Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.C([Mg]Cl)CCC.CCCCCC.C([Li])CCC.Br[C:24]1[CH:29]=[CH:28][C:27]([CH:30]=C(C)C)=[CH:26][N:25]=1.[Cl-].[NH4+]>O1CCCC1.CN(C)C=O>[CH3:26][C:27]([CH3:30])=[CH:28][C:29]1[CH:5]=[CH:4][C:3]([CH:2]=[O:1])=[N:25][CH:24]=1
Reactant: CC(C)=Cc1ccc(Br)nc1
Reactant: C1CCOC1
Agent: CCCC[Mg]Cl
Agent: [Cl-]
Agent: [Li]CCCC
Solvent: CN(C)C=O
Solvent: CCCCCC
Product: CC(C)=Cc1ccc(C=O)nc1
Temperature: -10 °C
Reaction time: 0.17 h
Yield: 83 %

Procedure:
Under a nitrogen atmosphere, a 2.0M butylmagnesium chloride tetrahydrofuran solution (11.2 mL) was diluted with tetrahydrofuran (200 mL). The reaction solution was cooled to −10° C., a 1.6M n-butyllithium hexane solution (28.1 mL) was added dropwise, and the mixture was stirred at −10° C. for 10 min. To the reaction solution was added dropwise a solution (50 mL) of 2-bromo-5-(2-methylprop-1-en-1-yl)pyridine (11.9 g) in tetrahydrofuran, and the mixture was stirred at −10° C. for 30 min. To the reaction solution was added N,N-dimethylformamide (8.65 mL), and the mixture was stirred at −10° C. for 3 hr. A saturated aqueous ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:99-10:90, volume ratio) to give the title compound (7.47 g, yield 83%) as a pale-yellow oil.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N+:4]([O-:27])[CH:5]=[C:6]([Cl:26])[C:7]=1[CH2:8][C@@H:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH:18]([F:20])[F:19])=[C:13]([O:21][CH2:22][CH:23]2[CH2:25][CH2:24]2)[CH:12]=1)[OH:10].[C:28]([O:32][C:33]([N:35]([C:40]1[CH:45]=[CH:44][C:43]([CH2:46][CH2:47][C:48](O)=[O:49])=[CH:42][CH:41]=1)[S:36]([CH3:39])(=[O:38])=[O:37])=[O:34])([CH3:31])([CH3:30])[CH3:29].C(Cl)CCl>CN(C=O)C.CN(C1C=CN=CC=1)C.O>[C:28]([O:32][C:33]([N:35]([C:40]1[CH:41]=[CH:42][C:43]([CH2:46][CH2:47][C:48]([O:10][C@H:9]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH:18]([F:20])[F:19])=[C:13]([O:21][CH2:22][CH:23]3[CH2:25][CH2:24]3)[CH:12]=2)[CH2:8][C:7]2[C:6]([Cl:26])=[CH:5][N+:4]([O-:27])=[CH:3][C:2]=2[Cl:1])=[O:49])=[CH:44][CH:45]=1)[S:36]([CH3:39])(=[O:38])=[O:37])=[O:34])([CH3:31])([CH3:30])[CH3:29]
Reactant: CC(C)(C)OC(=O)N(c1ccc(CCC(=O)O)cc1)S(C)(=O)=O
Reactant: [O-][n+]1cc(Cl)c(C[C@H](O)c2ccc(OC(F)F)c(OCC3CC3)c2)c(Cl)c1
Agent: CN(C)c1ccncc1
Solvent: CN(C)C=O
Solvent: ClCCCl
Solvent: O
Product: CC(C)(C)OC(=O)N(c1ccc(CCC(=O)O[C@@H](Cc2c(Cl)c[n+]([O-])cc2Cl)c2ccc(OC(F)F)c(OCC3CC3)c2)cc1)S(C)(=O)=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 76.6 %

Procedure:
(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (30 mg, 0.07 mmol) and 3-(4-(N-(tert-butoxycarbonyl)methylsulfonamido)phenyl)propanoic acid (48 mg, 0.14 mmol) were dissolved in DMF (2 ml), and DMAP (17 mg, 0.14 mmol) and EDC (40 mg, 0.21 mmol) were added. The mixture was stirred at RT overnight, then was diluted with water. The precipitate was filtered, dissolved in EtOAc and washed with HCl 1N and NaHCO3 sat. sol. The organic phase was dried over Na2SO4 and evaporated under vacuum to give 40 mg of crude product, that was used for the next step without any further purification.
Reaction SMILES: [C:1](Cl)(=[O:4])[CH:2]=[CH2:3].[C:6]12([NH2:16])[CH2:15][CH:10]3[CH2:11][CH:12]([CH2:14][CH:8]([CH2:9]3)[CH2:7]1)[CH2:13]2.C(N(CC)CC)C>C(OCC)C>[C:6]12([NH:16][C:1](=[O:4])[CH:2]=[CH2:3])[CH2:13][CH:12]3[CH2:11][CH:10]([CH2:9][CH:8]([CH2:14]3)[CH2:7]1)[CH2:15]2
Reactant: C=CC(=O)Cl
Reactant: NC12CC3CC(CC(C3)C1)C2
Solvent: CCOCC
Solvent: CCN(CC)CC
Product: C=CC(=O)NC12CC3CC(CC(C3)C1)C2
Temperature: 25 °C
Reaction time: 72 h

Procedure:
A solution of acryloyl chloride (4.05 ml, 0.05 mole) in ethyl ether (25 ml) was added to a cold (+5° C.) solution of 1-adamantaneamine (7.65 g, 0.05 mole) and triethylamine (15.3 ml, 0.11 mole) in ethyl ether (300 ml) and the solution stirred for 72 hours at room temperature. The solvent was removed on a rotary evaporator. The residue was dissolved in ethyl acetate (100 ml), washed with 10 percent hydrochloric acid (100 ml) and water (50 ml), dried over sodium sulfate, filtered and the solvent removed in vacuo leaving an oily solid which was crystallized from methanol-ethyl acetate-hexane. The structure was confirmed by NMR.
Reaction SMILES: Cl.[CH2:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH:3]1[NH:11][C:12]1[N:13]=[CH:14][C:15]2[CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19][CH2:18][C:16]=2[N:17]=1.COC(C)(C)C.O>O1CCCC1.C(OCC)(=O)C>[CH2:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH:3]1[NH:11][C:12]1[N:13]=[CH:14][C:15]2[CH2:21][NH:20][CH2:19][CH2:18][C:16]=2[N:17]=1
Reactant: CC(C)(C)OC(=O)N1CCc2nc(NC3Cc4ccccc4C3)ncc2C1
Agent: Cl
Solvent: COC(C)(C)C
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: c1ccc2c(c1)CC(Nc1ncc3c(n1)CCNC3)C2
Temperature: 50 °C
Reaction time: 1 h
Yield: 36.7 %

Procedure:
Add portionwise hydrochloric acid (900 mL; 5M in water; 5.17 equiv; 4.50 mole; 1.08 kg) to a solution of tert-butyl 2-(indan-2-ylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylate (319 g; 1.00 equiv; 870.48 mmoles) in tetrahydrofuran (1.5 L). Once the addition is complete, stir the solution at 50° C. for 1 h. Cool the mixture to 25° C. and then add 3 L methyltert-butyl ether and 1 L water. Allow the solution to stand at 20° C. for 16 h. Separate the phases and extract the aqueous phase with dichloromethane (2 L). Discard the organic extracts and adjust the aqueous phase to pH 10 using 4M sodium hydroxide. Extract with ethyl acetate (3×3 L), and wash the combined organic extracts with saturated sodium chloride (2 L). Dry over anhydrous sodium sulfate, filter and concentrate to dryness to give a red gel. Redissolve the substance in ethyl acetate (300 mL) and petroleum ether (200 mL) at 50° C., and allow for precipitation over 24 hours. Filter and dry to afford the title compound (85 g, 37%). MS (m/z): 267 (M+1).
Reaction SMILES: [F:1][C:2]1[CH:9]=[C:8]([F:10])[C:7]([F:11])=[CH:6][C:3]=1[C:4]#[N:5].S(=O)(=O)(O)[OH:13]>>[F:1][C:2]1[CH:9]=[C:8]([F:10])[C:7]([F:11])=[CH:6][C:3]=1[C:4]([NH2:5])=[O:13]
Reactant: O=S(=O)(O)O
Reactant: N#Cc1cc(F)c(F)cc1F
Product: NC(=O)c1cc(F)c(F)cc1F
Temperature: 0 °C

Procedure:
In 20 ml of 80% sulfuric acid was dissolved 5.8 g of 2,4,5-trifluorobenzonitrile and the mixture was heated under reflux for 30 minutes. After cooling, the reaction mixture was poured into ice-water and extracted with ethyl acetate. The extract was dried over sodium sulfate and the solvent was removed to yield 5.32 g of 2,4,5-trifluorobenzamide.
Reaction SMILES: IC.[Cl:3][C:4]1[CH:25]=[CH:24][C:7]([CH2:8][NH:9][C:10]([C:12]2[N:13]=[N:14][C:15]3[C:20]([C:21]=2[OH:22])=[CH:19][C:18]([I:23])=[CH:17][CH:16]=3)=[O:11])=[CH:6][CH:5]=1.[C:26]([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([CH2:8][NH:9][C:10]([C:12]2[C:21](=[O:22])[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([I:23])[CH:19]=3)[N:14]([CH3:26])[N:13]=2)=[O:11])=[CH:24][CH:25]=1
Reactant: O=C(NCc1ccc(Cl)cc1)c1nnc2ccc(I)cc2c1O
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Solvent: CI
Product: Cn1nc(C(=O)NCc2ccc(Cl)cc2)c(=O)c2cc(I)ccc21
Temperature: 90 °C
Yield: 39 %

Procedure:
Iodomethane (0.028 mL) is added to a suspension of N-(4-chlorobenzyl)-4-hydroxy-6-iodo-3-cinnolinecarboxamide; (Prep. 4, 0.16 g) and K2CO3 (0.20 g,) in 6 mL anhydrous DMF. The reaction is heated at 90° C. for 1 h. The reaction is cooled to room temperature and poured into 75 mL H2O. The resulting yellow solid is filtered and dried. The solid is dissolved in CH2Cl2 and adsorbed onto silica. Purification by chromatography (CH2Cl2 (2L), 0.5% MeOH/CH2Cl2 (2L), 0.75% MeOH/CH2Cl2 (1L), 1% MeOH/CH2Cl2 (1L), 1.5% MeOH/CH2Cl2 (1L), 3.5% MeOH/CH2Cl2 (1L), 10% MeOH/CH2Cl2 (1L)) affords the product as an off-white solid (0.062 g, 39%). Physical characteristics are as follows: m.p. 194-195° C.; 1H NMR (300 MHz, DMSO-d6) δ9.86, 8.52, 8.24, 7.76, 7.40, 7.38, 4.55, 4.22; IR (drift) 1671, 1601, 1589, 1549, 1544, 1490, 1463, 1412, 1320, 1278, 1180, 819, 808, 723, 666 cm−1; MS (ESI) m/z 453.7 (M+H)+, 452.8 (M−H)−; Anal. Calcd for C17H13ClIN3O2: C, 45.01; H, 2.89; N, 9.26; Found: C, 44.63; H, 2.98; N, 8.91.
Reaction SMILES: [NH2:1][C@@H:2]([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[C:9]([OH:14])[CH:8]=1)[C:3]([OH:5])=[O:4].S(=O)(=O)(O)O.[CH2:20]=O>O>[OH:14][C:9]1[CH:8]=[C:7]2[C:12](=[CH:11][C:10]=1[OH:13])[CH2:20][NH:1][C@H:2]([C:3]([OH:5])=[O:4])[CH2:6]2
Reactant: N[C@@H](Cc1ccc(O)c(O)c1)C(=O)O
Reactant: C=O
Agent: O=S(=O)(O)O
Solvent: O
Product: O=C(O)[C@@H]1Cc2cc(O)c(O)cc2CN1
Reaction time: 8 h

Procedure:
(S)-2-Amino-3-(3,4-dihydroxy-phenyl)-propionic acid (90 g) was suspended in 0.8 L water, then 18.2 mL concentrated sulfuric acid in 0.5 L additional water was added with stirring. Formaldehyde solution (136 mL, 37 wt %) was then added while stirring and the mixture was stirred 18 hours at rt. It was quenched by addition of 24.4 g NaOH in 0.5 L water, dropwise over 1 h while cooling. The resulting mixture was stored overnight at 4° C., and the solid that formed was collected by filtration, washed with hot water (70° C.), cooled again and collected by filtration. The solid was treated with 0.5 L MeOH and evaporated, then stored under vacuum overnight to give 65 g desired product. 1H NMR (400 MHz, MeOH-d4): 6.64(s, 1H), 6.59(s, 1H), 4.29-4.21(m, 3H), 3.29-3.21(m, 1H), 3.11-3.01(m, 1H).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[C:12]([CH3:19])([CH3:18])[CH2:13][C:14]([CH3:17])([CH3:16])[CH3:15])[O:8][C:7]([CH2:21][O:22][C:23]1[CH:36]=[CH:35][C:26]([CH2:27][CH:28]3[S:32][C:31](=[O:33])[NH:30][C:29]3=[O:34])=[CH:25][CH:24]=1)([CH3:20])[CH2:6][C:5]2=O.Cl.[NH2:39][OH:40].N1C=CC=CC=1>CO>[OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[C:12]([CH3:19])([CH3:18])[CH2:13][C:14]([CH3:16])([CH3:17])[CH3:15])[O:8][C:7]([CH2:21][O:22][C:23]1[CH:24]=[CH:25][C:26]([CH2:27][CH:28]3[S:32][C:31](=[O:33])[NH:30][C:29]3=[O:34])=[CH:35][CH:36]=1)([CH3:20])[CH2:6]/[C:5]/2=[N:39]\[OH:40]
Reactant: NO
Reactant: CC(C)(C)CC(C)(C)c1cc2c(cc1O)C(=O)CC(C)(COc1ccc(CC3SC(=O)NC3=O)cc1)O2
Agent: Cl
Solvent: c1ccncc1
Solvent: CO
Product: CC(C)(C)CC(C)(C)c1cc2c(cc1O)/C(=N/O)CC(C)(COc1ccc(CC3SC(=O)NC3=O)cc1)O2

Procedure:
The procedure described in Example 13 was repeated, but using 1.0 g of 5-{4-[6-hydroxy-2-methyl-4-oxo-7-(1,1,3,3-tetramethylbutyl)chroman -2-ylmethoxy]benzyl}thiazolidine-2,4-dione (prepared as described in Example 7), 0.26 g of hydroxylamine hydrochloride, 0.3 g of pyridine and 10 ml of methanol, to give the title compound as a white powder, softening at 115°-120° C.
Reaction SMILES: [Li].[F:2][CH:3]([F:22])[O:4][C:5]1[CH:6]=[C:7]([C:12]([O-])=[CH:13][C:14](=O)[C:15]([O:17]CC)=[O:16])[CH:8]=[C:9]([F:11])[CH:10]=1.ClC1C=C(C2N(C3C=CC=CN=3)N=C(C(O)=O)C=2)C=C(F)C=1.Cl.[Cl:46][C:47]1[CH:52]=[C:51]([NH:53][NH2:54])[CH:50]=[CH:49][N:48]=1>>[F:11][C:9]1[CH:8]=[C:7]([C:12]2[N:53]([C:51]3[CH:50]=[CH:49][N:48]=[C:47]([Cl:46])[CH:52]=3)[N:54]=[C:14]([C:15]([OH:17])=[O:16])[CH:13]=2)[CH:6]=[C:5]([O:4][CH:3]([F:2])[F:22])[CH:10]=1
Reactant: CCOC(=O)C(=O)C=C([O-])c1cc(F)cc(OC(F)F)c1
Reactant: NNc1ccnc(Cl)c1
Agent: Cl
Agent: O=C(O)c1cc(-c2cc(F)cc(Cl)c2)n(-c2ccccn2)n1
Agent: [Li]
Product: O=C(O)c1cc(-c2cc(F)cc(OC(F)F)c2)n(-c2ccnc(Cl)c2)n1

Procedure:
590 mg (1.01 mmol) of the compound of Example 7A is reacted analogously to the synthesis of the compound of Example 20A with 200 mg (1.11 mmol) of 2-chloropyridin-4-yl-hydrazine hydrochloride. After hydrolysis, 160 mg (41% of theory) of the title compound is obtained.
Reaction SMILES: [C:1]1([CH:7]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[O:8][C:9]2[C:14](=[O:15])[CH:13]=[C:12]([CH2:16][OH:17])O[CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:24]1[CH:28]=[C:27]([CH2:29][NH2:30])[O:26][CH:25]=1>CO.C(Cl)(Cl)Cl>[C:1]1([CH:7]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[O:8][C:9]2[C:14](=[O:15])[CH:13]=[C:12]([CH2:16][OH:17])[N:30]([CH2:29][C:27]3[O:26][CH:25]=[CH:24][CH:28]=3)[CH:10]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=c1cc(CO)occ1OC(c1ccccc1)c1ccccc1
Reactant: NCc1ccco1
Solvent: ClC(Cl)Cl
Solvent: CO
Product: O=c1cc(CO)n(Cc2ccco2)cc1OC(c1ccccc1)c1ccccc1
Reaction time: 96 h
Yield: 70.2 %

Procedure:
To a solution of 3.083 g of 3-diphenylmethoxy-6-hydroxymethyl-4-pyrone in 50 ml of methanol is added 7.645 g of 2-furfurylamine at room temperature, and the mixture is stirred for 4 days. The reaction mixture is condensed under reduced pressure, and the resulting residue is dissolved in 600 ml of chloroform. The organic solution is washed with water, a saturated aqueous potassium hydrogen sulfate solution in this sequence, dried over anhydrous magnesium sulfate and condensed under reduced pressure. The resulting crystal is collected by filtration, washed with a small amount of chloroform and dried under reduced pressure to give the title compound (2.72 g).
Reaction SMILES: [H-].[Na+].[CH3:3][CH:4]([O:7][C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=1)[CH2:5][CH3:6].S(O[CH2:20][C:21]1[O:26][C:25]2[CH:27]=[CH:28][CH:29]=[CH:30][C:24]=2[O:23][CH:22]=1)(C)(=O)=O.O>CN(C=O)C>[CH3:3][CH:4]([O:7][C:8]1[CH:9]=[CH:10][C:11]([O:14][CH2:20][C:21]2[O:26][C:25]3[CH:27]=[CH:28][CH:29]=[CH:30][C:24]=3[O:23][CH:22]=2)=[CH:12][CH:13]=1)[CH2:5][CH3:6]
Reactant: CS(=O)(=O)OCC1=COc2ccccc2O1
Reactant: CCC(C)Oc1ccc(O)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCC(C)Oc1ccc(OCC2=COc3ccccc3O2)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To sodium hydride (0.53 g, 50% in oil, 11.0 mmol) in 40 ml of DMF, under N2 at 5°, is added, dropwise and with vigorous stirring, a solution of 4-(1-methylpropoxy)phenol (1.66 g, 10.0 mmol) in 10 ml of DMF. After the mixture is stirred at RT for 1 hour, a solution of 2-mesyloxymethyl-1,4-benzodioxin (2.70 g, 11.0 mmol) in 10 ml of DMF is slowly added. The resulting reaction mixture is stirred at RT for 48 hours and is then mixed with water and extracted with ether. The combined organic extracts are washed with water and with brine, dried and solvent removed and the product is purified by column chromatography to give 2-[4-(1-methylpropoxy)phenoxymethyl]-1,4-benzodioxin, MS m/e 315 (M+).
Reaction SMILES: [CH:1]1[CH:2]=[CH:3][N:4]2[CH2:10][C:9]3[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=3[N:7]([C:15]([C:17]3[CH:22]=[CH:21][C:20](B4OC(C)(C)C(C)(C)O4)=[C:19]([CH3:32])[CH:18]=3)=[O:16])[CH2:6][C:5]=12.FC(F)(F)S(O[C:39]1[CH2:44][CH2:43][CH2:42][CH2:41][CH:40]=1)(=O)=O.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH:1]1[CH:2]=[CH:3][N:4]2[CH2:10][C:9]3[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=3[N:7]([C:15]([C:17]3[CH:22]=[CH:21][C:20]([C:39]4[CH2:44][CH2:43][CH2:42][CH2:41][CH:40]=4)=[C:19]([CH3:32])[CH:18]=3)=[O:16])[CH2:6][C:5]=12
Reactant: Cc1cc(C(=O)N2Cc3cccn3Cc3ccccc32)ccc1B1OC(C)(C)C(C)(C)O1
Reactant: O=S(=O)(OC1=CCCCC1)C(F)(F)F
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: Cc1cc(C(=O)N2Cc3cccn3Cc3ccccc32)ccc1C1=CCCCC1
Temperature: 60 °C
Yield: 0 %

Procedure:
(10,11-Dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-methanone of Step B (3.50 g, 8.17 mmol), cyclohex-1-en-1-yl trifluoromethanesulfonate (2.26 g, 9.80 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (0.200 g, 0.245 mmol) were combined in N,N-dimethylformamide (40.9 mL). Aqueous sodium carbonate (2 M, 20.5 mL, 40.9 mmol) was added and the reaction heated to 60° C. overnight. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate and the organic layer washed with water and brine. The organic phase was dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was dissolved in hot ethyl acetate/petroleum ether (1:1) and filtered. The filtrate was concentrated and the residue recrystallized from petroleum ether to afford 2.52 μg of the title compound as light brown crystals, m.p. 182-183° C.
Reaction SMILES: [NH2:1][C:2]1[N:3]=[CH:4][C:5]2[S:10][C:9](=[O:11])[NH:8][C:6]=2[N:7]=1.C(O)(=O)C.C(O)(=O)C.C(O)(=O)C.C(O)(=O)C.C(O[C@@H:32]1[O:44][C@H:43]([CH2:45][O:46][C:47](=[O:49])[CH3:48])[C@@H:38]([O:39][C:40](=[O:42])[CH3:41])[C@H:33]1[O:34][C:35](=[O:37])[CH3:36])(=O)C>>[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[S:10][C:9](=[O:11])[N:8]([C@@H:32]3[O:44][C@H:43]([CH2:45][O:46][C:47](=[O:49])[CH3:48])[C@@H:38]([O:39][C:40](=[O:42])[CH3:41])[C@H:33]3[O:34][C:35](=[O:37])[CH3:36])[C:6]=2[N:7]=1
Reactant: Nc1ncc2sc(=O)[nH]c2n1
Reactant: CC(=O)OC[C@H]1O[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H]1OC(C)=O
Solvent: CC(=O)O
Product: CC(=O)OC[C@H]1O[C@@H](n2c(=O)sc3cnc(N)nc32)[C@H](OC(C)=O)[C@@H]1OC(C)=O
Temperature: 150 °C
Yield: 39.9 %

Procedure:
Compound 86 (62 mg, 0.4 mmol), 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose tetraacetate (128 mg, 0.4 mmol), and catalytic bis(p-nitrophenyl)hydrogen phosphate (13 mg, 0.04 mmol) were mixed and placed in a 500 ml flask. The reaction vessel was carefully placed under vacuum (˜5.0 mmHg) and lowered into an oil bath heated at 150° C. for 10 minutes. After cooling to room temperature, the solids were washed with ethyl acetate. The crude product was purified by flash column. (silica, 5 to 35% ethyl acetate gradient in chloroform) to yield 68 mg of compound 79 (40%) as a white solid as a white powder identical in all respects to material isolated in Example 38, step 2.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][OH:10])=[CH:4][CH:3]=1.[Br:11][CH2:12][CH2:13][CH2:14][CH2:15]Br.[OH-].[Na+]>S(=O)(=O)(O)[O-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[Br:11][CH2:12][CH2:13][CH2:14][CH2:15][O:10][CH2:9][CH2:8][C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1
Reactant: OCCc1ccc(F)cc1
Reactant: BrCCCCBr
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=S(=O)([O-])O
Agent: [Na+]
Solvent: O
Product: Fc1ccc(CCOCCCCBr)cc1
Temperature: 25 °C
Reaction time: 20 h
Yield: 88.1 %

Procedure:
A mixture of 4-fluorobenzeneethanol (10.0 g), 1,4-dibromobutane (59.0 g), aqueous sodium hydroxide (50% w/v; 40 ml) and tetrabutylammonium bisulphate (1 g) was stirred at room temperature for 20 h, diluted with water (50 ml) and extracted with ER (2×100 ml). The dried extract was evaporated and the residue was purified by [C] eluting with cyclohexane followed by cyclohexane-ER (19:1) to give the title compound as a colourless oil (17.3 g). T.l.c. (cyclohexane-ER 9:1) Rf 0.4
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:9]2[CH:24]=[CH:23][C:12]([C:13]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([Br:22])=[CH:18][CH:17]=3)=[O:14])=[CH:11][C:10]=2[NH:25][C:26]2[C:27]3[CH:35]=[CH:34][C:33]([CH:36]([CH3:38])[CH3:37])=[N:32][C:28]=3[N:29]=[CH:30][N:31]=2)=[CH:4][CH:3]=1.[NH:39](C(OC(C)(C)C)=O)[C@H:40]([C:43](O)=[O:44])[CH2:41][CH3:42].C(OP(ON1C(=O)C2C=CC=CC=2N=N1)(OCC)=O)C.C(N(CC)CC)C.C(=O)([O-])[O-].[Na+].[Na+]>>[NH2:39][CH:40]([CH2:41][CH3:42])[C:43]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:9]2[CH:24]=[CH:23][C:12]([C:13]([NH:15][C:16]3[CH:17]=[CH:18][C:19]([Br:22])=[CH:20][CH:21]=3)=[O:14])=[CH:11][C:10]=2[NH:25][C:26]2[C:27]3[CH:35]=[CH:34][C:33]([CH:36]([CH3:38])[CH3:37])=[N:32][C:28]=3[N:29]=[CH:30][N:31]=2)=[CH:4][CH:3]=1)=[O:44]
Reactant: CC(C)c1ccc2c(Nc3cc(C(=O)Nc4ccc(Br)cc4)ccc3Sc3ccc(N)cc3)ncnc2n1
Reactant: CC[C@H](NC(=O)OC(C)(C)C)C(=O)O
Agent: CCOP(=O)(OCC)On1nnc2ccccc2c1=O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCN(CC)CC
Product: CCC(N)C(=O)Nc1ccc(Sc2ccc(C(=O)Nc3ccc(Br)cc3)cc2Nc2ncnc3nc(C(C)C)ccc23)cc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of the product from Example 13E (59 mg, 0.1 mmol) and Boc-Abu-OH (22 mg, 0.11 mmol) in tetrohydrofuran (5 ml) was added 3-(diethoxyphosphoryloxy)-1,2,3-benzo-triazin-4(3H)-one (36 mg, 0.11 mmol) and triethylamine (0.07 ml, 0.5 mmol). The mixture was stirred at room temperature for 16 hours then poured into saturated sodium carbonate solution and extracted with ethyl acetate. The organic layer was dried with magnesium sulfate, filtered and evaporated. To the residue was added dichloromethane (2 ml) and trifluoroacetic acid (2 ml) then stirred at room temperature for 1 hour. The solvent was evaporated and the residue was purified by HPLC with NH4OH to provide the title compound. (62 mg, 85%). 1H NMR (300 MHz, DMSO-D6) δ ppm: 0.90 (t, J=7.54 Hz, 3 H) 1.33 (d, J=6.99 Hz, 6 H) 1.48 (m, 1 H) 1.66 (m, 1 H) 1.90 (s, 3 H) 3.22 (m, 2 H) 7.02 (m, 2 H) 7.40 (d, J=8.46 Hz, 2 H) 7.52 (d, J=8.46 Hz, 2 H) 7.61 (d, J=8.46 Hz, 1 H) 7.72 (m, 5 H) 7.94 (s, 1 H) 8.52 (s, 1 H) 8.79 (s, 1 H) 10.33 (s, 1 H); MS (ESI+) m/z 670, 672 (M+H)+.
Reaction SMILES: C([Li])CCC.Cl[C:7]1[S:8][CH:9]=[CH:10][N:11]=1.[CH2:12]([N:15]=[C:16]=[O:17])[CH2:13][CH3:14].O>CCCCCC.O1CCCC1>[CH2:12]([NH:15][C:16]([C:9]1[S:8][CH:7]=[N:11][CH:10]=1)=[O:17])[CH2:13][CH3:14]
Reactant: Clc1nccs1
Reactant: CCCN=C=O
Agent: [Li]CCCC
Solvent: O
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CCCNC(=O)c1cncs1
Temperature: 100 °C
Reaction time: 0.17 h
Yield: 68.9 %

Procedure:
Butyl lithium (2.4 M, 50 ml) in hexane was added to a solution of 2-chlorothiazole (12.43 g, 0.104 mol) in tetrahydrofuran (400 ml) at -78° C. under at atmosphere of nitrogen. The resultant solution was stirred for 5 minutes before propyl isocyanate (11.25 ml, 0.12 mol) was added and the reaction mixture was then stirred for a further 10 minutes before being hydrolysed with water (100 ml). The solvent was removed under reduced pressure and the residue extracted with ethyl acetate (2×400 ml). The combined organic extract was then washed with saturated sodium chloride solution, dried over magnesium sulphate and the solvent evaporated. Acetic acid (110 ml) was added to the residue and the solution warmed to about 100° C. whereupon zinc dust (11.8 g) was added and the mixture was refluxed for 1 hour. On cooling, the reaction mixture was made basic with ammonium hydroxide and then extracted into ethyl acetate (4×250 ml). The combined organic extract was washed with saturated sodium chloride solution, dried (MgSO4) and then concentrated. Flash chromatography of the residue on a silica gel column using ethyl acetate as eluant gave N-propylthiazole-5-carboxamide (12.2 g) as a pale yellow solid, m.pt. 86° C.
Reaction SMILES: C([O:4][CH:5]1[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][C:11]=2[N:14]2[CH:18]=[CH:17][CH:16]=[CH:15]2)[CH2:6]1)(=O)C.[OH-].[K+]>O.C(O)C>[N:14]1([C:11]2[CH:10]=[CH:9][CH:8]=[C:7]3[C:12]=2[CH2:13][CH:5]([OH:4])[CH2:6]3)[CH:15]=[CH:16][CH:17]=[CH:18]1
Reactant: CC(=O)OC1Cc2cccc(-n3cccc3)c2C1
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: OC1Cc2cccc(-n3cccc3)c2C1
Yield: 52.7 %

Procedure:
In the manner of Example 1, step H, hydrolysis of 0.84 g (0.004 mole) of 4-(1-pyrrolyl)-2-indanyl acetate with 0.28 g (0.005 mole) of potassium hydroxide in 5 mL of water and 10 mL of ethanol gave 0.42 g of 4-(1-pyrrolyl)-2-indanol.