Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[CH:5]=[CH:4][C:3]([C:6]([OH:8])=O)=[CH:2]1.C(C1C=C(C(C)C)C=C(C(C)C)C=1S(Cl)(=O)=O)(C)C.[Si]([O:35][C@@H:36]1[C@H:40]([O:41][Si](C(C)(C)C)(C)C)[C@@H:39]([CH3:49])[O:38][C@H:37]1[N:50]1[CH:57]=[C:56]([F:58])[C:54]([NH2:55])=[N:53][C:51]1=[O:52])(C(C)(C)C)(C)C>N1C=CC=CC=1.CN(C)C1C=CN=CC=1>[F:58][C:56]1[C:54]([NH:55][C:6]([C:3]2[CH:4]=[CH:5][O:1][CH:2]=2)=[O:8])=[N:53][C:51](=[O:52])[N:50]([CH:57]=1)[C@@H:37]1[O:38][C@H:39]([CH3:49])[C@@H:40]([OH:41])[C@H:36]1[OH:35]
Reactant: O=C(O)c1ccoc1
Reactant: C[C@H]1O[C@@H](n2cc(F)c(N)nc2=O)[C@H](O[Si](C)(C)C(C)(C)C)[C@@H]1O[Si](C)(C)C(C)(C)C
Agent: CC(C)c1cc(C(C)C)c(S(=O)(=O)Cl)c(C(C)C)c1
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Product: C[C@H]1O[C@@H](n2cc(F)c(NC(=O)c3ccoc3)nc2=O)[C@H](O)[C@@H]1O
Reaction time: 1 h
Yield: 76.8 %

Procedure:
3-Furoic acid (0.355 g) and 2,4,6-triisopropyl benzene-sulfonyl chloride (0.96 g) were dissolved in dry pyridine (5 ml). The mixture was stirred for 1 hour. To the mixture were added 2',3'-bis-O-(tert-butyldimethylsilyl)-5'-deoxy-5-fluorocytidine (1.0 g) obtained in Reference example (a) and 4-dimethylaminopyridine (0.80 g). After stirring of the mixture for 12 hours at room temperature. pyridine was evaporated under reduced pressure. The residue was then treated as in Example 48 to give 0.55 g of 5'-deoxy-5-fluoro-N4 -(3-furoyl)cytidine, mp 173°~174° C. (ethanol); MS 340 (MH+).
Reaction SMILES: Cl.Br[C:3]1[C:4]2[N:5]([CH:16]=[CH:17][N:18]=2)[N:6]=[C:7]([Cl:15])[C:8]=1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[CH3:19][CH2:20][O:21][C:22]1[CH:23]=[CH:24][C:25]([NH2:28])=[CH:26][CH:27]=1.CC([O-])(C)C.[K+]>>[Cl:15][C:7]1[C:8]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[C:3]([NH:28][C:25]2[CH:24]=[CH:23][C:22]([O:21][CH2:20][CH3:19])=[CH:27][CH:26]=2)[C:4]2[N:5]([CH:16]=[CH:17][N:18]=2)[N:6]=1
Reactant: Clc1nn2ccnc2c(Br)c1-c1ccccc1
Reactant: CCOc1ccc(N)cc1
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Product: CCOc1ccc(Nc2c(-c3ccccc3)c(Cl)nn3ccnc23)cc1
Temperature: 25 °C
Reaction time: 0.02 h

Procedure:
To a solution of 8-bromo-6-chloro-7-phenylimidazo[1,2-b]pyridazine HCl salt (0.0431 g, 0.125 mmol) from 1c and 4-ethoxyaniline (0.31 M in THF, 0.40 mL) under nitrogen at 0° C. was added KOtBu (1 N in THF, 0.32 mL, 0.32 mmol). After 1 min, the cold bath was removed, and the reaction mixture was stirred to room temperature for 1 h. After concentrating in vacuo, the residue was taken up in CH2Cl2 and water, and the layers were separated. The aqueous layer was extracted with CH2Cl2 (2×). The organic layers were combined, dried over Na2SO4, filtered, and concentrated in vacuo. Trituration with hexanes provided 6-chloro-N-(4-ethoxyphenyl)-7-phenylimidazo[1,2-b]pyridazin-8-amine (0.0334 g).
Reaction SMILES: [Na+].[Na+].[Cl:3][C:4]([Cl:13])([P:9](=[O:12])([O-:11])[O-:10])[P:5](=[O:8])([OH:7])[OH:6].C(N(CCCC)CCCC)CCC>>[Cl:13][C:4]([Cl:3])([P:5](=[O:6])([OH:8])[OH:7])[P:9](=[O:10])([OH:11])[OH:12]
Reactant: O=P([O-])([O-])C(Cl)(Cl)P(=O)(O)O
Agent: [Na+]
Solvent: CCCCN(CCCC)CCCC
Product: O=P(O)(O)C(Cl)(Cl)P(=O)(O)O

Procedure:
An aqueous solution of dichloromethylenediphosphonic acid disodium salt (1.0 g, 3.46 mmol) was loaded on a column of DOWEX 50WX8-100 ion-exchange resin and eluted with water. Tributylamine (1.65 mL, 6.92 mmol) was added and the mixture was shaken vigorously. The resulting solution was concentrated to dryness and coevaporated with anhydrous DMF three times. The residue was dried under vacuum overnight.
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[C:8]([CH:15](C(OCC)=O)[C:16]([O:18]CC)=[O:17])[CH:9]=[CH:10][C:11]=2[N+:12]([O-:14])=[O:13])[CH2:3][CH2:2]1.[OH-].[Na+]>C(O)C>[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[C:8]([CH2:15][C:16]([OH:18])=[O:17])[CH:9]=[CH:10][C:11]=2[N+:12]([O-:14])=[O:13])[CH2:2][CH2:3]1
Reactant: CCOC(=O)C(C(=O)OCC)c1ccc([N+](=O)[O-])c(OCC2CC2)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=C(O)Cc1ccc([N+](=O)[O-])c(OCC2CC2)c1
Temperature: 0 °C
Yield: 90.9 %

Procedure:
Compound diethyl 2-(3-(cyclopropylmethoxy)-4-nitrophenyl)malonate (10 g) was dissolved in 100 mL ethanol and cooled to 0° C., NaOH solution (4 eq) was added slowly to the reaction mixture for about 15 min. The reaction mixture was heated gently up to 60° C. for 5 h. Progress of the reaction was monitored by TLC analysis. After complete conversion of starting material solvent was evaporated under reduced pressure, residue dissolved in H2O, acidified with 6N HCl to pH-2. Filtered the solid material washed with water, dried under reduced pressure to give 2-(3-(cyclopropylmethoxy)-4-nitrophenyl)acetic acid (6.5 g) as a yellow solid. 1H-NMR (CDCl3, 200 MHz): 0.36 (m, 2H), 0.58 (m, 2H), 1.28 (m, 1H), 3.71 (s, 2H), 4.01 (d, 2H), 7.02 (d, 1H), 7.23 (s, 1H), 7.81 (d, 1H).
Reaction SMILES: [CH2:1]([O:5][C:6]1[C:11]([CH3:12])=[CH:10][C:9]([CH2:13][CH:14]=[CH2:15])=[CH:8][C:7]=1[CH3:16])[CH:2]1[O:4][CH2:3]1.C([O-])(=[O:19])C.[Na+].C(OO)(=O)C>C(Cl)(Cl)Cl>[CH2:1]([O:5][C:6]1[C:7]([CH3:16])=[CH:8][C:9]([CH2:13][CH:14]2[O:19][CH2:15]2)=[CH:10][C:11]=1[CH3:12])[CH:2]1[O:4][CH2:3]1
Reactant: CC(=O)[O-]
Reactant: C=CCc1cc(C)c(OCC2CO2)c(C)c1
Agent: CC(=O)OO
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: Cc1cc(CC2CO2)cc(C)c1OCC1CO1
Reaction time: 4 h
Yield: 863.5 %

Procedure:
A 350 ml sulfurating flask equipped with thermometer, stirrer, cooler and drip funnel is charged with 46.30 g (0.21 mole) of 4-allyl-2,6-dimethylphenyl glycidyl ether, 1.93 g of sodium acetate and 160 ml of chloroform, and the batch is heated to 35°-40° C. At this temperature, 52.3 g (0.28 mole) of 40% peracetic acid are then added dropwise over about 1 hour. The reaction mixture is then held at this temperature for a further 4 hours until the educt is no longer discernible in the gas chromatograph. When the reaction is complete, the reaction mixture is diluted in chloroform and the resultant solution is washed with 3% NaOH until neutral, made peroxide-free with sodium sulfite, dried over sodium sulfate and filtered. The filtrate is concentrated by rotary evaporation, affording 47.6 g of 4-(2,3-epoxypropyl)-2,6-dimethylphenyl glycidyl ether in the form of a low viscous oil; epoxide content 8.1 equivalents/kg (95.13% of theory).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH:7]([CH2:14][CH2:15][CH2:16][CH2:17][C:18]1[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=1)[CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10].C(N(CC)CC)C.[Cl:31][C:32]1[CH:37]=[CH:36][C:35]([S:38](Cl)(=[O:40])=[O:39])=[CH:34][CH:33]=1>C(Cl)Cl>[Cl:31][C:32]1[CH:37]=[CH:36][C:35]([S:38]([NH:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH:7]([CH2:14][CH2:15][CH2:16][CH2:17][C:18]2[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=2)[CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])(=[O:40])=[O:39])=[CH:34][CH:33]=1
Reactant: O=S(=O)(Cl)c1ccc(Cl)cc1
Reactant: CCOC(=O)CC(CCCCCN)CCCCc1cccnc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCOC(=O)CC(CCCCCNS(=O)(=O)c1ccc(Cl)cc1)CCCCc1cccnc1

Procedure:
To a solution of 1.0 g of ethyl 8-amino-3-[4-(3-pyridyl)-butyl]-octanoate in 100 ml of methylene chloride is added 3 g of triethylamine followed by the dropwise addition of a solution of 1.5 g of p-chlorophenylsulfonyl chloride in 15 ml of methylene chloride. The reaction mixture is concentrated then directly purified by chromatography on silica gel using 25% ethyl acetate in methylene chloride as eluent to yield ethyl 8-(p-chlorophenylsulfonamido)-3-[4-(3-pyridyl)-butyl]-octanoate.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[N+:11]([O-:13])=[O:12])[N:7]([CH2:14][CH2:15][CH2:16][CH3:17])[C:6](=[O:18])[C:5]2([CH3:20])[CH3:19].[CH:21]([O:24][C:25]1[CH:30]=[CH:29][C:28]([CH2:31][CH2:32][C:33](Cl)=[O:34])=[CH:27][CH:26]=1)([CH3:23])[CH3:22]>>[CH2:14]([N:7]1[C:8]2[C:4](=[CH:3][C:2]([NH:1][C:33](=[O:34])[CH2:32][CH2:31][C:28]3[CH:29]=[CH:30][C:25]([O:24][CH:21]([CH3:22])[CH3:23])=[CH:26][CH:27]=3)=[C:10]([N+:11]([O-:13])=[O:12])[CH:9]=2)[C:5]([CH3:19])([CH3:20])[C:6]1=[O:18])[CH2:15][CH2:16][CH3:17]
Reactant: CCCCN1C(=O)C(C)(C)c2cc(N)c([N+](=O)[O-])cc21
Reactant: CC(C)Oc1ccc(CCC(=O)Cl)cc1
Product: CCCCN1C(=O)C(C)(C)c2cc(NC(=O)CCc3ccc(OC(C)C)cc3)c([N+](=O)[O-])cc21

Procedure:
N-(1-Butyl-3,3-dimethyl-6-nitro-2-oxo-2,3-dihydro-1H-indol-5-yl)-3-(4-isopropoxy-phenyl)-propionamide is prepared from A4 (500 mg) and 3-(4-isopropoxy-phenyl)-propionyl chloride (1.01 g; 5.5 mmol) as described in Example 1a. The crude material is purified by flash chromatography eluting with light petroleum/EtOAc (6:1) to give the compound (791 mg).
Reaction SMILES: [NH2:1][CH:2]([C:10]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:13]=[CH:12][C:11]=1[O:20][CH3:21])[CH2:3][CH2:4][CH2:5][C:6]([O:8]C)=O.[O:22]([C:29]1[CH:30]=[C:31]([CH:34]=[CH:35][CH:36]=1)[CH:32]=O)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>>[CH3:21][O:20][C:11]1[CH:12]=[CH:13][C:14]2[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:10]=1[CH:2]1[N:1]([CH2:32][C:31]2[CH:34]=[CH:35][CH:36]=[C:29]([O:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH:30]=2)[C:6](=[O:8])[CH2:5][CH2:4][CH2:3]1
Reactant: COC(=O)CCCC(N)c1c(OC)ccc2ccccc12
Reactant: O=Cc1cccc(Oc2ccccc2)c1
Product: COc1ccc2ccccc2c1C1CCCC(=O)N1Cc1cccc(Oc2ccccc2)c1

Procedure:
Prepared according to general procedure 1 (GP1) using methyl 5-amino-5-(2-methoxynaphthalen-1-yl)pentanoate and commercially available 3-phenoxybenzaldehyde. Subsequent purification by preparative HPLC afforded the target compound. LC-MS (conditions A): tR=0.99 min.; [M+H]+: 438.14 g/mol.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10](=O)[C:11](OCC(C)C)=[O:12])=[CH:2]1.[BH4-].[Na+]>C(O)(C)C.O>[OH:12][CH2:11][CH2:10][C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[NH:1][CH:2]=1
Reactant: CC(C)COC(=O)C(=O)c1c[nH]c2ccccc12
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CC(C)O
Product: OCCc1c[nH]c2ccccc12
Reaction time: 5 h

Procedure:
A stirred suspension of isobutyl 3-indolylglyoxylate (48.5 g.) and sodium borohydride (22.7 g.) in isopropanol (500 ml.) was slowly heated to reflux and held for 5 hours. The cooled mixture was diluted with water (2 l.) and extracted with dichloromethane. The extract was washed with water, dried over magnesium sulphate and concentrated under reduced pressure to an oil which crystallised on cooling. Recrystallisation from toluene (100 ml.) gave 3-(2-hydroxyethyl)indole as a cream-coloured crystalline powder, mp. 55°-56°. Yield 23.3 g. (72.3%).
Reaction SMILES: [CH3:1][C:2]1[CH:9]=[CH:8][C:7]([N:10]2[N:14]=[CH:13][CH:12]=[N:11]2)=[CH:6][C:3]=1[CH:4]=[O:5].[BH4-].[Na+]>CO>[CH3:1][C:2]1[CH:9]=[CH:8][C:7]([N:10]2[N:14]=[CH:13][CH:12]=[N:11]2)=[CH:6][C:3]=1[CH2:4][OH:5]
Reactant: Cc1ccc(-n2nccn2)cc1C=O
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: Cc1ccc(-n2nccn2)cc1CO
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 70.5 %

Procedure:
To a stirred solution of 2-methyl-5-(2H-1,2,3-triazol-2-yl)benzaldehyde (140 mg, 0.75 mmol) in methanol (10 mL), NaBH4 (42 mg, 1.1 mmol) was added at 10° C. and stirred for 10 min. Then the mixture was allowed to warm to rt and stirred for 1 h. The mixture was quenched with saturated aqueous NH4Cl solution (0.3 mL) and filtered over hyflow. The filtrate was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified flash column chromatography (eluent: 30% ethyl acetate in hexane) to yield the title compound (100 mg, 71%). [TLC Rf=0.18 (ethyl acetate/hexane 30:70)].
Reaction SMILES: C([NH:3][C:4]1[NH:8][N:7]=[C:6]([S:9]([NH:12][C:13]2[C:18]([Cl:19])=[CH:17][CH:16]=[C:15]([CH3:20])[C:14]=2[Cl:21])(=[O:11])=[O:10])[N:5]=1)=O.Cl>[OH-].[Na+]>[NH2:3][C:4]1[NH:8][N:7]=[C:6]([S:9]([NH:12][C:13]2[C:18]([Cl:19])=[CH:17][CH:16]=[C:15]([CH3:20])[C:14]=2[Cl:21])(=[O:11])=[O:10])[N:5]=1
Reactant: Cc1ccc(Cl)c(NS(=O)(=O)c2n[nH]c(NC=O)n2)c1Cl
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: Cc1ccc(Cl)c(NS(=O)(=O)c2n[nH]c(N)n2)c1Cl

Procedure:
A mixture of 3.5 g (10 mmol) of 5-formylamino-N-(2,6-dichloro-3-methylphenyl)-1,2,4-triazole-3-sulfonamide and 50 ml of 1 percent aqueous sodium hydroxide was heated to reflux for 4 hours and was then cooled and acidified with dilute aqueous hydrochloric acid. The solids that formed were collected by filtration and dried to obtain 2.77 g (86 percent of theory) of the title compound, m.p. 243°-44° C. The proton and carbon nmr spectra were consistent with the assigned structure.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:14]=[CH:15][C:16]=1[O:17][CH3:18])[C:6]([CH2:8][C:9]([O:11]CC)=O)=O.[CH2:19]([NH:26][NH2:27])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C(O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:6]2[NH:27][N:26]([CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:9](=[O:11])[CH2:8]2)[CH:14]=[CH:15][C:16]=1[O:17][CH3:18]
Reactant: CCOC(=O)CC(=O)c1ccc(OC)c(OC)c1
Reactant: NNCc1ccccc1
Solvent: CCO
Product: COc1ccc(C2CC(=O)N(Cc3ccccc3)N2)cc1OC
Temperature: 25 °C
Reaction time: 12 h
Yield: 53.4 %

Procedure:
6.6 g of ethyl 3,4-dimethoxybenzoylacetate were suspended in ethanol, and 3.5 g of benzylhydrazine were added dropwise with ice cooling over the course of 1.5 hours. The reaction mixture was stirred at room temperature for 12 hours. Then the precipitated product was filtered out and washed first with ethanol and then with tert-butyl methyl ether. 4.36 g of 5-(3,4-dimethoxyphenyl)-2-benzylpyrazolin-3-one were obtained. Melting point: 164°-166° C.
Reaction SMILES: [C:1]12([C:11](Cl)=[O:12])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[NH2:14][C:15]1[CH:16]=[N:17][C:18]2[C:23]([CH:24]=1)=[CH:22][CH:21]=[CH:20][CH:19]=2.N1C=CC=CC=1>O>[N:17]1[C:18]2[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:24]=[C:15]([NH:14][C:11]([C:1]23[CH2:10][CH:5]4[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]4)[CH2:2]2)[CH2:8]3)=[O:12])[CH:16]=1
Reactant: O=C(Cl)C12CC3CC(CC(C3)C1)C2
Reactant: Nc1cnc2ccccc2c1
Solvent: O
Solvent: c1ccncc1
Product: O=C(Nc1cnc2ccccc2c1)C12CC3CC(CC(C3)C1)C2
Yield: 28.3 %

Procedure:
Prepared from 1-adamantanecarbonyl chloride (0.75 g, 3.8 mmol), 3-aminoquinoline (0.60 g, 4.2 mmol), pyridine (10 mL), and water (100 mL) yielding 0.33 g (29%) of (86):
Reaction SMILES: [OH-].[Na+].C[O:4][C:5](=[O:50])[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([O:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[C:7]=1[O:31][CH2:32][CH2:33][CH2:34][O:35][C:36]1[CH:41]=[CH:40][C:39]([O:42][CH2:43][C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)=[CH:38][CH:37]=1>>[CH2:13]([O:12][C:8]1[C:7]([O:31][CH2:32][CH2:33][CH2:34][O:35][C:36]2[CH:41]=[CH:40][C:39]([O:42][CH2:43][C:44]3[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=3)=[CH:38][CH:37]=2)=[C:6]([CH:11]=[CH:10][CH:9]=1)[C:5]([OH:50])=[O:4])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30]
Reactant: CCCCCCCCCCCCCCCCCCOc1cccc(C(=O)OC)c1OCCCOc1ccc(OCc2ccccc2)cc1
Agent: [Na+]
Agent: [OH-]
Product: CCCCCCCCCCCCCCCCCCOc1cccc(C(=O)O)c1OCCCOc1ccc(OCc2ccccc2)cc1
Yield: 76 %

Procedure:
Sodium hydroxide hydrolysis of 3-(octadecyloxy)-2-[3-[4-(phenylmethoxy)phenoxy]propoxy]benzoic acid methyl ester gave 3-(octadecyloxy)-2-[3-[4-(phenylmethoxy)phenoxy]propoxy]benzoic acid (76% yield, mp 75°-76°).
Reaction SMILES: [CH3:1][Si:2]([CH3:12])([CH3:11])[C:3]#[C:4][CH2:5][C:6]1([CH2:9][OH:10])[CH2:8][CH2:7]1.[CH3:13][S:14](Cl)(=[O:16])=[O:15]>>[CH3:12][Si:2]([CH3:1])([CH3:11])[C:3]#[C:4][CH2:5][C:6]1([CH2:9][O:10][S:14]([CH3:13])(=[O:16])=[O:15])[CH2:8][CH2:7]1
Reactant: CS(=O)(=O)Cl
Reactant: C[Si](C)(C)C#CCC1(CO)CC1
Product: C[Si](C)(C)C#CCC1(COS(C)(=O)=O)CC1

Procedure:
In analogy to the procedure described in example 1G], [1-(3-trimethylsilanyl-prop-2-ynyl)-cyclopropyl]-methanol and methanesulfonyl chloride gave the title compound as yellow oil.
Reaction SMILES: [CH3:1][O:2][CH:3]([O:15][CH3:16])[CH:4]([S:9][CH2:10][CH2:11][C:12](=[O:14])[CH3:13])OC(=O)C.C([O-])([O-])=[O:18].[K+].[K+]>CO>[CH3:1][O:2][CH:3]([O:15][CH3:16])[CH2:4][S:9][CH2:10][CH:11]([OH:18])[C:12](=[O:14])[CH3:13]
Reactant: COC(OC)C(OC(C)=O)SCCC(C)=O
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: COC(CSCC(O)C(C)=O)OC
Reaction time: 0.17 h

Procedure:
To a solution of 200 mg. (0.8 mmol) of 2-acetoxy-3-oxobutylmercaptoacetaldehyde dimethylacetal in 2 ml. of methanol was added 110 mg. (0.8 mmol) of K2CO3. The reaction mixture was stirred 10 minutes, filtered, diluted with water and extracted with CHCl3. The CHCl3 extract was dried over Na2SO4, filtered and evaporated to 123 mg. (75%) of keto alcohol product: 1H-NMR (CDCl3) delta 2.20 (s, 3), 2.85 (m, 4), 3.32 (s, 6), 4.32 (m, 1), 4.45 (t, 1).
Reaction SMILES: C(=O)([S:3][CH:4]([CH2:14][N:15]1[C:23]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[C:22]2[C:17]([N:18]([CH3:33])[C:19](=[O:32])[N:20]([CH3:31])[C:21]2=[O:30])=[CH:16]1)[CH2:5][O:6][Si](C(C)(C)C)(C)C)C.[BH4-].[Na+].C(O)(C(F)(F)F)=O>CCO.O.C(Cl)Cl>[OH:6][CH2:5][CH:4]([SH:3])[CH2:14][N:15]1[C:23]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[C:22]2[C:17]([N:18]([CH3:33])[C:19](=[O:32])[N:20]([CH3:31])[C:21]2=[O:30])=[CH:16]1
Reactant: CC(=O)SC(CO[Si](C)(C)C(C)(C)C)Cn1cc2c(c1-c1ccccc1)c(=O)n(C)c(=O)n2C
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Cn1c(=O)c2c(-c3ccccc3)n(CC(S)CO)cc2n(C)c1=O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a stirred solution of S-(1-((tert-butyldimethylsilyl)oxy)-3-(1,3-dimethyl-2,4-dioxo-5-phenyl-3,4-dihydro-1H-pyrrolo[3,4-d]pyrimidin-6(2H)-yl)propan-2-yl) ethanethioate (step 4) (1.62 g, 3.23 mmol) in EtOH (25 ml) was added sodium borohydride (0.61 g, 16.14 mmol) at 0° C. and the solution stirred overnight at RT. The reaction mixture was added slowly to TFA in water (20 ml, 50%). The resulting solid was removed by filtration and the filtrate was concentrated in vacuo to remove EtOH. The resulting mixture was diluted with water and extracted with DCM (×3). The combined organic extracts were passed through a hydrophobic frit and concentrated under reduced pressure to afford an oil. The oil was dissolved in a minimal volume of DCM and purified via ISCO column chromatography, 12 g, liquid load, 0-90% EtOAc in iso-hexane to afford the title compound;
Reaction SMILES: [C:1](#[N:10])[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.[OH-:11].[Na+]>CO>[C:6]([C:5]1[CH:8]=[CH:9][C:2]([C:1]([NH2:10])=[O:11])=[CH:3][CH:4]=1)#[N:7]
Reactant: [OH-]
Reactant: N#Cc1ccc(C#N)cc1
Agent: [Na+]
Solvent: CO
Product: N#Cc1ccc(C(N)=O)cc1
Yield: 62.3 %

Procedure:
Terephthalonitrile (12.8 g, 0.1 mol) and methanol (170.1 g) were mixed, and the resultant mixture was heated to 64° C. with stirring. To the mixture, a 20% aqueous solution of sodium hydroxide (12 g) was added over six hours. Liquid chromatographic analysis revealed the reaction mixture contained 9.1 g of p-cyanobenzamide (yield 62%).
Reaction SMILES: [C:1]([NH:5][C:6]([C:8]1[N:9]([C:14](=[O:17])[CH2:15][CH3:16])[CH2:10][CH2:11][NH:12][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])O.[Na+].[C:23](Cl)(=[O:25])[CH3:24].O>C(OCCCC)(=O)C.C(#N)C.C(OCCCC)(=O)C>[C:1]([NH:5][C:6]([C:8]1[N:9]([C:14](=[O:17])[CH2:15][CH3:16])[CH2:10][CH2:11][N:12]([C:23](=[O:25])[CH3:24])[CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CCC(=O)N1CCNC=C1C(=O)NC(C)(C)C
Reactant: CC(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC#N
Solvent: O
Solvent: CCCCOC(C)=O
Product: CCC(=O)N1CCN(C(C)=O)C=C1C(=O)NC(C)(C)C
Temperature: 50 °C
Reaction time: 0.67 h
Yield: 92.7 %

Procedure:
168.7 g (0.705 mol) of 1-propionyl-1,4,5,6-tetrahydropyrazine-2-carboxylic acid tert-butylamide was placed in 1.92 l of a butyl acetate/acetonitrile mixture (4:1). The suspension was heated to 50° C. and 68.2 g (0.812 mol) of sodium hydrogen carbonate was added. A solution of 57.0 g (0.726 mol) of acetyl chloride in 120 ml of butyl acetate was added dropwise over 30 minutes. The reaction mixture was then stirred for a further 40 minutes at 50° C. 190 ml of water was added cautiously and the aqueous phase was separated off and re-extracted with 200 ml of butyl acetate at 50° C. The combined organic extracts were concentrated to 1100 ml and cooled slowly to 2° C. to induce crystallization. The solid was filtered off and rewashed with 100 ml of cold butyl acetate. Recrystallization from 700 ml of butyl acetate gave 183.8 g (92.7%) of the title compound in the form of white crystals. The melting point of the title compound was: 133.5° to 134.6° C. Other data concerning the title compound was:
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]([N:12]=[C:13]=[S:14])=[O:11])=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH3:15][O:16][C:17]1[CH:18]=[C:19]2[C:24](=[CH:25][C:26]=1[O:27][CH3:28])[N:23]=[CH:22][N:21]=[C:20]2[O:29][C:30]1[CH:36]=[CH:35][C:33]([NH2:34])=[CH:32][CH:31]=1.C1(C)C=CC=CC=1>C(O)C>[CH3:15][O:16][C:17]1[CH:18]=[C:19]2[C:24](=[CH:25][C:26]=1[O:27][CH3:28])[N:23]=[CH:22][N:21]=[C:20]2[O:29][C:30]1[CH:36]=[CH:35][C:33]([NH:34][C:13]([NH:12][C:10](=[O:11])[C:7]2[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:9][CH:8]=2)=[S:14])=[CH:32][CH:31]=1
Reactant: O=C(N=C=S)c1ccc([N+](=O)[O-])cc1
Reactant: COc1cc2ncnc(Oc3ccc(N)cc3)c2cc1OC
Solvent: CCO
Solvent: Cc1ccccc1
Product: COc1cc2ncnc(Oc3ccc(NC(=S)NC(=O)c4ccc([N+](=O)[O-])cc4)cc3)c2cc1OC
Temperature: 25 °C
Reaction time: 2 h
Yield: 101.6 %

Procedure:
4-Nitro-1-benzenecarbonyl isothiocyanate (30 mg) was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (74 mg, yield 87%).
Reaction SMILES: C1(COC(=O)[NH:10][CH2:11][C@H:12]2[C@H:16]([OH:17])[CH2:15][N:14]([CH2:18][CH2:19][C:20]3[C:29]4[C:24](=[CH:25][CH:26]=[C:27]([O:30][CH3:31])[N:28]=4)[N:23]=[CH:22][C:21]=3[F:32])[CH2:13]2)C=CC=CC=1>CO.[OH-].[OH-].[Pd+2]>[NH2:10][CH2:11][C@@H:12]1[CH2:13][N:14]([CH2:18][CH2:19][C:20]2[C:29]3[C:24](=[CH:25][CH:26]=[C:27]([O:30][CH3:31])[N:28]=3)[N:23]=[CH:22][C:21]=2[F:32])[CH2:15][C@H:16]1[OH:17]
Reactant: COc1ccc2ncc(F)c(CCN3C[C@@H](CNC(=O)OCc4ccccc4)[C@H](O)C3)c2n1
Agent: [Pd+2]
Agent: [OH-]
Solvent: CO
Product: COc1ccc2ncc(F)c(CCN3C[C@@H](CN)[C@H](O)C3)c2n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 102.5 %

Procedure:
To a solution of (±)-phenylmethyl[(trans-1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-4-hydroxy-3-pyrrolidinyl)methyl]carbamate (1.8 g, 3.96 mmole) in MeOH (100 mL) in a round bottom flask was added Pd(OH)2 (˜100 mg). The reaction contents were stirred under a balloon of H2 overnight at RT. The reaction contents were filtered through Celite® (MeOH) and concentrated to give the title compound (1.3 g, quant.) as a light yellow foam: LC-MS (ES) m/e 321 (M+H)+.
Reaction SMILES: Cl.[O:2]([NH2:4])[CH3:3].[Br:5][C:6]1[CH:7]=[CH:8][C:9]2[C:10]3[N:18]([CH2:19][CH2:20][CH2:21][CH:22]=O)[C:17]([CH2:24][CH2:25][CH3:26])=[N:16][C:11]=3[CH:12]=[N:13][C:14]=2[CH:15]=1>C(O)C>[CH3:3][O:2][N:4]=[CH:22][CH2:21][CH2:20][CH2:19][N:18]1[C:10]2[C:9]3[CH:8]=[CH:7][C:6]([Br:5])=[CH:15][C:14]=3[N:13]=[CH:12][C:11]=2[N:16]=[C:17]1[CH2:24][CH2:25][CH3:26]
Reactant: CON
Reactant: CCCc1nc2cnc3cc(Br)ccc3c2n1CCCC=O
Agent: Cl
Solvent: CCO
Product: CCCc1nc2cnc3cc(Br)ccc3c2n1CCCC=NOC
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Methoxylamine hydrochloride (11.86 g, 142.1 mmol) was added to a solution of 4-(7-bromo-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)butyraldehyde (25.6 g, 71.0 mmol, prepared as described in Example 17 Parts A through D) in ethanol (200 mL). The reaction mixture was stirred at room temperature for 2 hours and then concentrated under reduced pressure. The residue was dissolved in water, neutralized with saturated sodium bicarbonate, and then extracted into dichloromethane. The extract was washed sequentially with saturated sodium bicarbonate and brine, dried over magnesium sulfate, and then concentrated under reduced pressure to provide 27.1 g of 4-(7-bromo-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)butyraldehyde O-methyloxime.