12][S:11](=[O:15])(=[O:14])[NH:10][CH2:9]1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: CC(=O)NC[C@H]1CN(c2ccc(C3CCS(=O)(=O)NC3)c(F)c2)C(=O)O1
Solvent: C1COCCO1
Product: CC(=S)NC[C@H]1CN(c2ccc(C3CCS(=O)(=O)NC3)c(F)c2)C(=O)O1
Yield: 91.7 %

Procedure:
N-[[(5S)-3-[3-Fluoro-4-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide (180 mg, 0.47 mmol), Lawesson's Reagent (310 mg, 0.77 mmol) and dioxane (10 ml) are heated under reflux for 1 hr. After cooling, the solvent is evaporated and the residue chromatographed over silica gel (40 g) eluting with 2-4% methanol-chloroform gives the title compound as a foam (173 mg, 92%). HRMS(FAB): calcd for m+H=402.0957; Found: 402.0954.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]2[O:9][C:10]3[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[CH:12][C:11]=3[C:7]=2[C:6]([CH:19]=[O:20])=[CH:5][CH:4]=1.[Mn]([O-])(=O)(=O)=[O:22].[K+]>CC(C)=O.O.CC(C)=O>[CH3:1][O:2][C:3]1[C:8]2[O:9][C:10]3[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[CH:12][C:11]=3[C:7]=2[C:6]([C:19]([OH:22])=[O:20])=[CH:5][CH:4]=1
Reactant: O=[Mn](=O)(=O)[O-]
Reactant: COc1ccc(C=O)c2c1oc1ccc([N+](=O)[O-])cc12
Agent: [K+]
Solvent: CC(C)=O
Solvent: O
Product: COc1ccc(C(=O)O)c2c1oc1ccc([N+](=O)[O-])cc12
Temperature: 65 °C
Yield: 61.4 %

Procedure:
Intermediate 28 (1.1 gm, 0.0034 mol) in acetone (5 ml) was heated to 60-70° C. for 10 min. To the above suspension was added dropwise a hot solution of potassium permanganate (1.07 gm, 0.0068 mol) in water:acetone (1: 3) (15 ml) for 10 min. The reaction was heated to 60-70° C. for 10 min., cooled to room temperature and filtered. The residue washed with acetone and the filterate was extracted with 10% sodium hydroxide solution. Acidification, followed by filteration and washing of the precipitate yielded 4-methoxy-8-nitro-dibenzo[b,d]furan-1-carboxylic acid (0.6 gm) as white solid, mp: 178° C. (dec.)
Reaction SMILES: [CH2:1]([NH:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[C:15]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[C:16]3[CH2:21][NH:20][CH2:19][C:17]=3[N:18]=2)=[CH:9][CH:8]=1)=[O:5])[CH3:2].Cl[C:29]([O:31][CH2:32][CH3:33])=[O:30]>>[CH2:1]([NH:3][C:4](=[O:5])[NH:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[C:15]([N:22]3[CH2:23][CH2:24][O:25][CH2:26][CH2:27]3)[C:16]3[CH2:21][N:20]([C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH2:19][C:17]=3[N:18]=2)=[CH:9][CH:8]=1)[CH3:2]
Reactant: CCNC(=O)Nc1ccc(-c2nc3c(c(N4CCOCC4)n2)CNC3)cc1
Reactant: CCOC(=O)Cl
Product: CCNC(=O)Nc1ccc(-c2nc3c(c(N4CCOCC4)n2)CN(C(=O)OCC)C3)cc1

Procedure:
Method as described for example 34 using 1-ethyl-3-(4-(4-morpholino-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea (example 14) and ethyl chloroformate as starting materials.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C:13]([CH3:14])=[CH:12][CH2:11][CH2:10][CH:9]1[CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:20]([BH3-])#N.[Na+].C(O)(C(F)(F)F)=O.CCOC(C)=O>C(Cl)Cl>[C:6]([N:8]1[C@@H:9]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[CH2:10][CH2:11][CH2:12][C@@H:13]1[CH3:14])([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7]
Reactant: CCCCCC1CCC=C(C)N1C(=O)OC(C)(C)C
Reactant: [BH3-]C#N
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CCCCCC[C@H]1CCC[C@H](C)N1C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 53.7 %

Procedure:
To a stirred solution of 1-(tert-Butoxycarbonyl)-6-methyl-2-n-pentyl-1,2,3,4-tetrahydropyridine (1.0 g, 3.55 mmol) in 240 mL of CH2Cl2 was added sodium cyanoborohydride (1.34 g, 21.3 mmol). After being stirred 15 minutes at room temperature, the heterogeneous solution was cooled to −42° C. and TFA (3.5 mL, 35.53 mmol) was added slowly dropwise. After being stirred for 4 h at −42° C., the cold bath was removed, and the reaction mixture was immediately quenched with 200 mL of a saturated aqueous NaHCO3/THF mixture (50:50). The aqueous phase was extracted with CH2Cl2 (2×70 mL) and the combined organic extracts were washed with water and brine. The organic phase was dried with K2CO3, filtered through Celite, and evaporated to give crude product. Column chromatography using 5% EtOAc in hexanes gave 0.54 g (54%) of the product which was homogeneous by TLC analysis. 1H NMR (300 MHz) δ 3.99-3.82 (m, 1H), 3.79-3.74 (m, 1H), 1.91-1.15 (m, 28H), 0.92-0.83 (t, 3H); 13C NMR (75 Mhz) 155.6 (s), 78.6 (s), 51.6 (s), 46.9 (s) 34.34 (s), 31.9 (s), 29.3 (s), 28.5 (s), 27.1 (s), 26.9 (s), 23.1 (s), 22.6 (s), 20.8 (s), 14.0 (s), 13.7 (s) ppm.
Reaction SMILES: [CH3:1][C:2](=[CH2:6])[C:3]([OH:5])=[O:4].C1(O)C=CC(O)=CC=1.[S:15]1[C:19]2[CH:20]=[C:21]([NH2:24])[CH:22]=[CH:23][C:18]=2[N:17]=[CH:16]1.CO>C1(C)C=CC=CC=1.C(Cl)(Cl)Cl>[S:15]1[C:19]2[CH:20]=[C:21]([NH:24][CH2:6][CH:2]([CH3:1])[C:3]([OH:5])=[O:4])[CH:22]=[CH:23][C:18]=2[N:17]=[CH:16]1
Reactant: C=C(C)C(=O)O
Reactant: Nc1ccc2ncsc2c1
Agent: Oc1ccc(O)cc1
Solvent: Cc1ccccc1
Solvent: CO
Solvent: ClC(Cl)Cl
Product: CC(CNc1ccc2ncsc2c1)C(=O)O
Temperature: 100 °C
Yield: 27.4 %

Procedure:
2-Methyl-acrylic acid (0.63 g, 0.00732 mol) and Benzene-1,4-diol (0.029 g, 0.000266 mol) were added to a stirred solution of Benzothiazol-6-ylamine (1 g, 0.00665 mol) in toluene (6 mL) under nitrogen atmosphere. The resulting reaction mass was heated at 70° C. for 72 hours and further at 100° C. for 48 hours. The reaction was monitored by TLC (5% methanol in chloroform). The reaction mixture was cooled to room temperature and partitioned between water and ethyl acetate. The organic layer was washed with brine solution, dried over Na2SO4 and concentrated to afford the crude product. Purification by column chromatography on silica gel (0.75% methanol in chloroform) afforded 0.43 g of the product (26.87% yield).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[C:10](=[O:15])[CH2:11][CH2:12][C:13]=1[CH3:14].N1C=CC=CC=1.[C:22]1([CH3:32])[CH:27]=[CH:26][C:25]([S:28](Cl)(=[O:30])=[O:29])=[CH:24][CH:23]=1>>[C:22]1([CH3:32])[CH:27]=[CH:26][C:25]([S:28]([NH:1][C:2]2[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=2[C:9]2[C:10](=[O:15])[CH2:11][CH2:12][C:13]=2[CH3:14])(=[O:30])=[O:29])=[CH:24][CH:23]=1
Reactant: CC1=C(c2cc(F)ccc2N)C(=O)CC1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: c1ccncc1
Product: CC1=C(c2cc(F)ccc2NS(=O)(=O)c2ccc(C)cc2)C(=O)CC1

Procedure:
0.700 g (3.14 mmol) of 2-(2-amino-5-fluorophenyl)-3-methyl-2-cyclopenten-1-one, 0.298 g (3.76 mmol) of pyridine, 0.598 g (3.76 mmol) of p-toluenesulfonyl chloride, and 3 mL of M.C were loaded to a 20 mL vial, and then reacted for 12 hours. The work-up was the same as in Example 7 (1.000 g, 85%).
Reaction SMILES: [OH-].[K+].[Cl:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]#[C:11][Si](C)(C)C.C(OCC)(=O)C.Cl>CO.CCCCCC>[Cl:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]#[CH:11]
Reactant: C[Si](C)(C)C#Cc1ccccc1Cl
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: C#Cc1ccccc1Cl
Temperature: 0 °C
Yield: 65.6 %

Procedure:
Potassium hydroxide (77.5 g, 1.38 mol) was added in 4 portions to a stirred solution of (2-chlorophenylethynyl)-trimethylsilane (95.0 g, 0.46 mol) in methanol (250 ml) at 0° C. The mixture was stirred at 0° C. until the reaction was complete (by tlc 1:1 ethyl acetate:hexane). The mixture was neutralised by the addition of 10% hydrochloric acid and the product was extracted into dichloromethane (2×150 ml). The combined extracts were dried (MgSO4) and evaporated in vacuo. The residual oil was purified by short path distillation (Kugelrohr) to give 1-chloro-2-ethynylbenzene (41.23 g) as a clear oil. B.pt. 38° C./10 mBar. 250 MHz 1H-NMR (CDCl3) δ (ppm): 3.25 (s, 1H)(CH), 7.1-7.5 (m, 4H) (ArH); GC purity 89%, GC retention time 2.67 min.