Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]([C:12]#[N:13])[CH:9]=[C:8]([F:14])[C:3]=1[C:4]([O:6]C)=[O:5].[I-].[Li+]>N1C=CC=CC=1>[Cl:1][C:2]1[CH:11]=[C:10]([C:12]#[N:13])[CH:9]=[C:8]([F:14])[C:3]=1[C:4]([OH:6])=[O:5]
Reactant: COC(=O)c1c(F)cc(C#N)cc1Cl
Agent: [I-]
Agent: [Li+]
Solvent: c1ccncc1
Product: N#Cc1cc(F)c(C(=O)O)c(Cl)c1
Temperature: 115 °C
Yield: 88.6 %

Procedure:
To a solution of methyl 2-chloro-4-cyano-6-fluorobenzoate (1.953 g, 9.143 mmoles) in pyridine (50 mL) was added lithium iodide (2.45 g, 18.3 mmoles). The reaction mixture was heated at 115° C. for 3 hours. The reaction was concentrated under reduced pressure and the resulting solid was triturated with EtOAc. The solid was dissolved in water and acidified to pH 4 with 1 N HCl. The aqueous solution was extracted with EtOAc (3×30 mL). The combined organic extracts were dried with Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel chromatography [0-20% (10% formic acid in MeOH)/DCM] to afford 2-chloro-4-cyano-6-fluorobenzoic acid as a white solid (1.616 g, yield: 89%). 1H NMR (400 MHz, CDCl3) δ 7.58 (s, 1H), 7.40 (dd, J=8.1, 1.0 Hz, 1H). LCMS (APCI+) [M+H]+ 200.0.
Reaction SMILES: I[C:2]1[N:3]=[C:4]([NH2:20])[C:5]2[N:6]=[CH:7][N:8]([C:18]=2[N:19]=1)[C@@H:9]1[O:17][C@H:14]([CH2:15][OH:16])[C@@H:12]([OH:13])[C@H:10]1[OH:11].[F:21][C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[C:26]([F:28])[CH:27]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:20][C:4]1[N:3]=[C:2]([C:24]2[CH:23]=[C:22]([F:21])[CH:27]=[C:26]([F:28])[CH:25]=2)[N:19]=[C:18]2[C:5]=1[N:6]=[CH:7][N:8]2[C@H:9]1[C@H:10]([OH:11])[C@H:12]([OH:13])[C@@H:14]([CH2:15][OH:16])[O:17]1
Reactant: OB(O)c1cc(F)cc(F)c1
Reactant: Nc1nc(I)nc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: Cc1ccccc1
Solvent: CCO
Product: Nc1nc(-c2cc(F)cc(F)c2)nc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
Yield: 8.7 %

Procedure:
A solution of 2-iodo adenosine (200 mg, 0.51 mmol), 3,5-difluorophenylboronic acid (150 mg, 0.95 mmol), cesium carbonate (364 mg, 1.12 mmol) and Pd(PPh3)4 (59 mg, 0.051 mmol) in toluene (1.2 mL) and ethanol (2.4 mL) was heated in a Biotage microwave (120° C., absorption high, pre-stirring 15 s) for 40 min. The solvents were then removed in vacuo and the residue dissolved in EtOAc (20 mL) and washed with sat. aq. NaHCO3 (20 mL×2) and brine (20 mL) and dried over MgSO4. Purification by reverse phase prep HPLC in 2 batches (Phenomenex Synergi, RP-Hydro 150×10 mm, 10%, 20 mL per min, gradient 5-100% acetonitrile in water over 10 min, product eluted in 35% acetonitrile) and (Phenomenex Synergi, RP-Hydro 150×10 mm, 10μ, 20 mL per min, gradient 5-100% acetonitrile in water over 10 min, product eluted in 40% acetonitrile), combination of the purer fractions from both columns, concentration in vacuo to ˜20 mL and filtration of the resulting white precipitate gave (2R,3R,4S,5R)-2-{6-amino-2-(3,5-difluorophenyl)-9H-purin-9-yl}-5-(hydroxymethyl)tetrahydrofuran-3,4-diol 10 as a white solid (16.8 mg, 9%).
Reaction SMILES: [Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7]3([CH2:27][CH2:26][CH:25]([O:28][CH3:29])[CH2:24][CH2:23]3)[C:8]2([NH:16][S:17]([C:19]([CH3:22])([CH3:21])[CH3:20])=[O:18])[C:11]([O:13][CH2:14][CH3:15])=C)=[CH:4][CH:3]=1.C[O:31]C1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=S)=CC=1>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7]3([CH2:27][CH2:26][CH:25]([O:28][CH3:29])[CH2:24][CH2:23]3)[C:8]2([NH:16][S:17]([C:19]([CH3:21])([CH3:22])[CH3:20])=[O:18])[C:11]([O:13][CH2:14][CH3:15])=[O:31])=[CH:4][CH:3]=1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: C=C(OCC)C1(NS(=O)C(C)(C)C)c2cc(Br)ccc2CC12CCC(OC)CC2
Solvent: Cc1ccccc1
Product: CCOC(=O)C1(NS(=O)C(C)(C)C)c2cc(Br)ccc2CC12CCC(OC)CC2
Yield: 22.8 %

Procedure:
A 8 mL vial was charged with compound 5 (130 mg, 0.316 mmol) and Lawesson's reagent (138 mg, 0.342 mmol). Toluene (2 mL) was added, and the vial was sealed and placed into CEM microwave reactor and irradiated at 140° C. for 1 h. After cooling down, the solvent was removed by evaporation in vacuo and the resulting residue was purified by column chromatography over silica gel (petroleum ether:EtOAc, 50:1 to 10:1) to give compound 6 (35 mg, 25%) as a whit solid. LC-MS tR=1.244 min in 2 min chromatography, MS (ESI) m/z=435.2 [M+H]+.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][N:12]([CH2:15][C:16]([O:18]CC)=[O:17])[C:11](=[O:21])[CH2:10]2)=[CH:5][CH:4]=1)#[N:2].O1CCCC1.O.O.[OH-].[Li+]>CO>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([N:9]2[CH2:14][CH2:13][N:12]([CH2:15][C:16]([OH:18])=[O:17])[C:11](=[O:21])[CH2:10]2)=[CH:7][CH:8]=1)#[N:2]
Reactant: CCOC(=O)CN1CCN(c2ccc(C#N)cc2)CC1=O
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: N#Cc1ccc(N2CCN(CC(=O)O)C(=O)C2)cc1
Reaction time: 0.33 h
Yield: 99.1 %

Procedure:
Ethyl 2-[4-(4-cyanophenyl)-2-oxopiperazino]-acetate (20.7 g, 72 mmol) is dissolved in 80 ml of methanol, 80 ml of tetrahydrofuran and 100 ml of water, and lithium hydroxide monohydrate (4 g, 98 mmol) is then added. Stirring is continued for 20 minutes and the organic solvent is then removed under vacuum. About 100 ml of water are added to the suspension obtained and this mixture is acidified. The product is filtered off, rinsed with water and dried under vacuum at 50° C. to give 18.5 g of a beige-coloured powder.
Reaction SMILES: [OH:1][C:2]1[C:3]2[C:4]3[C:5]([C:24](=[O:34])[N:25]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=4[CH3:33])[N:26]=3)=[CH:6][N:7]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([N:19]4[CH:23]=[CH:22][CH:21]=[N:20]4)=[CH:15][CH:14]=3)[C:8]=2[CH:9]=[CH:10][CH:11]=1.C(N(CC)C(C)C)(C)C.[C:44](Cl)(=[O:46])[CH3:45].C(=O)(O)[O-].[Na+]>ClCCl.CN(C1C=CN=CC=1)C>[C:44]([O:1][C:2]1[C:3]2[C:4]3[C:5]([C:24](=[O:34])[N:25]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=4[CH3:33])[N:26]=3)=[CH:6][N:7]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([N:19]4[CH:23]=[CH:22][CH:21]=[N:20]4)=[CH:15][CH:14]=3)[C:8]=2[CH:9]=[CH:10][CH:11]=1)(=[O:46])[CH3:45]
Reactant: CC(=O)Cl
Reactant: Cc1ccccc1-n1nc2c3c(O)cccc3n(Cc3ccc(-n4cccn4)cc3)cc-2c1=O
Agent: CN(C)c1ccncc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(=O)Oc1cccc2c1c1nn(-c3ccccc3C)c(=O)c-1cn2Cc1ccc(-n2cccn2)cc1
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
9-Hydroxy-2-(2-methylphenyl)-5-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (Example 724, 56 mg, 0.12 mmol) was dissolved in dichloromethane (2.5 mL), treated with N,N-dimethyl-4-aminopyridine (1.5 mg, 0.013 mmol, 0.1 equiv) and N,N-diisopropylethylamine (0.033 mL, 0.19 mmol, 1.5 equiv) and cooled to 0° C. To the mixture was added acetyl chloride (0.012 mL, 0.17 mmol, 1.4 equiv), and after 15 minutes the mixture was warmed to ambient temperature. After 15 minutes at ambient temperature, the mixture was poured into sodium bicarbonate (5 mL, aqueous saturated) and extracted with dichloromethane (2×15 mL). The combined organic extracts were washed with hydrochloric acid (2×15 mL, 1 N aqueous) and brine (1×10 mL), dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate containing 5% methanol), providing the titled compound: 1H-NMR (400 MHz, CDCl3) δ 8.47 (1H, s), 7.91 (1H, d, J=2.6 Hz), 7.73 (1H, d, J=1.7 Hz), 7.72 (2H, d, J=8.6 Hz), 7.47 (1H, t, J=8.2 Hz), 7.44-7.42 (1H, m), 7.34-7.26 (6H, m), 7.17 (1H, d, J=7.9 Hz), 6.47 (1H, dd, J=2.3, 1.9 Hz), 5.45 (2H, s), 2.33 (3H, s), 2.32 (3H, s) ppm; high resolution mass spectrometry (ES+) m/z 490.1900 [(M+H)+; calculated for C29H24N5O3: 490.1874].
Reaction SMILES: [CH2:1]([N:8]1[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][C:14]=2[C:17](OC)=[O:18])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].S([O-])([O-])(=O)=O.[Na+].[Na+]>O1CCCC1>[CH2:1]([N:8]1[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][C:14]=2[CH2:17][OH:18])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COC(=O)c1cccc2c1CN(Cc1ccccc1)C2
Agent: O=S(=O)([O-])[O-]
Agent: [Al+3]
Agent: [H-]
Solvent: C1CCOC1
Product: OCc1cccc2c1CN(Cc1ccccc1)C2
Temperature: 25 °C
Reaction time: 20 h
Yield: 73.4 %

Procedure:
8.02 g of 2-benzyl-4-methoxycarbonylisoindoline was dissolved in 20 ml of anhydrous tetrahydrofuran and to the solution was added 1.9 g of lithium aluminum hydride. After stirring for 20 hours at room temperature, an aqueous solution of sodium sulfate was added. Insoluble materials were removed by filtration, the filtrate was concentrated, and the residue was recrystallized from ether to give 5.27 g of 2-benzyl-4-hydroxymethylisoindoline.
Reaction SMILES: [NH2:1][C:2]1[N:11]=[C:10]([O:12][CH3:13])[C:9]2[C:4](=[N:5][CH:6]=[CH:7][N:8]=2)[N:3]=1.[Cl:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[S:21]([N:24]=[C:25]=[O:26])(=[O:23])=[O:22].C(OC(C)C)(C)C>C(N(CC)CC)C.C(#N)C>[CH3:13][O:12][C:10]1[C:9]2[C:4](=[N:5][CH:6]=[CH:7][N:8]=2)[N:3]=[C:2]([NH:1][C:25]([NH:24][S:21]([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[Cl:14])(=[O:22])=[O:23])=[O:26])[N:11]=1
Reactant: O=C=NS(=O)(=O)c1ccccc1Cl
Reactant: COc1nc(N)nc2nccnc12
Solvent: CCN(CC)CC
Solvent: CC(C)OC(C)C
Solvent: CC#N
Product: COc1nc(NC(=O)NS(=O)(=O)c2ccccc2Cl)nc2nccnc12
Reaction time: 0.17 h
Yield: 82.6 %

Procedure:
1.5 g (0.0069 mol) of 2-amino-4-methoxypteridine and two drops of triethylamine were added to a mixture of 1.77 g (0.01 mol) of 2-chlorophenylsulfonyl isocyanate in 20 ml of acetonitrile and the mixture was refluxed for 30 minutes, cooled and mixed with diisopropyl ether. After standing for 10 minutes, the mixture was vacuum filtered to obtain 2.25 g (87% of theory) of N-(4-methoxypteridin-2-yl)-N'-(2-chlorophenylsulfonyl)-urea melting at 212° C.
Reaction SMILES: [OH:1][C:2]1[N:6]([C:7]2[CH:12]=[C:11]([C:13]#[N:14])[CH:10]=[CH:9][N:8]=2)[N:5]=[CH:4][CH:3]=1.[F:15][C:16]1([F:22])[CH2:19][CH:18]([CH2:20]O)[CH2:17]1>>[F:15][C:16]1([F:22])[CH2:19][CH:18]([CH2:20][O:1][C:2]2[N:6]([C:7]3[CH:12]=[C:11]([C:13]#[N:14])[CH:10]=[CH:9][N:8]=3)[N:5]=[CH:4][CH:3]=2)[CH2:17]1
Reactant: OCC1CC(F)(F)C1
Reactant: N#Cc1ccnc(-n2nccc2O)c1
Product: N#Cc1ccnc(-n2nccc2OCC2CC(F)(F)C2)c1

Procedure:
The title compound was prepared from 2-(5-hydroxy-1H-pyrazol-1-yl)pyridine-4-carbonitrile and (3,3-difluorocyclobutyl)methanol according to the procedure for the preparation of Example 39, part C. 1H NMR (400 MHz, CDCl3): δ 2.48-2.71 (5H, m), 5.14 (2H, d, J=4.4 Hz), 5.64 (1H, d, J=1.6 Hz), 7.34 (1H, dd, J=0.4 Hz, J=4.8 Hz), 7.51 (1H, d, J=2.0 Hz), 7.93 (1H, s), 8.61 (1H, d, J=4.8 Hz). [M+H] Calc'd for C14H12F2N4O, 291; Found, 291.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:13]([OH:15])=O)[C:5]2[O:9][C:8]([CH3:11])([CH3:10])[CH2:7][C:6]=2[CH:12]=1.FC1C(F)=C(C(O)=O)C2OC(C)(C)CC=2C=1.[NH2:32][C:33]1[CH:38]=[CH:37][C:36]([CH2:39][CH:40]([CH3:46])[C:41]([O:43][CH2:44][CH3:45])=[O:42])=[CH:35][CH:34]=1.C(N(CC)CC)C.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>ClCCl>[F:1][C:2]1[CH:3]=[C:4]([C:13]([NH:32][C:33]2[CH:34]=[CH:35][C:36]([CH2:39][CH:40]([CH3:46])[C:41]([O:43][CH2:44][CH3:45])=[O:42])=[CH:37][CH:38]=2)=[O:15])[C:5]2[O:9][C:8]([CH3:10])([CH3:11])[CH2:7][C:6]=2[CH:12]=1
Reactant: CC1(C)Cc2cc(F)cc(C(=O)O)c2O1
Reactant: CCOC(=O)C(C)Cc1ccc(N)cc1
Agent: CC1(C)Cc2cc(F)c(F)c(C(=O)O)c2O1
Agent: CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCOC(=O)C(C)Cc1ccc(NC(=O)c2cc(F)cc3c2OC(C)(C)C3)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
5-fluoro-2,2-dimethyl-2,3-dihydrobenzofuran-7-carboxylic acid (803) (Compound was prepared in a similar manner as that described for the synthesis of (735) (101.3 mg, 0.482 mmol) was dissolved in dichloromethane (4 mL) and ethyl 3-(4-aminophenyl)-2-methylpropanoate (646) (100 mg, 0.482 mmol), triethyl amine (0.4 mL, 2.89 mmol), and 1-propanephosphonic acid cyclic anhydride (0.34 mL, 0.58 mmol, 50% in ethyl acetate) were added and stirred overnight at room temperature. The reaction was purified in vacuo and purified by flash column chromatography on silica gel with hexanes and EtOAc to give ethyl 3-(4-(5-fluoro-2,2-dimethyl-2,3-dihydrobenzofuran-7-carboxamido)phenyl)-2-methylpropanoate. The ester was dissolved in tetrahydrofuran (1.0 mL), methanol (1.0 mL) and water (3 mL). Lithium hydroxide was added and the reaction was stirred at room temperature for 4 h. The mixture was acidified with 1M HCl and diluted with EtOAc (3 mL). The organic layer was washed with brine (3 mL), dried over sodium sulfate and filtered. The filtrate was concentrated in vacuo to yield 3-(4-(5-fluoro-2,2-dimethyl-2,3-dihydrobenzofuran-7-carboxamido)phenyl)-2-methylpropanoic acid (97). 1H NMR (400 MHz, CDCl3) δ 9.53 (br, 1H), 7.66 (dd, J=9.9, 2.6 Hz, 1H), 7.57 (d, J=8.4 Hz, 2H), 7.19 (d, J=8.4 Hz, 2H), 7.02 (dd, J=9.9, 2.6 Hz, 1H), 3.13-3.00 (m, 3H), 2.72 (m, 2H), 1.60 (s, 6H), 1.19 (d, J=8.0 Hz, 3H).
Reaction SMILES: [CH2:1]([NH:19][CH:20]1[O:28][C@H:27]([CH2:29][OH:30])[C@@H:25]([OH:26])[C@H:23]([OH:24])[C@H:21]1[OH:22])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[CH2:31]([N:43]=[C:44]=[O:45])[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42]>O1CCCC1.C(O)C>[CH2:1]([N:19]([CH:20]1[O:28][C@H:27]([CH2:29][OH:30])[C@@H:25]([OH:26])[C@H:23]([OH:24])[C@H:21]1[OH:22])[C:44]([NH:43][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])=[O:45])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: CCCCCCCCCCCCCCCCCCNC1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O
Reactant: CCCCCCCCCCCCN=C=O
Solvent: CCO
Solvent: C1CCOC1
Product: CCCCCCCCCCCCCCCCCCN(C(=O)NCCCCCCCCCCCC)C1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O

Procedure:
9 g of the compound from Example 1 are suspended in 160 ml of tetrahydrofuran and 40 ml of ethanol. 4.3 g of dodecyl isocyanate, dissolved in 20 ml of tetrahydrofuran, are added dropwise to this suspension in the course of 20 minutes. When the reaction has ended, the mixture is evaporated in vacuo and the resulting syrup is purified by column chromatography (mobile phase methylene chloride/methanol, 15:1)
Reaction SMILES: Br[C:2]1[N:7]=[C:6]([O:8][CH3:9])[C:5]([NH2:10])=[CH:4][CH:3]=1.[CH3:11][N:12]1[CH:16]=[CH:15][N:14]=[C:13]1[CH3:17].CC([O-])=O.[K+]>CC(N(C)C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:11][N:12]1[C:16]([C:2]2[N:7]=[C:6]([O:8][CH3:9])[C:5]([NH2:10])=[CH:4][CH:3]=2)=[CH:15][N:14]=[C:13]1[CH3:17]
Reactant: Cc1nccn1C
Reactant: COc1nc(Br)ccc1N
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Product: COc1nc(-c2cnc(C)n2C)ccc1N
Reaction time: 8 h
Yield: 16.5 %

Procedure:
A suspension of 6-bromo-2-methoxypyridin-3-amine (96 mg, 0.473 mmol), 1,2-dimethyl-1H-imidazole (91 mg, 0.946 mmol), Pd(OAc)2 (4.3 mg, 0.019 mmol), KOAc (93 mg, 0.95 mmol) in DMA (3 mL) was stirred at 1500 under microwave irradiation for 8 hours. The reaction mixture was filtered, diluted with NaCl solution and extracted with EtOAc. The organic layer was purified by eluting through an SCX-2 column using 2M NH3/MeOH followed by Biotage silica gel column chromatography eluting with 0-4% MeOH/EtOAc to give the title compound as pink solid (17 mg, 16%).
Reaction SMILES: I([O-])(=O)(=O)=[O:2].[Na+].[Cl:7][C:8]1[N:13]=[C:12]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][C@H:15]2[CH3:20])[CH:11]=[C:10]([CH2:21][S:22][CH3:23])[N:9]=1>O.CCOC(C)=O.CO.C(Cl)Cl>[Cl:7][C:8]1[N:13]=[C:12]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][C@H:15]2[CH3:20])[CH:11]=[C:10]([CH2:21][S:22]([CH3:23])=[O:2])[N:9]=1
Reactant: [O-][I+3]([O-])([O-])[O-]
Reactant: CSCc1cc(N2CCOC[C@H]2C)nc(Cl)n1
Agent: [Na+]
Solvent: CO
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: C[C@@H]1COCCN1c1cc(CS(C)=O)nc(Cl)n1
Temperature: 20 °C
Reaction time: 16 h
Yield: 69.8 %

Procedure:
Sodium meta-periodate (2.87 g, 13.44 mmol) was added in one portion to (R)-4-(2-chloro-6-(methylthiomethyl)pyrimidin-4-yl)-3-methylmorpholine (3.68 g, 13.44 mmol) in water (10.00 ml), EtOAc (20 ml) and MeOH (10.00 ml). The resulting solution was stirred at 20° C. for 16 hours. The reaction mixture was diluted with DCM (60 ml) and then filtered. The DCM layer was separated and the aqueous layer washed with DCM (3×40 ml). The organics were combined, dried over MgSO4, filtered and then evaporated. The residue was purified by flash chromatography on silica, eluting with a gradient of 0 to 7% MeOH in DCM. Pure fractions were evaporated to afford (R)-4-(2-chloro-6-(methylsulfinylmethyl)pyrimidin-4-yl)-3-methylmorpholine (2.72 g, 70%); 1H NMR (400 MHz, DMSO-d6) 1.22 (3H, d), 2.64 (3H, d), 3.14-3.26 (1H, m), 3.45 (1H, td), 3.59 (1H, dd), 3.73 (1H, d), 3.88-3.96 (2H, m), 4.00 (1H, d), 4.07 (1H, dt), 4.33 (1H, s), 6.81 (1H, s); m/z: (ESI+) MH30, 290.43.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:22]=[CH:21][C:6]([O:7][CH2:8][C:9]2[N:10]=[C:11]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[O:12][C:13]=2[CH3:14])=[CH:5][CH:4]=1.[OH:23][C:24]1[CH:25]=[C:26]([CH2:30][CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:27]=[CH:28][CH:29]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[CH3:14][C:13]1[O:12][C:11]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[N:10][C:9]=1[CH2:8][O:7][C:6]1[CH:21]=[CH:22][C:3]([CH2:2][O:23][C:24]2[CH:25]=[C:26]([CH2:30][CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:27]=[CH:28][CH:29]=2)=[CH:4][CH:5]=1
Reactant: CCOC(=O)CCc1cccc(O)c1
Reactant: Cc1oc(-c2ccccc2)nc1COc1ccc(CCl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)CCc1cccc(OCc2ccc(OCc3nc(-c4ccccc4)oc3C)cc2)c1
Temperature: 90 °C
Reaction time: 15 h
Yield: 55.5 %

Procedure:
A mixture of 4-(4-chloromethylphenoxymethyl)-5-methyl-2-phenyloxazole (2.42 g), ethyl 3-(3-hydroxyphenyl)propionate (1.35 g), anhydrous potassium carbonate (0.97 g) and N,N-dimethylformamide (30 mL) was stirred at 90° C. for 15 hrs. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The obtained residue was subjected to silica gel column chromatography to give crystals (1.82 g, 55%) of ethyl 3-[3-[4-[(5-methyl-2-phenyl-4-oxazolyl)methoxy]benzyloxy]phenyl]propionate from a fraction eluted with ethyl acetate-hexane (1:6, v/v). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 90-91° C.
Reaction SMILES: [C:1]([C:3]1[CH:16]=[CH:15][C:6]([O:7][CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:5][CH:4]=1)#[N:2].[OH:17]O.[OH-].[Na+]>C(O)C>[NH2:2][C:1]([C:3]1[CH:16]=[CH:15][C:6]([O:7][CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:5][CH:4]=1)=[O:17]
Reactant: OO
Reactant: N#Cc1ccc(OCc2ccccc2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: NC(=O)c1ccc(OCc2ccccc2)cc1

Procedure:
A mixture of 4-cyanophenoxy phenyl methane (10.45g.; 0.05 mole), 30% hydrogen peroxide (20ml) and 6N NaOH (20ml) and ethanol (30ml) was maintained at 40°-50° for 3 hrs., cooled and neutralised. The product was filtered off and recrystallised from ethanol M.p. 186°-7°.
Reaction SMILES: [H-].[H-].[H-].[H-].[Li+].[Al+3].C([O:9][C:10](=O)[CH2:11][C:12]1[C:16]2[CH:17]=[CH:18][C:19]([Cl:21])=[CH:20][C:15]=2[O:14][CH:13]=1)C>C1COCC1>[Cl:21][C:19]1[CH:18]=[CH:17][C:16]2[C:12]([CH2:11][CH2:10][OH:9])=[CH:13][O:14][C:15]=2[CH:20]=1
Reactant: CCOC(=O)Cc1coc2cc(Cl)ccc12
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: OCCc1coc2cc(Cl)ccc12
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a stirred suspension of LiAlH4 (200 mg, excess) in THF at 0° C., ethyl(6-chloro-1-benzofuran-3-yl)acetate (1.19 g, 50 mmol) in THF (20 mL) was added slowly. After the addition, the reaction mixture was stirred at room temperature for 1 hr and quenched with saturated NH4Cl solution. The product was extracted with chloroform and washed well with water. It was dried over anhydrous MgSO4; filtered and concentrated. The product, 2-(6-chloro-1-benzofuran-3-yl)ethanol, was obtained as a white oil pure enough to be taken to the next step without purification. Yield: 900 mg (91%); 197 (M+H).
Reaction SMILES: [I:1][C:2]1[CH:3]=[N:4][NH:5][CH:6]=1.C([O-])([O-])=O.[Cs+].[Cs+].CN(C=O)C.Cl[CH2:19][CH2:20][C:21]([O:23][CH3:24])=[O:22]>CCOC(C)=O>[CH3:24][O:23][C:21](=[O:22])[CH2:20][CH2:19][N:4]1[CH:3]=[C:2]([I:1])[CH:6]=[N:5]1
Reactant: COC(=O)CCCl
Reactant: Ic1cn[nH]c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COC(=O)CCn1cc(I)cn1
Temperature: 50 °C

Procedure:
To a mixture of 4-iodopyrazole (1.000 g, 5.155 mmol), Cs2CO3 (2.016 g, 6.186 mmol), and DMF (20 mL, 0.2 mol) was added methyl 3-chloropropanoate (758.1 mg, 6.186 mmol) at 0° C. The reaction was heated to 50° C. for 1 h. The material was transferred to a separatory funnel, diluted with EtOAc, and washed with water several times to remove DMF. The organic layer was dry-loaded onto silica gel, and column chromatography was used for purification, eluting with 3:1 Hexanes/EtOAc, affording the title compound as a clear liquid. MS (ES+): m/z=280.95 (100) [MH+]. HPLC: tR=2.91 min (ZQ3, polar—5 min).
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[OH:7][C:8]1[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][CH:9]=1.[CH:18]1([CH2:21]Br)[CH2:20][CH2:19]1>[I-].[K+].CC(=O)CC>[CH:18]1([CH2:21][O:7][C:8]2[CH:9]=[CH:10][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:16][CH:17]=2)[CH2:20][CH2:19]1
Reactant: BrCC1CC1
Reactant: COC(=O)c1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CCC(C)=O
Product: COC(=O)c1ccc(OCC2CC2)cc1
Temperature: 75 °C
Reaction time: 4 h
Yield: 100.6 %

Procedure:
Potassium carbonate (114 g, 827 mmol) and potassium iodide (0.5 g) were added to a 2-butanone (535 mL) solution of methyl 4-hydroxybenzoate (52.4 g, 345 mmol) and cyclopropylmethyl bromide (72.7 g, 517 mmol) at room temperature. The mixture was stirred at 75° C. for 4 hours. The reaction solution was cooled to room temperature, and insoluble substances were separated by filtration. The insoluble substances were further washed with 2-butanone, and the filtrate was concentrated. The residue was dissolved in ethyl acetate (1 L), washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the obtained residue was dried under reduced pressure to give 71.6 g of methyl 4-(cyclopropylmethoxy)benzoate (colorless crystal). All this crystal was dissolved in methanol (715 mL), and a 2 N sodium hydroxide aqueous solution (345 mL, 690 mmol) was added thereto. The resulting mixture was stirred at 60° C. for 3 hours, and the solvents (mainly methanol) were evaporated. The residue was suspended in water (500 mL), and 2 N hydrochloric acid (360 mL) was added thereto under ice-cooling with stirring. The precipitated white solid was collected by filtration, washed with water and n-hexane, and dried under reduced pressure to give 64.6 g of the title compound (white powder, yield: 97%).
Reaction SMILES: [C:1]([C:4]1[CH:14]=[CH:13][C:7]([O:8][CH2:9][C:10]([OH:12])=[O:11])=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[CH2:15](O)[CH2:16][CH2:17][CH2:18][CH2:19][CH3:20].S(=O)(=O)(O)O.O>C1C=CC=CC=1>[C:1]([C:4]1[CH:14]=[CH:13][C:7]([O:8][CH2:9][C:10]([O:12][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])=[O:11])=[CH:6][CH:5]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)c1ccc(OCC(=O)O)cc1
Reactant: CCCCCCO
Agent: O=S(=O)(O)O
Solvent: c1ccccc1
Solvent: O
Product: CCCCCCOC(=O)COc1ccc(C(C)=O)cc1

Procedure:
A mixture of 4-acetylphenoxyacetic acid (20.0g.), n-hexanol (10.5g.) and concentrated sulphuric acid (2ml.) in benzene (100ml.) was heated under reflux for 6 hours using a water separator.cThe mixture was then evaporated and the residue dissolved in n-pentane (50ml.). The solution was washed with water (3 × 30ml.) sodium bicarbonate solution (1 × 50ml.) and water again (1 × 50ml.). The solution was evaporated and the residue chromatographed on alumina to give n-hexyl 4-acetylphenoxyacetate, I.R. peaks at 1760 and 1680 cm-1.