Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Na].[CH2:2](O)[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][OH:8].[C:10]([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([CH3:23])([CH3:22])[CH3:21])[C:15]=1[OH:24])([CH3:13])([CH3:12])[CH3:11].Cl>>[C:20]([C:16]1[CH:17]=[C:18]([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][OH:8])[CH:19]=[C:14]([C:10]([CH3:13])([CH3:12])[CH3:11])[C:15]=1[OH:24])([CH3:23])([CH3:22])[CH3:21]
Reactant: CC(C)(C)c1cccc(C(C)(C)C)c1O
Reactant: OCCCCCCO
Agent: Cl
Agent: [Na]
Product: CC(C)(C)c1cc(CCCCCCO)cc(C(C)(C)C)c1O
Temperature: 225 °C
Yield: 66.6 %

Procedure:
To 1.15 grams of metallic sodium (0.05 moles) was added to 59 grams of 1,6-hexanediol (0.5 moles) in a 250 ml flask fitted with a water trap and the mixture was stirred until the sodium dissolved. There was then added 20.6 grams of 2,6-di-tert.-butylphenol (0.1 mole) and the mixture was heated for 7.5 hours at 225° C. The mixture was allowed to cool and the base was neutralized by the addition of 5 ml. of concentrated hydrochloric acid. Sodium chloride from neutralization of the base was removed by filtration and the filtrate was distilled under vacuum. There was obtained 20.4 grams (66.6% yield) of 6-(3,5-di-tert.-butyl-4-hydroxyphenyl)hexanol.
Reaction SMILES: [ClH:1].Cl.[C:3]([C:6]1[CH:39]=[CH:38][C:9]2[S:10][C:11]([CH2:13][C:14]([C:33]([O:35][CH2:36][CH3:37])=[O:34])([C:20]3[CH:25]=[CH:24][C:23]([O:26][CH2:27][C@H:28]4[CH2:32][CH2:31][CH2:30][NH:29]4)=[CH:22][CH:21]=3)[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:12][C:8]=2[CH:7]=1)(=[NH:5])[NH2:4].Cl.[C:41](=[NH:46])(OCC)[CH3:42].C(N(CC)CC)C>C(O)C>[ClH:1].[ClH:1].[C:41]([N:29]1[CH2:30][CH2:31][CH2:32][C@@H:28]1[CH2:27][O:26][C:23]1[CH:22]=[CH:21][C:20]([C:14]([C:33]([O:35][CH2:36][CH3:37])=[O:34])([CH2:13][C:11]2[S:10][C:9]3[CH:38]=[CH:39][C:6]([C:3](=[NH:4])[NH2:5])=[CH:7][C:8]=3[CH:12]=2)[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:25][CH:24]=1)(=[NH:46])[CH3:42]
Reactant: CCOC(C)=N
Reactant: CCOC(=O)C(Cc1cc2cc(C(=N)N)ccc2s1)(C(=O)OCC)c1ccc(OC[C@H]2CCCN2)cc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCO
Product: CCOC(=O)C(Cc1cc2cc(C(=N)N)ccc2s1)(C(=O)OCC)c1ccc(OC[C@H]2CCCN2C(C)=N)cc1
Temperature: 25 °C

Procedure:
1.0 g of ethyl 3-(5-amidinobenzo[b]thien-2-yl)-2-ethoxycarbonyl-2-[4-[((2R)-2-pyrrolidinyl)methoxy]phenyl]propionate dihydrochloride was dissolved in 20 ml of ethanol, followed by the addition of 0.42 g of ethyl acetimidate hydrochloride. 0.51 g of triethylamine was added to the thus prepared solution during stirring under ice cooling, and the resulting mixture was warmed up to room temperature and stirred for 18 hours. Thereafter, the solvent was distilled off to obtain ethyl 2-[4-[((2R)-1-acetimidoyl-2-pyrrolidinyl)methoxy]phenyl]-2-ethoxycarbonyl-3-(5-amidinobenzo[b]thien-2-yl)propionate dihydrochloride. The thus obtained ester compound was dissolved in 50 ml of 5N hydrochloric acid and refluxed under heating for 60 minutes. After distilling off the solvent, the resulting residue was subjected to column chromatography using a column packed with a highly porous polymer type synthetic adsorbent (styrene-divinylbenzene polymer: Diaion HP-20) and using a water/acetonitrile mixture as an elution solvent. Fractions of interest were pooled and concentrated, and the resulting residue was subjected to reversed phase high performance liquid chromatography using a column packed with octadecyl-bonded silica gel and using a water/acetonitrile mixture as an elution solvent. Thereafter, the thus eluted fractions of interest were pooled, mixed with dilute hydrochloric acid, and then concentrated to dryness. In this way, 360 mg of the title compound was obtained in the form of a light yellow solid.
Reaction SMILES: O=[O+][O-].[C:4]1([CH2:10][O:11][C:12](=[O:18])[CH:13]([CH3:17])[CH2:14][CH:15]=C)[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.O=O.C(O)(=[O:23])C>CO.[Zn]>[C:4]1([CH2:10][O:11][C:12](=[O:18])[CH:13]([CH3:17])[CH2:14][CH:15]=[O:23])[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: CC(=O)O
Reactant: C=CCC(C)C(=O)OCc1ccccc1
Agent: O=O
Agent: O=[O+][O-]
Agent: [Zn]
Solvent: CO
Product: CC(CC=O)C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 100 %

Procedure:
A stream of ozone is passed through a -78° C. solution of 1.0 g of racemic 2-methyl-4-pentenoic acid phenylmethyl ester in 110 ml of methyl alcohol until the blue color persists. The excess ozone is discharged by a stream of oxygen, followed by argon. One gram of zinc dust and 1.0 g of acetic acid is added and the resulting mixture allowed to warm to room temperature; followed by stirring for 1 hour. The excess zinc is removed by filtration and the filtrate is concentrated in vacuo. The residue is extracted with diethyl ether, filtered and the filtrate concentrated in vacuo. The residue is purified by pad filtration (silica gel, 50% diethyl ether/petroletum ether) to give 1.01 g of racemic 2-methyl-4-oxobutanoic acid phenylmethyl ester.
Reaction SMILES: [O-]CC.[Na+].[C:5]([O:12][CH2:13][CH3:14])(=[O:11])[C:6]([O:8]CC)=O.[F:15][C:16]1[CH:17]=[C:18]([C:22](=[O:24])[CH3:23])[CH:19]=[CH:20][CH:21]=1>C(O)C>[F:15][C:16]1[CH:17]=[C:18]([C:22](=[O:24])[CH2:23][C:6](=[O:8])[C:5]([O:12][CH2:13][CH3:14])=[O:11])[CH:19]=[CH:20][CH:21]=1
Reactant: CC(=O)c1cccc(F)c1
Reactant: CCOC(=O)C(=O)OCC
Agent: CC[O-]
Agent: [Na+]
Solvent: CCO
Product: CCOC(=O)C(=O)CC(=O)c1cccc(F)c1
Reaction time: 0.17 h
Yield: 72.5 %

Procedure:
To a solution of sodium ethoxide (123 g, 362 mmol) in ethanol (300 mL) at 0° C. was added a solution of diethyl oxalate (49.4 mL, 362 mmol) in ethanol (25 mL) and the resulting solution was stirred for 10 min. 1-(3-Fluorophenyl)ethanone (50 g, 362 mmol) in ethanol (25 mL) was added and the reaction mixture was stirred at room temperature for 16 h. Ethanol was distilled off under reduced pressure and the residue obtained was quenched with ice cold water and the brown product was filtered. This crude product was purified by ISCO using 220 g silica gel column and 20% ethyl acetate in hexane as eluent. The combined fractions were concentrated to afford Intermediate 4A (62.5 g, 73%). MS(ES): m/z=239 [M+H]+; 1H NMR (400 MHz, CDCl3) δ ppm 15.13 (bs, 1H), 7.77-7.83 (m, 1H), 7.67-7.73 (m, 1H), 7.51 (td, J=8.03, 5.48 Hz, 1H), 7.29-7.37 (m, 1H), 7.28 (s, 1H), 4.43 (q, J=7.18 Hz, 2H), 1.40-1.47 (m, 3H).
Reaction SMILES: [C:1]([O:5][C:6](=[O:24])[CH2:7][C:8](=[O:23])[CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:13][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:28][CH2:29][O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32]>CN(C)C=O>[C:14]1([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:13]=[CH:12][C:11]([CH2:10][CH2:9][C:8](=[O:23])[CH:7]([CH2:28][CH2:29][O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])[C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:24])=[CH:16][CH:15]=1
Reactant: CC(C)(C)[Si](C)(C)OCCBr
Reactant: CC(C)(C)OC(=O)CC(=O)CCc1ccc(-c2ccccc2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)C(CCO[Si](C)(C)C(C)(C)C)C(=O)CCc1ccc(-c2ccccc2)cc1
Temperature: 70 °C
Yield: 59.1 %

Procedure:
A solution of 5-biphenyl-4-yl-3-oxo-pentanoic acid tert-butyl ester (13.7 g, 42.4 mmol) in dimethylformamide (10 mL) was added dropwise over 20 min to a stirred suspension of sodium hydride (60% mineral oil suspension; 1.78 g, 44.4 mmol) in dimethylformamide (10 mL) at 0° C. under nitrogen. After stirring for 20 min (2-bromoethoxy)-t-butyldimethylsilane (10.0 g, 46.4 mmol) was added dropwise over 20 min at 0° C. then the reaction heated to 70° C. for 2.5 h. On cooling to room temperature the reaction was quenched by careful addition of water (5 mL) then the volatiles evaporated. The residue was partitioned between saturated aqueous ammonium chloride solution (200 mL) and dichloromethane (200 mL) and the phases separated. The aqueous phase was washed with dichloromethane (3×200 mL) then the organic phases combined, washed with brine (200 mL), dried (sodium sulfate) and the solvent evaporated. The residue was chromatographed on silica gel (10% diethyl ether:cyclohexane) to give the title compound (12.1 g, 59%) as colourless oil which was a mixture of diastereomers. LC/MS: 4.70 min; z/e 483, calcd (M+1) 483. 1H NMR (400 MHz: CDCl3): 7.55 (2H), 7.50 (2H), 7.40 (2H), 7.35 (1H), 7.25 (2H), 3.60 (2H), 2.95 (3H), 2.20 (1H minor) 2.0 (1H major), 1.55 (1H), 1.45 (11H), 0.85 (9H), 0.5 (6H).
Reaction SMILES: N#N.[CH:3]1([C:6]2[S:7][C:8]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[C:9]([C:11](O)=[O:12])[N:10]=2)[CH2:5][CH2:4]1.CN(C=O)C.C(Cl)(=O)C([Cl:28])=O>C1(C)C=CC=CC=1>[CH:3]1([C:6]2[S:7][C:8]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[C:9]([C:11]([Cl:28])=[O:12])[N:10]=2)[CH2:5][CH2:4]1
Reactant: O=C(Cl)C(=O)Cl
Reactant: O=C(O)c1nc(C2CC2)sc1-c1ccccc1
Agent: N#N
Solvent: CN(C)C=O
Solvent: Cc1ccccc1
Product: O=C(Cl)c1nc(C2CC2)sc1-c1ccccc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a suspension of 2-cyclopropyl-5-phenyl-thiazole-4-carboxylic acid (90 mg, 0.37 mmol) in toluene (2.0 mL) was treated with a drop of DMF followed by oxalyl chloride (0.11 mL, 1.25 mmol) and the resulting yellow solution was stirred at rt for 2 h. The solvent was then removed under reduced pressure (coevaporation with toluene) to give 2-cyclopropyl-5-phenyl-thiazole-4-carbonyl chloride.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH2:9][CH3:10])=[CH:4][C:3]=1[O:12][CH3:13].[Cl:14][CH2:15][CH2:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]([C:26]2[CH:31]=[CH:30][C:29]([OH:32])=[CH:28][CH:27]=2)=O)=[CH:20][CH:19]=1>>[Cl:14][CH2:15][CH2:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]([C:26]2[CH:31]=[CH:30][C:29]([OH:32])=[CH:28][CH:27]=2)=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([OH:1])=[C:3]([O:12][CH3:13])[CH:4]=2)[CH2:9][CH3:10])=[CH:20][CH:19]=1
Reactant: O=C(c1ccc(O)cc1)c1ccc(OCCCl)cc1
Reactant: CCC(=O)c1ccc(O)c(OC)c1
Product: CCC(=C(c1ccc(O)cc1)c1ccc(OCCCl)cc1)c1ccc(O)c(OC)c1
Yield: 38.5 %

Procedure:
Following general procedure of McMurry reaction as example 1, step B described, 1-(4-hydroxy-3-methoxyphenyl)propan-1-one (207 mg, 1.15 mmol) was reacted with (4-(2-chloroethoxy)phenyl)(4-hydroxyphenyl)methanone (318 mg, 1.15 mmol) to give 188 mg desired product (38.5% yield).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)[CH2:10][N:11]1[C:16](=[O:17])[C:15]([N:18]2[CH2:23][CH2:22][N:21]([CH2:24][C:25]3[CH:26]=[C:27]([CH:31]=[CH:32][CH:33]=3)[C:28](O)=[O:29])[CH2:20][CH2:19]2)=[C:14]([CH3:34])[N:13]([CH2:35][C:36]2[C:41]([C:42]([F:45])([F:44])[F:43])=[CH:40][CH:39]=[CH:38][C:37]=2[F:46])[C:12]1=[O:47])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl-].[CH2:55]([O:57][C:58](=[O:63])[CH2:59][CH2:60][CH2:61][NH2:62])[CH3:56].C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH2:55]([O:57][C:58](=[O:63])[CH2:59][CH2:60][CH2:61][NH:62][C:28](=[O:29])[C:27]1[CH:31]=[CH:32][CH:33]=[C:25]([CH2:24][N:21]2[CH2:22][CH2:23][N:18]([C:15]3[C:16](=[O:17])[N:11]([CH2:10][C@H:9]([NH:8][C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[C:48]4[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=4)[C:12](=[O:47])[N:13]([CH2:35][C:36]4[C:41]([C:42]([F:44])([F:45])[F:43])=[CH:40][CH:39]=[CH:38][C:37]=4[F:46])[C:14]=3[CH3:34])[CH2:19][CH2:20]2)[CH:26]=1)[CH3:56]
Reactant: CCOC(=O)CCCN
Reactant: Cc1c(N2CCN(Cc3cccc(C(=O)O)c3)CC2)c(=O)n(C[C@H](NC(=O)OC(C)(C)C)c2ccccc2)c(=O)n1Cc1c(F)cccc1C(F)(F)F
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: [Cl-]
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)CCCNC(=O)c1cccc(CN2CCN(c3c(C)n(Cc4c(F)cccc4C(F)(F)F)c(=O)n(C[C@H](NC(=O)OC(C)(C)C)c4ccccc4)c3=O)CC2)c1
Yield: 99.7 %

Procedure:
To a solution of 3-{4-[3-((R)-2-tert-butoxycarbonylamino-2-phenyl-ethyl)-1-(2-fluoro-6-trifluoromethyl-benzyl)-6-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl]-piperazin-1-ylmethyl}-benzoic acid (40 mg, 0.0541 mmol) and 4-amino-butyric acid ethyl ester chloride (19 mg, 0.108 mmol) in DMF (0.5 mL) was added N,N-diisopropylethylamine(38 μl, 0.216 mmol), after which HBTU (51 mg, 0.162 mmol) was added to the solution, with stirring. The solution was concentrated at room temperature for 6 hrs, with stirring. The residue was diluted in EtOAc and washed with an aqueous saturated sodium bicarbonate solution, an aqueous saturated ammonium chloride solution, and an aqueous saturated sodium chloride solution in that order. After being separated, the organic layer was dried over sodium sulfate, filtered and concentrated. The residue was purified using silica gel chromatography (eluent: dichloromethane/methanol, 30/1) and dried in a vacuum to afford 46 mg of the compound as a yellowish solid (yield 99%). 1H NMR (300 MHz, CDCl3) δ 1.24 (3H, t), 1.34 (9H, s), 1.98 (2H, pentet), 2.31 (2H, m), 2.34 (3H, s), 2.44 (2H, t), 2.53 (2H, m), 2.82 (2H, m), 3.53 (2H, q), 3.64 (4H, m), 4.06 (1H, m), 4.12 (2H, q), 4.24 (1H, t), 5.00 (1H, m), 5.45 (2H, dd), 5.78 (1H, m), 6.30 (0.2H, t), 6.77 (0.8H, t), 7.20-7.41 (8H, m), 7.53 (2H, t), 7.83 (1H, d), 7.71 (1H, d), 7.75 (1H, s)
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[CH2:13][CH2:12][CH2:11][C:10]1=[O:14].[C:15](Cl)([N:17]=[C:18]=[O:19])=[O:16].C1(C)C=CC=CC=1>C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[C:10]2[O:14][C:18](=[O:19])[NH:17][C:15](=[O:16])[C:11]=2[CH2:12][CH2:13]1
Reactant: O=C1CCCC1c1ccc(F)cc1F
Reactant: O=C=NC(=O)Cl
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: O=c1[nH]c(=O)c2c(o1)C(c1ccc(F)cc1F)CC2
Temperature: 120 °C
Yield: 36.4 %

Procedure:
A mixture of 2-(2,4-difluorophenyl)cyclopentanone (1.014 g, 5.17 mmol) and 50% wt. carbonisocyanatidic chloride solution in toluene (1.963 g, 9.30 mmol) was heated at 58° C. for 1 h and at 120° C. for 3 h. The reaction mixture was dissolved in ethyl acetate and washed with an aqueous solution of sodium bicarbonate. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were dried over anhydrous magnesium sulfate and filtered. The solvent was removed in vacuum and the residue was purified by column chromatography on silica gel to give 7-(2,4-difluorophenyl)-6,7-dihydrocyclopenta[e][1,3]oxazine-2,4(3H,5H)-dione (499.3 mg, 1.883 mmol, 36.4% yield) as brown solid. LC-MS (M+H)+=265.1.
Reaction SMILES: C(O[C:9]1[CH:17]=[CH:16][C:15](CCOS(C2C=CC(C)=CC=2)(=O)=O)=[CH:14][C:10]=1[C:11]([NH2:13])=[O:12])C1C=CC=CC=1>CO.O1CCCC1.[C].[Pd]>[C:11]([NH2:13])(=[O:12])[C:10]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:9]=1
Reactant: Cc1ccc(S(=O)(=O)OCCc2ccc(OCc3ccccc3)c(C(N)=O)c2)cc1
Agent: [Pd]
Solvent: CO
Solvent: C1CCOC1
Product: NC(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 260.5 %

Procedure:
2-Benzyloxy-5-[2-(p-toluenesulfonyloxy)ethyl]benzamide (627 mg) was dissolved in methanol (5 ml) and tetrahydrofuran (5 ml), and 10% palladium carbon (wet, 50% water) (169 mg) was added to the solution. The mixture was stirred for 1 hour at room temperature under a hydrogen atmosphere, and the catalyst was filtered off. Removal of the solvent under reduced pressure gave 2-hydroxy-5-[2-toluenesulfonyloxy)ethyl]benzamide (465 mg).
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[C:9]([O:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]([NH:17][S:18]([CH3:21])(=[O:20])=[O:19])=[O:16])[C:4]=2[CH:3]=C1.C[OH:23]>>[CH:3]([C:4]1[C:5]([OH:1])=[CH:6][CH:7]=[CH:8][C:9]=1[O:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]([NH:17][S:18]([CH3:21])(=[O:20])=[O:19])=[O:16])=[O:23]
Reactant: CS(=O)(=O)NC(=O)CCCCOc1cccc2occc12
Reactant: CO
Product: CS(=O)(=O)NC(=O)CCCCOc1cccc(O)c1C=O
Temperature: -65 °C

Procedure:
5-(4-Benzofuranyloxy)-N-methylsulphonylpentanamide (0.933 g, 0.003 M) was dissolved in dry methanol (135 ml) and cooled to -65° C. with stirring and exclusion of moisture. Ozonised air was bubbled through the solution at a rate of 20 liters/hr for 45 mins. Nitrogen was then bubbled through the solution (5 mins) to remove excess ozone before the addition of dimethyl sulphide (0.9 ml). The mixture was allowed to warm to room temperature overnight (16 hr). The solvent was removed in vacuo, the residue dissolved in ethyl acetate-ether (1:1), washed with water and extracted with 5% sodium bicarbonate solution. The combined extracts were acidified with concentrated hydrochloric acid the precipitated solid was filtered off, washed wall with water and recrystallised from ethyl acetate-petrol to give 5-(2-formyl-3-hydroxyphenoxy)-N-methylsulphonylpentanamide, m.p. 136°-138° C. (Found: C, 49.54; H, 5.33; N. 4.12, S, 10.14. C13H17NSO6 requires C, 49.51; H, 5.43; N, 4.44; S, 10.17%).
Reaction SMILES: [O:1]=[S:2]1(=[O:15])[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.[CH2:16]([CH:26]1[CH2:28][O:27]1)[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25]>[Br-].C([P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)C>[O:15]=[S:2]1(=[O:1])[CH2:3][CH2:4][N:5]([C:8]2[CH:9]=[CH:10][C:11]([O:14][CH2:28][CH:26]([OH:27])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])=[CH:12][CH:13]=2)[CH2:6][CH2:7]1
Reactant: O=S1(=O)CCN(c2ccc(O)cc2)CC1
Reactant: CCCCCCCCCCC1CO1
Agent: CC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Product: CCCCCCCCCCC(O)COc1ccc(N2CCS(=O)(=O)CC2)cc1
Yield: 38.9 %

Procedure:
4-(1,1-dioxo-thiomorpholin-4-yl)phenol (2.3 g, 10 mmol), 2-(decyl)-oxirane (1.9 g, 10 mmol) and ethyltriphenylphosphonium bromide (0.2 g) are reacted and purified as described for compound 102 to afford a light brown solid 1.6 g (38%), m.p. 84° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:13](=[CH:14][CH:15]=1)[NH:12][C:11]1[CH2:10][CH2:9][CH:8]([NH:16][C:17](=[O:21])[CH:18]([CH3:20])[CH3:19])[CH2:7][C:6]2=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].Cl.Cl[CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=1>O1CCCC1.C1COCC1.CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:13](=[CH:14][CH:15]=1)[N:12]([CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=1)[C:11]1[CH2:10][CH2:9][CH:8]([NH:16][C:17](=[O:21])[CH:18]([CH3:19])[CH3:20])[CH2:7][C:6]2=1
Reactant: COc1ccc2[nH]c3c(c2c1)CC(NC(=O)C(C)C)CC3
Reactant: ClCc1ccccn1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: Cl
Agent: [K+]
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: COc1ccc2c(c1)c1c(n2Cc2ccccn2)CCC(NC(=O)C(C)C)C1
Reaction time: 0.5 h
Yield: 75.3 %

Procedure:
Dissolve N-(6-methoxy-2,3,4,9-tetrahydro-1H-carbazol-3-yl)-isobutyramide (200 mg, 0.70 mmol) in anhydrous tetrahydrofuran (6 mL) under nitrogen. Add dropwise potassium bis(trimethylsilyl)amide (3.2 mL, 1.6 mmol, 0.5M in toluene) and stir 30 min. Add slowly 2-(chloromethyl)pyridine hydrochloride (131 mg, 0.80 mmol) in THF/DMF (0.4 mL/1.3 mL) and stir at ambient temperature for 18 h. Quench with saturated ammonium chloride solution (0.5 mL) and partition between ethyl acetate and water. Separate the two phases and wash the aqueous phase with ethyl acetate (2×). Dry the combined organic portions (MgSO4), filter, and concentrate in vacuo to obtain a residue. Purify the material by silica gel chromatography, eluting with 50% ethyl acetate/dichloromethane with a gradient up to 80% ethyl acetate/dichloromethane to obtain 199 mg (75%) of a light yellow solid. MS (ES): m/z 378 (M+1); 1H NMR(DMSO-d6): δ 8.50 (dd, 1H, J=4.8, 0.9 Hz), 7.82 (d, 1H, J=7.5 Hz), 7.65 (dt, 1H, J=7.6, 1.6 Hz), 7.22 (m, 2H), 6.89 (d, 1H, J=2.2 Hz), 6.77 (d, 1H, J=7.9 Hz), 6.63 (dd, 1H, J=8.6, 2.4 Hz), 5.32 (s, 2H), 3.97 (m, 1H), 3.72 (s, 3H), 2.91 (dd, 1H, J=15.0, 5.3 Hz), 2.85-2.76 (m, 1H), 2.74-2.64 (m, 1H), 2.45 (m, 1H), 2.37 (m, 1H), 1.94 (m, 1H), 1.77 (m, 1H), 0.99 (m, 6H).
Reaction SMILES: [C:1]1([CH2:7][C:8]([N:10]2[C@@H:14]([CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:13][O:12][C:11]2=[O:22])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:23](I)[CH:24]=[CH2:25]>C1COCC1>[C:1]1([C@H:7]([CH2:25][CH:24]=[CH2:23])[C:8]([N:10]2[C@@H:14]([CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:13][O:12][C:11]2=[O:22])=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: C=CCI
Reactant: O=C(Cc1ccccc1)N1C(=O)OC[C@@H]1Cc1ccccc1
Solvent: C1CCOC1
Product: C=CC[C@H](C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1)c1ccccc1
Temperature: 0 °C
Reaction time: 12 h

Procedure:
To a solution of 15.5 gm of 3-phenylacetyl-4-(S)-benzyl-2-oxazolidinone (52 mmol) in 100 mL of THF at −78° C. in a nitrogen atmosphere was added dropwise 63 mL of a 1M solution of lithium bis(trimethylsilyl)azide (63 mmol). The reaction mixture was warmed to 0° C. over the period of 1 hr and then recooled to −78° C. To the reaction mixture was added 5.3 mL of allyl iodide (57 mmol). The reaction mixture was slowly warmed to room temperature and stirred for 12 hr. The reaction was quenched with saturated NH4Cl solution and the mixture was extracted with ethyl acetate. The combined organic fractions were washed with solutions of saturated NaHCO3 and NaCl, dried over MgSO4, filtered and concentrated. The residue was purified by chromatography (silica, 2:1 hexanes:ethyl acetate) to give the title compound.
Reaction SMILES: C([O:8][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:17]=1[N:16]([CH3:18])[CH:15]=[CH:14]2)C1C=CC=CC=1.[H][H]>C(O)C.[Pd]>[CH3:18][N:16]1[C:17]2[C:13](=[CH:12][CH:11]=[CH:10][C:9]=2[OH:8])[CH:14]=[CH:15]1
Reactant: Cn1ccc2cccc(OCc3ccccc3)c21
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: Cn1ccc2cccc(O)c21
Yield: 87 %

Procedure:
To a solution of 7-benzyloxy-1methyl-1H-indole in 20 mL of ethanol was added 10% palladium on charcoal (0.2 g). This solution was stirred under balloon pressure hydrogen atmosphere for 4 h, then filtered through celite and concentrated in vacuo. This material was purified by flash chromatography, eluting silica gel with hexane:ethyl acetate (100:0 to 50:50) to give the product (0.58 g, 87%); Mass spectrum (TOF): m/z=147.1 (M).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([NH2:8])[CH:5]=[N:6][CH:7]=1.N1C=CC=CC=1.[F:15][C:16]1[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[CH:18][C:17]=1[S:24](Cl)(=[O:26])=[O:25]>ClCCl>[Br:1][C:2]1[CH:3]=[C:4]([NH:8][S:24]([C:17]2[CH:18]=[CH:19][C:20]([O:22][CH3:23])=[CH:21][C:16]=2[F:15])(=[O:25])=[O:26])[CH:5]=[N:6][CH:7]=1
Reactant: Nc1cncc(Br)c1
Reactant: COc1ccc(S(=O)(=O)Cl)c(F)c1
Solvent: c1ccncc1
Solvent: ClCCl
Product: COc1ccc(S(=O)(=O)Nc2cncc(Br)c2)c(F)c1
Yield: 75.9 %

Procedure:
5-Bromopyridin-3-amine (500 mg, 2.89 mmol) was dissolved in dichloromethane (14 ml) and pyridine (4 ml) was added. To this mixture 2-fluoro-4-methoxybenzene-1-sulfonyl chloride (1 g, 4.45 mmol) was added dropwise and the mixture stirred at reflux for 5 h. Once at room temperature, the reaction mixture was washed with water and brine, dried over magnesium sulphate, filtered and the solvents were removed under reduced pressure. The product was purified by flash chromatography (0% to 50% DCM/AcOEt) to give 792 mg (76% yield) of the title compound as a white solid.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1.S(=O)(=O)(O)O.[CH3:16]O>>[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([O:8][CH3:16])=[O:7])=[CH:4][CH:3]=1
Reactant: CO
Reactant: Nc1ccc(C(=O)O)cc1
Agent: O=S(=O)(O)O
Product: COC(=O)c1ccc(N)cc1
Temperature: 25 °C
Reaction time: 6.5 h

Procedure:
To a solution of 4-amino benzoic acid (20.0 g, 0.14 mol) in methanol (400 mL) was added conc. sulphuric acid (40 mL). The reaction mass was stirred at RT for 6-7 h. The reaction mass was quenched with water and basified with NaHCO3 and extracted with DCM. The organic layer was dried over anhydrous sodium sulphate and concentrated to afford 15.0 g of the desired product. 1H NMR (300 MHz, DMSO d6): δ 3.72 (s, 3H), 5.96 (br s, 2H), 6.55 (d, J=8.1 Hz, 2H), 7.64 (d, J=8.4 Hz, 2H) MS (m/z): 152.21 (M+H)+.