Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:5]1[NH:6][C:7]2[C:12]([C:13]=1[CH2:14][CH:15]=O)=[CH:11][CH:10]=[C:9]([N+:17]([O-:19])=[O:18])[CH:8]=2)([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:21][O:22][C:23](=[O:37])/[CH:24]=[CH:25]/[C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:36][CH2:35][CH2:34][NH:33]2)=[CH:28][CH:27]=1.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O1CCCC1.C(OCC)(=O)C>[CH3:21][O:22][C:23](=[O:37])/[CH:24]=[CH:25]/[C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:36][CH2:35][CH2:34][N:33]2[CH2:15][CH2:14][C:13]2[C:12]3[C:7](=[CH:8][C:9]([N+:17]([O-:19])=[O:18])=[CH:10][CH:11]=3)[NH:6][C:5]=2[C:1]([CH3:2])([CH3:4])[CH3:3])=[CH:28][CH:27]=1
Reactant: COC(=O)/C=C/c1ccc(C2CCCN2)cc1
Reactant: CC(C)(C)c1[nH]c2cc([N+](=O)[O-])ccc2c1CC=O
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: COC(=O)/C=C/c1ccc(C2CCCN2CCc2c(C(C)(C)C)[nH]c3cc([N+](=O)[O-])ccc23)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 57.8 %

Procedure:
To a solution of (2-tert-butyl-6-nitro-1H-indol-3-yl)-acetaldehyde (0.74 g, 2.8 mmol) in tetrahydrofuran (20 mL) was added (E)-3-(4-pyrrolidin-2-yl-phenyl)-acrylic acid methyl ester hydrochloride (0.91 g, 3.4 mmol) and triethylamine (871 μL, 6.26 mmol). The resulting mixture was stirred at room temperature for 1 h and sodium triacetoxyborohydride (0.88 g, 4.0 mmol) was added. The mixture was stirred at room temperature for 16 h, diluted with ethyl acetate, and washed with a saturated sodium bicarbonate and a saturated aqueous solution of sodium chloride. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via silica gel column chromatography to give the title compound (0.77 g, 57%). LCMS (m/z): 476.2539 (M+1).
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl.[CH3:54][O:55][C:56](=[O:65])[CH2:57][CH2:58][CH:59]1[CH2:64][CH2:63][NH:62][CH2:61][CH2:60]1.Br[C:67]1[CH:72]=[CH:71][C:70]([Cl:73])=[CH:69][CH:68]=1>O1CCOCC1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:54][O:55][C:56](=[O:65])[CH2:57][CH2:58][CH:59]1[CH2:64][CH2:63][N:62]([C:67]2[CH:72]=[CH:71][C:70]([Cl:73])=[CH:69][CH:68]=2)[CH2:61][CH2:60]1
Reactant: Clc1ccc(Br)cc1
Reactant: COC(=O)CCC1CCNCC1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cl
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: COC(=O)CCC1CCN(c2ccc(Cl)cc2)CC1
Reaction time: 0.42 h
Yield: 61 %

Procedure:
A mixture of palladium (II) acetate (63 mg; 0.28 mmol), (±)-2,2′-bis-diphenylphosphanyl-[1,1′]binaphthalenyl (258 mg; 0.41 mmol) and cesium carbonate (1.30 g; 4.00 mmol) in dioxane (3 mL) is placed in an ultrasonic bath for 25 minutes. 3-Piperidin-4-yl-propionic acid methyl ester hydrochloride (415 mg; 2.0 mmol, prepared in accordance with Example 138) and 1-bromo-4-chloro-benzene (383 mg; 2.00 mmol) are then added and the reaction mixture is stirred for 2 hours under reflux. New catalyst solution [prepared as above from palladium (II) acetate (63 mg; 0.28 mmol), (±)-2,2′-bis-diphenylphosphanyl-[1,1′]binaphthalenyl (258 mg; 0.41 mmol), cesium carbonate (1.30 g; 4.00 mmol) and dioxane (3 mL)] is prepared with the aid of an ultrasonic bath and added to the reaction mixture. After stirring under reflux for 6 hours, the mixture is diluted with ethyl acetate and is filtered. The filtrate is concentrated under high vacuum and the obtained residue is purified by column chromatography on silica gel (hexanes/dichloromethane 50:50 v/v to 100) to afford the desired compound (345 mg; 1.22 mmol).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[C:13]([N+]([O-])=O)[CH:12]=[C:11]([O:18][CH3:19])[C:10]=1[O:20][CH3:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(C1C=CC=C(OC)C=1OC)(=O)C1C=CC=CC=1.[N+]([O-])(O)=O>C(O)(=O)C>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([O:18][CH3:19])[C:10]=1[O:20][CH3:21])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COc1cc([N+](=O)[O-])cc(OCc2ccccc2)c1OC
Agent: COc1cccc(C(=O)c2ccccc2)c1OC
Solvent: CC(=O)O
Solvent: O=[N+]([O-])O
Product: COc1cccc(OCc2ccccc2)c1OC
Temperature: 0 °C
Reaction time: 2 h

Procedure:
The 1-benzyloxy-2,3-dimethoxy-5-nitrobenzene used as starting material was prepared by treating a solution of 1-benzoyl-2,3-dimethoxybenzene (7.25 g, 29.66 mmol) in glacial acetic acid (15 ml) portionwise with 70% nitric acid (2.84 ml) at room temperature. After 2 h, the reaction mixture was poured into ice-water and extracted with ethyl acetate. The organic phase was washed with 1M NaOH, then brine, dried (MgSO4) and evaporated. The crude product was purified by column chromatography [silica 20% ethyl acetate-hexane] to give, after recrystallisation from CH2Cl2-hexane, the desired product (1.89 g) as a white solid m.p. 101-102°. MS m/z (relative intensity) (M+H)+289 [(M+H),+2%] 91[100%]. 1-Benzyloxy-2,3-dimethoxybenzene was prepared by the method of F Dietl et al Synthesis, 626 (1985).
Reaction SMILES: [CH:1]1([N:7]2[C:11]([CH2:12][CH2:13][CH2:14][O:15][C:16]3[CH:17]=[C:18]4[C:23](=[CH:24][CH:25]=3)[NH:22][C:21](=[O:26])[CH:20]=[CH:19]4)=[N:10][N:9]=[N:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].[CH2:29](Br)[CH:30]=[CH2:31]>CN(C)C=O>[CH2:31]([N:22]1[C:23]2[C:18](=[CH:17][C:16]([O:15][CH2:14][CH2:13][CH2:12][C:11]3[N:7]([CH:1]4[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]4)[N:8]=[N:9][N:10]=3)=[CH:25][CH:24]=2)[CH:19]=[CH:20][C:21]1=[O:26])[CH:30]=[CH2:29]
Reactant: O=c1ccc2cc(OCCCc3nnnn3C3CCCCC3)ccc2[nH]1
Reactant: C=CCBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: C=CCn1c(=O)ccc2cc(OCCCc3nnnn3C3CCCCC3)ccc21
Reaction time: 0.5 h

Procedure:
Into 50 ml of dimethylformamide, 1.8 g of 6-[3-(1-cyclohexyltetrazol-5-yl)propoxy]carbostyril is dissolved, then 0.15 g of NaH is added under stirring for 30 minutes by ice-cooling the outside of the reaction vessel. Into the reaction mixture, 0.52 ml of allyl bromide is added dropwise and stirred at a room temperature for 2 hours. The reaction mixture is then concentrated and the residue is extracted with chloroform, washed with water and dried with Na2SO4. After removal of the drying agent by filtration, the mother liquor is concentrated and the residue is dissolved in chloroform. The chloroform solution is washed with water and then concentrated. The residue thus obtained is purified by a silica gel column chromatography [eluent: chloroform-methanol (50:1)]. The eluted solution is concentrated and the residue is recrystallized from chloroform-petroleum ether to obtain 1.2 g of 1-allyl-6-[3-(1-cyclohexyltetrazol-5-yl)propoxy]carbostyril in the form ofcolorless needle-like crystals. Melting point: 102°-103.5° C.
Reaction SMILES: [H-].[Li+].[Cl:3][C:4]1[CH:21]=[CH:20][C:7]([NH:8][C:9]2[S:10][C:11]3[N:19]=[CH:18][CH:17]=[CH:16][C:12]=3[C:13](=[O:15])[N:14]=2)=[CH:6][CH:5]=1.Br[CH2:23][CH2:24][OH:25]>CN(C=O)C>[Cl:3][C:4]1[CH:21]=[CH:20][C:7]([N:8]=[C:9]2[N:14]([CH2:23][CH2:24][OH:25])[C:13](=[O:15])[C:12]3[CH:16]=[CH:17][CH:18]=[N:19][C:11]=3[S:10]2)=[CH:6][CH:5]=1
Reactant: O=c1nc(Nc2ccc(Cl)cc2)sc2ncccc12
Reactant: OCCBr
Agent: [H-]
Agent: [Li+]
Solvent: CN(C)C=O
Product: O=c1c2cccnc2sc(=Nc2ccc(Cl)cc2)n1CCO
Reaction time: 0.08 h
Yield: 80.6 %

Procedure:
In an atmosphere of argon, a mixture of 60 mg (7.6 mmol) of lithium hydride and 10 ml of DMF was put in a 100 ml flask. To the flask was then connected a dropping funnel which contained 1,600 mg (5.5 mmol) of 2-(4-chloroanilino)-4H-pyrido[3,2-e]-1,3-thiazin-4-one and 10 ml of DMF. The solution of 2-(4-chloroanilino)-4H-pyrido[3,2-e]-1,3-thiazin-4-one was then added dropwise to the aforementioned mixture with stirring in 5 minutes. The mixture was further stirred for 2 hours. To the mixture was then added a mixture of 1,034 mg of 2-bromoethanol and 4 ml of DMF. The mixture was then stirred for 22 hours. After the termination of reaction, the mixture was concentrated under reduced pressure. The resulting residue was then extracted with water and ethyl acetate. The resulting organic phase was separated, washed with water and saturated brine, and then dried over sodium sulfate. The drying agent was then removed by filtration. The filtrate was then concentrated under reduced pressure. The resulting residue was then purified through silica gel column chromatography (eluant: 1/1 mixture of ethyl acetate and normal hexane). As a result, 1.48 g of 2,3-dihydro-2-[(4-chlorophenyl)imino]-3-(2-hydroxyethyl)-4H-pyrido[3,2-e]-1,3-thiazin-4-one was obtained as a low polarity substance, and 220 mg of 2-[N-(4-chlorophenyl)-N-(2-hydroxyethyl)amino]-4H-pyrido[3,2-e]-1,3-thiazin-4-one was obtained as a high polarity substance.
Reaction SMILES: [CH3:1][N:2]1[C:7]2[CH:8]=[C:9]([N:11]3[CH2:16][CH2:15][CH2:14][C@@H:13]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:12]3)[NH:10][C:6]=2[C:5](=[O:25])[N:4]([CH3:26])[C:3]1=[O:27].[Cl:28][C:29]1[CH:36]=[CH:35][CH:34]=[CH:33][C:30]=1[CH2:31]Br.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[Cl:28][C:29]1[CH:36]=[CH:35][CH:34]=[CH:33][C:30]=1[CH2:31][N:10]1[C:6]2[C:5](=[O:25])[N:4]([CH3:26])[C:3](=[O:27])[N:2]([CH3:1])[C:7]=2[CH:8]=[C:9]1[N:11]1[CH2:16][CH2:15][CH2:14][C@@H:13]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:12]1
Reactant: Clc1ccccc1CBr
Reactant: Cn1c(=O)c2[nH]c(N3CCC[C@@H](NC(=O)OC(C)(C)C)C3)cc2n(C)c1=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Cn1c(=O)c2c(cc(N3CCC[C@@H](NC(=O)OC(C)(C)C)C3)n2Cc2ccccc2Cl)n(C)c1=O

Procedure:
A solution of tert-butyl [(3R)-1-(1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)piperidin-3-yl]carbamate (60 mg), 2-chlorobenzyl bromide (32 μl) and potassium carbonate (44 mg) in N,N-dimethylformamide (2 ml) was stirred at room temperature for 2 hours. Water was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure and purified by a preparative thin-layer chromatography (hexane/ethyl acetate=1/2) to obtain the title compound (10 mg) as a white amorphous substance.
Reaction SMILES: [NH2:1][C@H:2]([C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14])[C@@H:3]([CH3:12])[O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[NH:23]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[C@H:24]([C:28](ON1C(=O)CCC1=O)=[O:29])[CH:25]([CH3:27])[CH3:26].CCN(CC)CC>CN(C=O)C>[NH:23]([C:38]([O:40][C:41]([CH3:43])([CH3:42])[CH3:44])=[O:39])[C@H:24]([C:28]([NH:1][C@H:2]([C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14])[C@@H:3]([CH3:12])[O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:29])[CH:25]([CH3:26])[CH3:27]
Reactant: C[C@@H](OCc1ccccc1)[C@H](N)C(=O)OCc1ccccc1
Reactant: CC(C)[C@H](NC(=O)OC(C)(C)C)C(=O)ON1C(=O)CCC1=O
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CC(C)[C@H](NC(=O)OC(C)(C)C)C(=O)N[C@H](C(=O)OCc1ccccc1)[C@@H](C)OCc1ccccc1

Procedure:
H-Thr(Bzl)-OBzl hemioxalate (58 g, 168.4 mmol) was suspended in DMF (700 ml) and stirred with Boc-Val-OSu (48 g, 153.1 mmol) and Et3N (16 ml) at 0° C for 1 hr, 4° C for 72 hrs and 25° C for 24 hrs. It was necessary during this time to add at intervals additional Et3N in order to maintain the pH between 7 and 8. The reaction mixture was worked up as in Example 2 to yield an oil which crystallized from EtOAc with petroleum ether, yield 40.8 g (53.5%); mp 99°-100.5° C; [α]D25 -26.0° (c 1, MeOH). Anal. Calcd for C28H38N2O6 (498.62): C, 67.45; H, 7.68; N, 5.62. Found: C, 67.57; H, 7.55; N, 5.70.
Reaction SMILES: C[O:2][C:3]([C:5]1[C:6](Cl)=[N:7][C:8]2[C:13]([C:14]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[CH:12][C:11]([Cl:21])=[CH:10][C:9]=2[Cl:22])=[O:4].[NH:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1.O>N1C=CC=CC=1>[Cl:21][C:11]1[CH:12]=[C:13]2[C:8](=[C:9]([Cl:22])[CH:10]=1)[N:7]=[C:6]([N:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1)[C:5]([C:3]([OH:2])=[O:4])=[C:14]2[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: C1CCNCC1
Reactant: COC(=O)c1c(Cl)nc2c(Cl)cc(Cl)cc2c1-c1ccccc1
Solvent: O
Solvent: c1ccncc1
Product: O=C(O)c1c(N2CCCCC2)nc2c(Cl)cc(Cl)cc2c1-c1ccccc1
Temperature: 25 °C
Yield: 50.8 %

Procedure:
A solution of 2,6,8-trichloro-4-phenyl-quinoline-3-carboxylic acid methyl ester (115 mg, 0.314 mmol, Eq: 1.00) and piperidine (150 mg, 174 μl, 1.76 mmol, Eq: 5.6) in pyridine (1.5 ml) was stirred at 135° C. for 3 h in a sealed tube. The solution was allowed to cool to RT and cold water and ice were added. A light yellow solid precipitated which was filtered off, washed with water and dried (42 mg, 6,8-dichloro-4-phenyl-2-piperidin-1-yl-quinoline-3-carboxylic acid methyl ester, MS (ESI): 415.3 (M+H)). The mother liquor was evaporated, water was added to the remaining residue and the pH was adjusted to 2 with 0.1N HCl. The mixture was extracted with chloroform and the combined organic extracts were dried with Na2SO4 and evaporated to yield the title compound (64 mg, yellow solid). MS (ESI): 401.2 (M+H)+.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.[CH3:11][NH:12][CH2:13][CH2:14][OH:15]>C(OCC)(=O)C>[CH3:11][N:12]([C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1)[CH2:13][CH2:14][OH:15]
Reactant: CNCCO
Reactant: O=[N+]([O-])c1ccc(F)cc1
Solvent: CCOC(C)=O
Product: CN(CCO)c1ccc([N+](=O)[O-])cc1
Reaction time: 12 h

Procedure:
A mixture of 4-fluoronitrobenzene (20 g) and 2-methylaminoethanol (56 mL) was left to stand for 12 hours and then diluted with ethyl acetate. It was washed with water. The organic phase was dried and concentrated. The product with the molecular weight of 196.21 (C9H12N2O3);
Reaction SMILES: N(C(OCC)=O)=NC(OCC)=O.O[CH2:14][C:15]1[N:16]2[CH:23]=[N:22][CH:21]=[C:17]2[S:18][C:19]=1[CH3:20].[C:24]1(=[O:34])[NH:28][C:27](=[O:29])[C:26]2=[CH:30][CH:31]=[CH:32][CH:33]=[C:25]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[C:24]1(=[O:34])[N:28]([CH2:14][C:15]2[N:16]3[CH:23]=[N:22][CH:21]=[C:17]3[S:18][C:19]=2[CH3:20])[C:27](=[O:29])[C:26]2=[CH:30][CH:31]=[CH:32][CH:33]=[C:25]12
Reactant: Cc1sc2cncn2c1CO
Reactant: O=C1NC(=O)c2ccccc21
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: Cc1sc2cncn2c1CN1C(=O)c2ccccc2C1=O
Temperature: 25 °C
Reaction time: 2 h
Yield: 100 %

Procedure:
Under an argon atmosphere, 1.8 ml of diethyl azodicarboxylate was added dropwise to 30 ml of an anhydrous THF solution containing 962 mg of 3-hydroxymethyl-2-methylimidazo[5,1-b]thiazole, 1.68 g of phthalimide and 3.0 g of triphenylphosphine at room temperature, and the mixture was then stirred at room temperature for 2 hours as it was. The solvent was evaporated under reduced pressure, and the resulting residue was purified through a silica gel column chromatograph to obtain 1.7 g of 3-phthalimidomethyl-2-methylimidazo[5,1-b]thiazole.
Reaction SMILES: [CH3:1][N:2]([CH:13]1[CH2:21][C:20]2[C:15](=[CH:16][CH:17]=[C:18]([N+:22]([O-])=O)[CH:19]=2)[CH2:14]1)[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([N+:10]([O-])=O)=[CH:6][CH:5]=1>C(OCC)(=O)C.[Pd]>[NH2:22][C:18]1[CH:19]=[C:20]2[C:15](=[CH:16][CH:17]=1)[CH2:14][CH:13]([N:2]([CH2:3][C:4]1[CH:5]=[CH:6][C:7]([NH2:10])=[CH:8][CH:9]=1)[CH3:1])[CH2:21]2
Reactant: CN(Cc1ccc([N+](=O)[O-])cc1)C1Cc2ccc([N+](=O)[O-])cc2C1
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CN(Cc1ccc(N)cc1)C1Cc2ccc(N)cc2C1
Temperature: 25 °C
Reaction time: 1 h
Yield: 58.6 %

Procedure:
2-[N-Methyl-N-(4-nitrobenzyl)amino]-5-nitroindane (2.3 g) in ethyl acetate (60 ml) containing 5% Pd/C (. . . g) was stirred under a hydrogen atmosphere [206.8 kPa (30 psi)] for 1 hour at room temperature. The catalyst was then removed by filtration and the filtrate was evaporated to dryness in vacuo. The residue was purified by column chromatography on silica eluting with methylene chloride containing methanol (0% up to 1%). The product-containing fractions were combined and evaporated to give the title compound (1.1 g) as an oil which was used directly without further purification.
Reaction SMILES: C([O:3][C:4](=O)[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][S:11]([C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=1)=[O:12])C.[NH2:21][OH:22].[OH-].[K+].CO>C1COCC1>[OH:22][NH:21][C:4](=[O:3])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][S:11]([C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=1)=[O:12]
Reactant: CCOC(=O)CCCCCCS(=O)c1ccc(Cl)cc1
Reactant: NO
Agent: [K+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: O=C(CCCCCCS(=O)c1ccc(Cl)cc1)NO
Temperature: 0 °C
Reaction time: 1 h
Yield: 82.3 %

Procedure:
To a solution of 7-(4-chloro-benzenesulfinyl)-heptanoic acid ethyl ester (0.5 g, 1.6 mmol) in distilled THF (10 mL) containing 50% aqueous hydroxylamine (0.9 mL, 13.6 mmol) was added at 0° C. a solution of potassium hydroxide in methanol (2.5 mL, 1M, 2.5 mmol) in a dropwise manner. After stirring at 0° C. for 1 h, distilled water (10 mL) was added and the mixture was made neutral by dropwise addition of concentrated hydrochloric acid (10 M) at 0° C. The aqueous solution was extracted with ethyl acetate (2×25 mL) and the combined extracts were washed with brine (25 mL), dried over anhydrous MgSO4, filtered and evaporated to dryness. The residue was recrystallised from ethyl acetate to give the title compound (0.4 g, 83%) as a white powder, mp 103-105° C.
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4]1[C:8](=[O:9])[C:7]2=[CH:10][CH:11]=[CH:12][CH:13]=[C:6]2[C:5]1=[O:14].C(N(CC)CC)C.S(=O)(=O)=O.N1C=CC=CC=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CS(C)=O.C(Cl)Cl>[O:14]=[C:5]1[C:6]2[C:7](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8](=[O:9])[N:4]1[CH2:3][CH:2]=[O:1]
Reactant: O=C1c2ccccc2C(=O)N1CCO
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: O=S(=O)=O
Solvent: CS(C)=O
Solvent: ClCCl
Solvent: c1ccncc1
Product: O=CCN1C(=O)c2ccccc2C1=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 31.7 %

Procedure:
To a solution of N-(2-hydroxyethyl)phthalimide (1.92 g, 10 mmol) and triethylamine (7 mL, 50 mmol) in DMSO (25 mL) was added solid pyridine sulfur trioxide (4.8 g, 30 mmol) by portions. The resulting mixture was stirred at room temperature for 1 h. The reaction mixture is poured into a mixture of CH2Cl2 and 0.5N aq. citric acid. The layers were separated and the organic layer was washed with water and brine. The organic phase was dried (Na2SO4), and the solvent was removed in vacuo. The resultant residue was purified by flash chromatography (SiO2, 1:1 ethyl acetate/hexane) to provide the title compound (0.6 g, 32%). MS 190 (M+H)+.
Reaction SMILES: [C:1]1([CH:11]=O)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.CCCCCC.[CH2:19]([O:21][C:22](=[O:24])[CH3:23])[CH3:20]>C(#N)C.O1CCCC1.C(OC(=O)C)C>[CH2:19]([O:21][C:22](=[O:24])[CH:23]=[CH:11][C:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1)[CH3:20]
Reactant: CCOC(C)=O
Reactant: O=Cc1cccc2ccccc12
Solvent: CCCCCC
Solvent: CC#N
Solvent: C1CCOC1
Product: CCOC(=O)C=Cc1cccc2ccccc12
Reaction time: 8 h
Yield: 90 %

Procedure:
22.4 g(0.10 mol) of triethylphosphonoacetate was dissolved in 500 ml of acetonitrile and 30.4 g(2mol) of 1,8-diazabicyclo[5.4.0]undec-7-ene (1,5-5)(DBU) was slowly added thereto. 15.6 g(0.10 mol) of 1-naphthaldehyde dissolved in 20 ml of tetrahydrofuran was slowly added to the above reaction solution and the resulting mixture was stirred for 8 hours. The organic solvent was removed under reduced pressure, the residue thus obtained was dissolved in ethylacetate, washed twice with water, dried over magnesium sulfate and concentrated. The residue was subjected to column chromatography(eluent: n-hexane/ethylacetate=95/5, v/v) to give 20.3 g(0.090 mol, Yield 90%) of the title compound.
Reaction SMILES: O.Cl.[OH:3][CH2:4][C:5]1[N:6]=[N:7][N:8]([CH3:10])[CH:9]=1.[Si:11](Cl)([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12].CCN(CC)CC>CN(C)C1C=CN=CC=1.C(Cl)Cl>[Si:11]([O:3][CH2:4][C:5]1[N:6]=[N:7][N:8]([CH3:10])[CH:9]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: Cn1cc(CO)nn1
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: O
Product: Cn1cc(CO[Si](C)(C)C(C)(C)C)nn1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 4-hydroxymethyl-1-methyl-1H-[1,2,3]triazole hydrochloride hydrate (WO-A-9850385) (7.0 g, 41.8 mmol), tert-butyldimethylsilyl chloride (6.3 g, 41.8 mmol), Et3N (11.6 ml, 83.6 mmol) and 4-(dimethylamino)pyridine (255 mg, 5 mol %) in CH2Cl2 (250 ml) was stirred at room temperature overnight under N2. Iso-hexanes (400 ml) were added and the resulting precipitate was removed by filtration. The filtrate was concentrated under reduced pressure and the mixture was purified by column chromatography on silica using 10-100% Et2O/iso-hexanes as eluent to yield the desired protected alcohol (8.90 g, 94%). 1H NMR (360 MHz, CDCl3) δ 7.35 (1H, s), 4.73 (2H, s), 3.98 (3H, s), 0.81(9H, s), 0.00 (6H, s).
Reaction SMILES: [Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH2:11][CH:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)=[C:4](Cl)[N:3]=1.[NH3:19]>CC(O)C>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH2:11][CH:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)=[C:4]([NH2:19])[N:3]=1
Reactant: Clc1nc(Cl)c2ncn(CC3CCOCC3)c2n1
Reactant: N
Solvent: CC(C)O
Product: Nc1nc(Cl)nc2c1ncn2CC1CCOCC1

Procedure:
2,6-dichloro-9-(tetrahydro-2H-pyran-4-ylmethyl)-9H-purine (3.08 g, containing triphenylphosphine oxide) was heated with 2M ammonia in IPA (50 mL) at 50° C., overnight. The reaction mixture was then evaporated to dryness to give a yellow solid. This material (3.2089 g) was recrystallised using methanol (50 mL) and after cooling the resultant solid was filtered and washed with methanol (5 mL) to give the title compound (1.5554 g). The filtrate was evaporated and recrystallised from methanol (25 mL) and after cooling the resultant solid was filtered to give a second crop (0.2324 g) and was consistent with first batch by NMR and LCMS.
Reaction SMILES: [N:1]1([C@@H:10]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)[C@H:11]([OH:14])[CH2:12]O)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.[CH2:22]([N:24](CC)CC)C.C1(C)C=CC(S(Cl)(=O)=O)=CC=1.CN.C(O)C>ClCCl>[F:21][C:17]1[CH:16]=[C:15]([C@H:10]([N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[CH:3]=[CH:2]2)[C@H:11]([OH:14])[CH2:12][NH:24][CH3:22])[CH:20]=[CH:19][CH:18]=1
Reactant: CCN(CC)CC
Reactant: OC[C@@H](O)[C@H](c1cccc(F)c1)N1CCc2ccccc21
Agent: CN
Agent: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: ClCCl
Solvent: CCO
Product: CNC[C@@H](O)[C@H](c1cccc(F)c1)n1ccc2ccccc21
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a solution of (2S,3S)-3-(2,3-dihydro-1H-indol-1-yl)-3-(3-fluorophenyl)propane-1,2-diol (452 mg, 1.586 mmol) in dichloromethane (3 mL) under nitrogen was added triethylamine (1.1 mL, 7.93 mmol). The mixture was cooled to 0° C., and para-toluenesulfonyl chloride (423 mg, 2.22 mmol) was added portionwise. The reaction mixture was stirred at 0° C. for 1 hour and stored at 0° C. overnight. Methylamine in absolute ethanol (8 M, 5 mL, 40 mmol) was added and the reaction mixture was sealed, and stirred overnight while warming to room temperature. All volatiles were removed under reduced pressure. The oil residue was dissolved in dichloromethane (20 mL), washed with aqueous potassium carbonate (5 mL), dried (anhydrous sodium sulfate), and concentrated. Purification by Biotage chromatography (FlasH12i, silica, 0-15% MeOH/dichloromethane/0.5% triethylamine) gave (1S,2R)-1-(3-fluorophenyl)-1-(1H-indol-1-yl)-3-(methylamino)propan-2-ol, which was dissolved dichloromethane (5 mL) and treated with a 1 M ethereal solution of hydrochloric acid (1.9 mL, 1.9 mmol). To the resulting solution was added hexane until white powder formed, which was collected, washed with hexane, and dried in vacuo to yield 209 mg (44%) of (1S,2R)-1-(3-fluorophenyl)-1-(1H-indol-1-yl)-3-(methylamino)propan-2-ol hydrochloride as a white powder. MS (ES) m/z 299.0 ([M+H]+); HRMS: calcd for C18H19FN2O+H+, 299.1554; found (ESI, [M+H]+), 299.1553.