Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: OCCCN1C=C(C2C=CC(N[C:22]3[C:27]([C:28]([F:31])([F:30])[F:29])=[CH:26][N:25]=[C:24]([NH:32][C:33]4[CH:47]=[CH:46][C:36]([CH2:37][P:38](=[O:45])([O:42][CH2:43][CH3:44])[O:39][CH2:40][CH3:41])=[CH:35][C:34]=4[O:48][CH3:49])[N:23]=3)=C3C=2CN(C)C3=O)C=N1.[NH2:50][C:51]1[C:52]([C:67]([NH:69][CH3:70])=[O:68])=[N:53][C:54]([C:57]2[CH:58]=[N:59][N:60]([CH2:62][CH2:63][CH2:64][CH2:65][OH:66])[CH:61]=2)=[CH:55][CH:56]=1>>[OH:66][CH2:65][CH2:64][CH2:63][CH2:62][N:60]1[CH:61]=[C:57]([C:54]2[N:53]=[C:52]([C:67](=[O:68])[NH:69][CH3:70])[C:51]([NH:50][C:26]3[C:27]([C:28]([F:29])([F:30])[F:31])=[CH:22][N:23]=[C:24]([NH:32][C:33]4[CH:47]=[CH:46][C:36]([CH2:37][P:38](=[O:45])([O:42][CH2:43][CH3:44])[O:39][CH2:40][CH3:41])=[CH:35][C:34]=4[O:48][CH3:49])[N:25]=3)=[CH:56][CH:55]=2)[CH:58]=[N:59]1
Reactant: CCOP(=O)(Cc1ccc(Nc2ncc(C(F)(F)F)c(Nc3ccc(-c4cnn(CCCO)c4)c4c3C(=O)N(C)C4)n2)c(OC)c1)OCC
Reactant: CNC(=O)c1nc(-c2cnn(CCCCO)c2)ccc1N
Product: CCOP(=O)(Cc1ccc(Nc2ncc(C(F)(F)F)c(Nc3ccc(-c4cnn(CCCCO)c4)nc3C(=O)NC)n2)c(OC)c1)OCC
Yield: 40 %

Procedure:
Prepared analogously to Compound 1B using 3-amino-6-[1-(4-hydroxybutyl)-1H-pyrazol-4-yl]-N-methylpyridine-2-carboxamide (Compound 15C, 95 mg, 333 μmol) to afford 95 mg of the title compound (40%). 1H NMR (400 MHz, CD3OD) δ 8.98 (d, J=8.3 Hz, 1H), 8.42 (s, 1H), 8.28 (s, 1H), 8.20 (s, 1H), 7.76 (d, J=6.1 Hz, 1H), 7.64 (d, J=8.8 Hz, 1H), 7.01 (d, J=1.8 Hz, 1H), 6.90 (td, J=2.2, 8.1 Hz, 1H), 4.22 (t, J=7.1 Hz, 2H), 4.01-4.11 (m, 4H), 3.87 (s, 3H), 3.59 (t, J=6.4 Hz, 2H), 3.28-3.29 (m, 1H), 3.24 (s, 1H), 2.96 (s, 3H), 1.92-2.04 (m, 2H), 1.51-1.60 (m, 2H), 1.25 (t, J=7.1 Hz, 6H). MS (ESI): m/z 707.71 [M+H]+. UPLC: tR=1.25 min (UPLC-SQD: analytical—2 min).
Reaction SMILES: [CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:16])=[C:11](F)[C:12]=3[F:14])[C:7](=[O:17])[C:6]([C:18]([OH:20])=[O:19])=[CH:5]2)[CH2:3][CH2:2]1.[NH2:21][C@H:22]1[C@@H:26]([N:27]2[CH:31]=[CH:30][N:29]=[N:28]2)[CH2:25][NH:24][CH2:23]1>N1C=CC=CC=1>[NH2:21][C@H:22]1[C@@H:26]([N:27]2[CH:31]=[CH:30][N:29]=[N:28]2)[CH2:25][N:24]([C:11]2[C:12]([F:14])=[C:13]3[C:8]([C:7](=[O:17])[C:6]([C:18]([OH:20])=[O:19])=[CH:5][N:4]3[CH:1]3[CH2:3][CH2:2]3)=[CH:9][C:10]=2[F:16])[CH2:23]1
Reactant: N[C@@H]1CNC[C@@H]1n1ccnn1
Reactant: O=C(O)c1cn(C2CC2)c2c(F)c(F)c(F)cc2c1=O
Solvent: c1ccncc1
Product: N[C@@H]1CN(c2c(F)cc3c(=O)c(C(=O)O)cn(C4CC4)c3c2F)C[C@@H]1n1ccnn1
Temperature: 110 °C
Reaction time: 20 h

Procedure:
A mixture of 1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid (44 mg, 0.156 mmol) and cis-3-amino-4-(1,2,3-triazol-1-yl)pyrrolidine (60 mg, 0.39 mmol) in pyridine (5 ml) was heated at 110° C. for 2-3 h under nitrogen and then stirred at room temperature for 20 h. The reaction mixture was concentrated and the residue was washed with water and acetonitrile. The solid was dried under vacuum at 40° C. Yield: 43 mg (66%), m.p. 245°-47° C. 1H NMR (TFA) δ: 1.3-1.8 (m, 4H), 4.4-5.25 (m, 6H), 6.40 (m, 1H), 8.15 (d, 1H), 8.62 (s, 1H), 8.90 (s, 1H), 9.40 (s, 1H).
Reaction SMILES: Br[CH2:2][C:3]1[CH:4]=[CH:5][C:6]([N+:13]([O-:15])=[O:14])=[C:7]([CH:12]=1)[C:8]([O:10][CH3:11])=[O:9].C(=O)([O-])[O-].[K+].[K+].[NH:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1>CN(C=O)C>[N+:13]([C:6]1[CH:5]=[CH:4][C:3]([CH2:2][N:22]2[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)=[CH:12][C:7]=1[C:8]([O:10][CH3:11])=[O:9])([O-:15])=[O:14]
Reactant: C1CCNCC1
Reactant: COC(=O)c1cc(CBr)ccc1[N+](=O)[O-]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)c1cc(CN2CCCCC2)ccc1[N+](=O)[O-]
Temperature: 25 °C

Procedure:
Methyl 5-(bromomethyl)-2-nitrobenzoate was added to a DMF suspension of potassium carbonate and piperidine, followed by stirring at room temperature to obtain methyl 2-nitro-5-(piperidin-1-ylmethyl)benzoate (Dat, ES: 279). This compound was dissolved in acetic acid, iron powder was added thereto, followed by stirring at 60° C. to obtain methyl 2-amino-5-(piperidin-1-ylmethyl)benzoate (Dat, F: 249). Cyclohexanone and sodium triacetoxyborohydride were added to an acetic acid solution of this compound, followed by stirring at room temperature. By post-treating the reaction liquid, methyl 2-(cyclohexylamino)-5-(piperidin-1-ylmethyl)benzoate was obtained.
Reaction SMILES: Br[C:2]1[C:3]([OH:10])=[N:4][C:5]([CH3:9])=[N:6][C:7]=1[CH3:8].[C:11]([Zn]C#N)#[N:12]>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.CN(C)C=O>[OH:10][C:3]1[C:2]([C:11]#[N:12])=[C:7]([CH3:8])[N:6]=[C:5]([CH3:9])[N:4]=1
Reactant: Cc1nc(C)c(Br)c(O)n1
Reactant: N#C[Zn]C#N
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Product: Cc1nc(C)c(C#N)c(O)n1
Temperature: 140 °C
Reaction time: 12 h
Yield: 98.9 %

Procedure:
A mixture of 5-bromo-2,6-dimethylpyrimidin-4-ol (3.7 g, 18.3 mmol), dicyano zinc (10.7 g, 91.5 mmol) and tetrakis(triphenylphosphine)palladium (6.3 g, 5.1 mmol) and N,N-dimethylformamide (60 mL) was stirred at 140° C. for 12 hours. The mixture was concentrated to give a residue. The residue was purified by column chromatography (silica gel, dichloromethane/methanol=15:1) to give 4-hydroxy-2,6-dimethylpyrimidine-5-carbonitrile as a white solid (2.7 g, 99%). LRMS (M+H) m/z: calcd 149.06. found 149.
Reaction SMILES: Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[C:11]([O:15][C:16]([NH:18][CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([OH:27])[CH:22]=1)=[O:17])([CH3:14])([CH3:13])[CH3:12].C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[C:11]([O:15][C:16](=[O:17])[NH:18][CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([O:27][C:2]2[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=2)[CH:22]=1)([CH3:14])([CH3:12])[CH3:13]
Reactant: O=[N+]([O-])c1cccnc1Cl
Reactant: CC(C)(C)OC(=O)NCCc1cccc(O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)NCCc1cccc(Oc2ncccc2[N+](=O)[O-])c1
Temperature: 100 °C
Reaction time: 12 h
Yield: 93.7 %

Procedure:
A mixture of 2-chloro-3-nitropyridine (4.76 g, 30 mmols), N-tert-butoxycarbonyl-3-hydroxyphenethylamine (7.11 g, 30 mmols), potassium carbonate (4.14 g, 30 mmols) and N,N-dimethylformamide (50 ml) was stirred at 100° C. for 12 hours. The reaction mixture was cooled, then poured into water, and then extracted with ethyl acetate. The extract was washed with water, and then dried with anhydrous magnesium sulfate, and the solvent was evaporated away. The residue was purified through silica gel column chromatography to give an yellow oil of tert-butyl[2-[3-(3-nitro-2-pyridyloxy)phenyl]ethyl]carbamate (10.1 g, 92.5%).
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]([C:13]2[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[N:14]=2)=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:6]=1.CO[C:28](OC)([N:30]([CH3:32])[CH3:31])[CH3:29]>CN(C)C=O>[CH3:31][N:30]([CH3:32])[CH:28]([N:1]=[C:2]1[NH:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[C:4]([C:13]2[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[N:14]=2)[S:3]1)[CH3:29]
Reactant: Nc1nc(-c2ccccc2)c(-c2ccnc(Nc3ccccc3)n2)s1
Reactant: COC(C)(OC)N(C)C
Solvent: CN(C)C=O
Product: CC(N=c1[nH]c(-c2ccccc2)c(-c2ccnc(Nc3ccccc3)n2)s1)N(C)C
Temperature: 140 °C

Procedure:
A suspension of [4-(2-amino-4-phenyl-thiazol-5-yl)-pyrimidin-2-yl]-phenyl-amine (0.28 g, 0.81 mmol) in dimethylacetamide dimethylacetal (0.22 g, 1.62 mmol) and dimethylformamide (10 ml) is heated at 140° C. for 4 hours. After distilling off all volatile compounds the residue is purified by chromatography on silicagel (eluent: ethyl acetate/hexane) to give in form of a yellow powder, m.p. 196–197° C.
Reaction SMILES: [C:1]1([CH3:10])[CH:6]=[CH:5][C:4]([C:7](Cl)=[O:8])=[CH:3][CH:2]=1.[Cl-].[Al+3].[Cl-].[Cl-].[CH3:15][N:16]1[CH:20]=[CH:19][C:18]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[C:17]1[CH3:26]>ClC(Cl)C>[CH3:15][N:16]1[C:20]([C:7]([C:4]2[CH:5]=[CH:6][C:1]([CH3:10])=[CH:2][CH:3]=2)=[O:8])=[CH:19][C:18]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[C:17]1[CH3:26]
Reactant: CCOC(=O)c1ccn(C)c1C
Reactant: Cc1ccc(C(=O)Cl)cc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: CC(Cl)Cl
Product: CCOC(=O)c1cc(C(=O)c2ccc(C)cc2)n(C)c1C
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
Thirty-seven grams of p-toluoyl chloride (0.243 mole) is added to a suspension of 32.4 g. (0.243 mole) of aluminum chloride in 80 ml of dichloroethane. The resulting solution is then added dropwise to a solution of 40.7 g. (0.243 mole) of ethyl 1,2-dimethylpyrrole-3-carboxylate in 80 ml of dichloroethane cooled in an ice bath. After the addition is complete, the resulting solution is stirred at room temperature for 20 minutes, is refluxed for 20 minutes, and is then poured into an ice-3N hydrochlorice acid mixture. The organic phase is separated and is washed twice with concentrated sodium chloride solution, after which it is dried over magnesium sulfate. Evaporation of the solvent yields a residue from which the desired product crystallized. Further product is obtained by chromatography of the mother liquor over acid-washed alumina in hexane using benzene as the eluant. Evaporation of the first compound-bearing fractions yields the desired product. Recrystallization of the combined yields of product from 95% ethanol and then methanol gives as pure product ethyl 1,2-dimethyl-5-(p-toluoyl)pyrrole-3 -carboxylate; m.p. 98°-100° C.
Reaction SMILES: [NH2:1][C@@H:2]([CH:6]1[CH2:11][CH2:10][O:9][CH2:8][CH2:7]1)[C:3]([OH:5])=[O:4].C(=O)([O-])[O-].[Na+].[Na+].Cl[C:19]([O:21][CH3:22])=[O:20]>O>[CH3:22][O:21][C:19]([NH:1][C@@H:2]([CH:6]1[CH2:7][CH2:8][O:9][CH2:10][CH2:11]1)[C:3]([OH:5])=[O:4])=[O:20]
Reactant: COC(=O)Cl
Reactant: N[C@H](C(=O)O)C1CCOCC1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Product: COC(=O)N[C@H](C(=O)O)C1CCOCC1
Reaction time: 18 h

Procedure:
To (S)-2-amino-2-(tetrahydro-2H-pyran-4-yl)acetic acid (505 mg; 3.18 mmol; obtained from Astatech) in water (15 ml) was added sodium carbonate (673 mg; 6.35 mmol), and the resultant mixture was cooled to 0° C. and then methyl chloroformate (0.26 ml; 3.33 mmol) was added dropwise over 5 minutes. The reaction was allowed to stir for 18 hours while allowing the bath to thaw to ambient temperature. The reaction mixture was then partitioned between 1N HCl and ethyl acetate. The organic layer was removed and the aqueous layer was further extracted with 2 additional portions of ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo to afford Cap-170 a colorless residue. 1H NMR (500 MHz, DMSO-d6) δ ppm 12.65 (1 H, br s), 7.44 (1 H, d, J=8.24 Hz), 3.77-3.95 (3 H, m), 3.54 (3 H, s), 3.11-3.26 (2 H, m), 1.82-1.95 (1 H, m), 1.41-1.55 (2 H, m), 1.21-1.39 (2 H, m); LC/MS: Anal. Calcd. for [M+H]+ C9H16NO5: 218.1; found 218.1.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[C:7]([O:11][CH2:12][C:13](O)=[O:14])([CH3:10])([CH3:9])[CH3:8].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O>[C:7]([O:11][CH2:12][C:13]([N:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1)=[O:14])([CH3:10])([CH3:9])[CH3:8]
Reactant: CC(C)(C)OCC(=O)O
Reactant: C1COCCN1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Product: CC(C)(C)OCC(=O)N1CCOCC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 31.3 %

Procedure:
Morpholine (2.98 ml, 34.4 mmol), tert-Butoxy-acetic acid (4.485 g, 34.4 mmol) and HATU (13.093 g, 34.4 mmol) were dissolved in 15 ml dimethylformamide. The reaction mixture was stirred overnight at ambient temperature. It was extracted with ethyl acetate and the organic phase was washed with water, sodium bicarbonate solution, 1M HCl solution and finally with brine. The organic phase was dried over sodium sulfate, filtered, and concentrated to give 2-tert-Butoxy-1-morpholin-4-yl-ethanone (2.170 g, 10.78 mmol).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:20]=[CH:19][C:11]3[N:12]=[C:13]([NH:15][C:16](=[O:18])[CH3:17])[S:14][C:10]=3[CH:9]=2)[CH:5]=[CH:4][N:3]=1.[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH2:27][CH2:28][CH2:29][OH:30])[CH:22]=1>N1C=CC=CC=1>[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH2:27][CH2:28][CH2:29][O:30][C:2]2[N:7]=[C:6]([C:8]3[CH:20]=[CH:19][C:11]4[N:12]=[C:13]([NH:15][C:16](=[O:18])[CH3:17])[S:14][C:10]=4[CH:9]=3)[CH:5]=[CH:4][N:3]=2)[CH:22]=1
Reactant: CC(=O)Nc1nc2ccc(-c3ccnc(Cl)n3)cc2s1
Reactant: OCCCc1cccnc1
Solvent: c1ccncc1
Product: CC(=O)Nc1nc2ccc(-c3ccnc(OCCCc4cccnc4)n3)cc2s1
Temperature: 120 °C

Procedure:
N-(6-(2-Chloropyrimidin-4-yl)benzo[d]thiazol-2-yl)acetamide (59.4 mg, 195 μmol) and 3-pyridinepropanol (0.25 mL, 1.9 mmol) were suspended in pyridine (0.80 mL) in a microwave vial, which was then sealed and heated in a microwave (CEM brand) at 120° C. and 300 watts using a ramp time of 5 minutes and a run time of 20 minutes. The reaction was cooled to RT, concentrated, and purified on HPLC (10% to >95% MeCN/water with 0.1% TFA over 40 minutes) to afford N-(6-(2-(3-(pyridin-3-yl)propoxy)pyrimidin-4-yl)benzo[d]thiazol-2-yl)acetamide. MS (ESI pos. ion) m/z: 406. Calculated exact mass for C21H19N5O2S: 405. 1H NMR (400 MHz, DMSO-d6): 12.51 (s, 1H), 8.83 (d, J=5.5 Hz, 2H), 8.71 (d, J=5.0 Hz, 1H), 8.64 (d, J=5.5 Hz, 1H), 8.39 (d, J=8.0 Hz, 1H), 8.25 (d, J=8.5 Hz, 1H), 7.84-7.89 (m, 2H), 7.75 (d, J=5.0 Hz, 1H), 4.47 (t, J=7.5 Hz, 2H), 2.98 (t, J=7.5 Hz, 2H), 2.23 (s, 3H), 2.17-2.22 (m, 2H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:17]=[C:16]3[C:11]([CH2:12][CH2:13][CH2:14][C:15]3=[N:18][C:19]3[CH:20]=[C:21]([CH:30]=[CH:31][CH:32]=3)[O:22][CH2:23][C:24](OC(C)C)=[O:25])=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[Na]>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:17]=[C:16]3[C:11]([CH2:12][CH2:13][CH2:14][CH:15]3[NH:18][C:19]3[CH:20]=[C:21]([CH:30]=[CH:31][CH:32]=3)[O:22][CH2:23][CH2:24][OH:25])=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)OC(=O)COc1cccc(N=C2CCCc3ccc(-c4cccc(F)c4)cc32)c1
Agent: [Na]
Solvent: C1CCOC1
Product: OCCOc1cccc(NC2CCCc3ccc(-c4cccc(F)c4)cc32)c1
Temperature: 25 °C
Reaction time: 4 h
Yield: 79.5 %

Procedure:
To a solution of isopropyl 2-(3-((7-(3-fluorophenyl)-3,4-dihydronaphthalen-1(2H)-ylidene)amino)phenoxy)acetate (4 mg, 0.01 mmol) and THF (1 mL) was added sodium borohyride (22 mg, 0.58 mmol) at 0° C. The solution was stirred for 4 hours at room temperature. The reaction was quenched with saturated aqueous NaHCO3 (50 mL) and extracted with ethyl acetate (3×50 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated. The resulting crude residue was purified by combiflash (4 g column, hexanes→100% ethyl acetate/hexanes, gradient) to afford 3 mg (82%) of the title compound.
Reaction SMILES: [CH3:1][CH:2]([O:5][C:6]1[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][CH:7]=1)[CH2:3][CH3:4].Cl[CH2:14][CH2:15][NH:16][C:17](=[O:20])[O:18][CH3:19].C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[CH3:1][CH:2]([O:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][CH2:14][CH2:15][NH:16][C:17](=[O:20])[O:18][CH3:19])=[CH:10][CH:11]=1)[CH2:3][CH3:4]
Reactant: CCC(C)Oc1ccc(O)cc1
Reactant: COC(=O)NCCCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCC(C)Oc1ccc(OCCNC(=O)OC)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A mixture of 4-(1-methylpropoxy)phenol (9.2 mmol), methyl 2-chloroethylcarbamate (11.9 mmol), and potassium carbonate (18.4 mmol) in 20 ml of dimethylformamide (DMF) is heated at 85° for 18 hours. The reaction mixture is cooled to room temperature (RT), poured into water and extracted with ether. The combined ether extracts are washed with water until neutral, followed with brine and dried over calcium sulfate. The solvent is removed in vacuo and the residue is placed under high vacuum at 80° for ca. 2 hours to remove the excess methyl 2-chloroethylcarbamate. Purification by preparative thin layer chromatography (prep. TLC) gives methyl N-{2-[4-(1-methylpropoxy)phenoxy]ethyl}carbamate.
Reaction SMILES: Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])[CH:9]=2)[N:4]([Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])[CH:3]=1.IC.[C:28]([Li])(C)(C)C>>[C:22]([Si:19]([CH3:21])([CH3:20])[N:4]1[C:5]2[C:10](=[CH:9][C:8]([O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])=[CH:7][CH:6]=2)[C:2]([CH3:28])=[CH:3]1)([CH3:25])([CH3:24])[CH3:23]
Reactant: [Li]C(C)(C)C
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc2c(c1)c(Br)cn2[Si](C)(C)C(C)(C)C
Solvent: CI
Product: Cc1cn([Si](C)(C)C(C)(C)C)c2ccc(O[Si](C)(C)C(C)(C)C)cc12

Procedure:
In analogy to the procedure described in example 27 c], 3-bromo-1-(tert-butyl-dimethyl-silanyl)-5-(tert-butyl-dimethyl-silanyloxy)-1H-indole was reacted with 1-iodomethane in the presence of tert-butyllithium to give 1-(tert-butyl-dimethyl-silanyl)-5-(tert-butyl-dimethyl-silanyloxy)-3-methyl-1H-indole as brown viscous oil.
Reaction SMILES: [C:1]1([CH3:13])[CH:6]=[CH:5][C:4]([O:7][CH2:8][C:9]([O:11][CH3:12])=[O:10])=[CH:3][CH:2]=1.[Br:14]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl.C(Cl)Cl>[Br:14][CH2:13][C:1]1[CH:6]=[CH:5][C:4]([O:7][CH2:8][C:9]([O:11][CH3:12])=[O:10])=[CH:3][CH:2]=1
Reactant: COC(=O)COc1ccc(C)cc1
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClCCl
Solvent: ClC(Cl)(Cl)Cl
Product: COC(=O)COc1ccc(CBr)cc1
Yield: 56.1 %

Procedure:
To a solution of the methyl 2-(p-tolyloxy)acetate (3.10 g, 17.2 mmol) in carbon tetrachloride (60 mL) was added N-bromosuccinimide (3.57 g, 20 mmol) followed by benzoyl peroxide (463 mg, 1.9 mmol). The resulting solution was heated at reflux overnight, and then diluted with methylene chloride. The mixture was washed with brine, dried on MgSO4, and concentrated. The resulting colorless oil was purified by chromatography on silica gel (Hexane/ethyl acetate 9/1) to afford a colorless oil (2.5 g, 56%).
Reaction SMILES: [OH:1][C@@H:2]1[C@H:6]2[N:7](C(OCC3C=CC=CC=3)=O)[CH2:8][C@@H:9]([CH2:10][CH3:11])[C@H:5]2[O:4][CH2:3]1.[H][H]>[Pd].CO>[CH2:10]([C@@H:9]1[CH2:8][NH:7][C@@H:6]2[C@@H:2]([OH:1])[CH2:3][O:4][C@H:5]12)[CH3:11]
Reactant: CC[C@@H]1CN(C(=O)OCc2ccccc2)[C@H]2[C@@H]1OC[C@@H]2O
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: CC[C@@H]1CN[C@H]2[C@@H]1OC[C@@H]2O
Reaction time: 1.25 h

Procedure:
Methanol (2.0 mL) was added dropwise to a mixture of 10% palladium on charcoal (10 mg) and alcohol (113) (105 mg, 0.36 mmol) wider an atmosphere of argon. The argon was replaced by hydrogen then the suspension was stirred for 75 mins before filtering the mixture through celite in vacuo. The filter cake was washed with ethanol (3×10 mL) then the solvents removed in vacuo from the filtrate. The residue was azeotroped with toluene (2×3 in L) to obtain free base which was used without further purification.
Reaction SMILES: C([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][CH:17]([O:19][C:20](=[O:22])[CH3:21])[CH3:18])=[CH:12][CH:11]=2)=[CH:6][CH:5]=1)(=O)C.C(Cl)(Cl)Cl.ClC1C=CC=[C:30]([C:34]([O:36]O)=[O:35])C=1.S([O-])(O)=O.[Na+]>ClCCl>[C:34]([O:36][C:4]1[CH:5]=[CH:6][C:7]([C:10]2[CH:11]=[CH:12][C:13]([CH2:16][CH:17]([O:19][C:20](=[O:22])[CH3:21])[CH3:18])=[CH:14][CH:15]=2)=[CH:8][CH:9]=1)(=[O:35])[CH3:30]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CC(=O)OC(C)Cc1ccc(-c2ccc(C(C)=O)cc2)cc1
Agent: O=S([O-])O
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: ClCCl
Product: CC(=O)Oc1ccc(-c2ccc(CC(C)OC(C)=O)cc2)cc1
Yield: 96.7 %

Procedure:
29.6 g (0.1 mol) of (-)-4-acetyl-4'-(2-acetoxypropyl)biphenyl (XIX-13) ([α]D20 =-9.9° (C=1, CHCl3)} was charged into a four necked-flask provided with a thermometer and an agitator, and dissolved by adding 200 ml of dichloromethane. 20.7 g (0.12 mol) of m-chloroperbenzoic acid was added in this solution and agitated at reflux for 8 hours. After excess of m-chloroperbenzoic acid was decomposed by adding 10% aqueous solution of sodium hydrogen sulfite to the reaction mixture, the organic layer was washed with 10% aqueous solution of sodium bicarbonate and then with water, and dried an anhydrous magnesium sulfate. The resulting dichloromethane solution was concentrated under the reduced pressure to provide 30.2 g (yield: 97%) of (-)-4-acetoxy-4'-(2-acetoxypropyl)biphenyl (XVIII-13).
Reaction SMILES: [C:1]1([C@@H:7]2[CH2:11][O:10][C:9](=[O:12])[NH:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:13][C:14]1[N:19]=[C:18](Cl)[CH:17]=[CH:16][N:15]=1.[H-].[Na+]>CN(C=O)C.CCOC(C)=O>[Cl:13][C:14]1[N:19]=[C:18]([N:8]2[C@H:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH2:11][O:10][C:9]2=[O:12])[CH:17]=[CH:16][N:15]=1
Reactant: Clc1ccnc(Cl)n1
Reactant: O=C1N[C@H](c2ccccc2)CO1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: O=C1OC[C@@H](c2ccccc2)N1c1ccnc(Cl)n1
Temperature: 25 °C
Reaction time: 3 h
Yield: 54.2 %

Procedure:
A solution of (R)-4-phenyloxazolidin-2-one (2.9484 g, 18.07 mmol) and 2,4-dichloropyrimidine (3.1872 g, 21.39 mmol, 1.184 equiv) in DMF (30 mL) was treated with NaH (95%, 0.4773 g, 18.89 mmol, 1.046 equiv), then the resulting mixture (yellow to red cloudy) was stirred at room temperature for 3 h. The reaction mixture was diluted with EtOAc (200 mL), washed with sat. NH4Cl (75 mL) and 4% aqueous NaCl (2×100 mL), dried over Na2SO4, filtered and concentrated. Silica gel column chromatography (EtOAc/Heptane 0 to 40%) provided (R)-3-(2-chloropyrimidin-4-yl)-4-phenyloxazolidin-2-one (2.7020 g, white sticky solid) in 46.9% yield. 1H NMR (400 MHz, CD3OD) δ 8.47 (d, J=5.6 Hz, 1H), 8.18 (d, J=6.1 Hz, 1H), 7.38-7.30 (m, 5H), 5.81 (dd, J=8.6, 3.5 Hz, 1H), 4.88 (t, J=8.6 Hz, 1H), 4.37 (dd, J=8.6, 3.5 Hz, 1H); MS m/z 276.4 (M+H)+.
Reaction SMILES: [F:1][C:2]1[C:7]([F:8])=[C:6]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([I:16])=[CH:12][C:11]=2[F:17])[C:5]([NH2:18])=[CH:4][CH:3]=1.[CH3:19][C:20]1[O:21][C:22]([CH3:29])=[CH:23][C:24]=1[S:25](Cl)(=[O:27])=[O:26]>>[F:8][C:7]1[C:6]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([I:16])=[CH:12][C:11]=2[F:17])=[C:5]([NH:18][S:25]([C:24]2[CH:23]=[C:22]([CH3:29])[O:21][C:20]=2[CH3:19])(=[O:27])=[O:26])[CH:4]=[CH:3][C:2]=1[F:1]
Reactant: Cc1cc(S(=O)(=O)Cl)c(C)o1
Reactant: Nc1ccc(F)c(F)c1Nc1ccc(I)cc1F
Product: Cc1cc(S(=O)(=O)Nc2ccc(F)c(F)c2Nc2ccc(I)cc2F)c(C)o1

Procedure:
According to the general procedure B, 5,6-difluoro-N1-(2-fluoro-4-iodophenyl)benzene-1,2-diamine (0.182 mmol) was reacted with 2,5-dimethylfuran-3-sulfonyl chloride (0.5 mmol) to obtain N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino) phenyl)-2,5-dimethylfuran-3-sulfonamide. 1H NMR (300 MHz, CDCl3)) δ 2.2 (s, 3H), 2.3 (s, 3H), 5.8 (s, 1H), 6.0 (dt, 1H), 6.8 (s, 1H), 7.0 (q, 1H), 7.2 (d, 1H), 7.3 (m, 2H), 7.4 (dd, 1H).