Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([C@H]1COC(=O)N1[C:14](=[O:24])[C@H:15]([C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=1)[CH3:16])C1C=CC=CC=1.[BH4-].[Na+]>C1COCC1.O>[F:23][C:20]1[CH:19]=[CH:18][C:17]([C@H:15]([CH3:16])[CH2:14][OH:24])=[CH:22][CH:21]=1
Reactant: C[C@H](C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1)c1ccc(F)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: C[C@H](CO)c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 97.2 %

Procedure:
To a room-temperature solution of (S)-4-benzyl-3-((S)-2-(4-fluorophenyl)propanoyl)oxazolidin-2-one (1.8 g, 5.5 mmol, 1.0 equiv) in THF (18 mL) was added a solution of NaBH4 (1.0 g, 26.4 mmol, 4.8 equiv) in water (6.0 mL). The reaction mixture was stirred for 3 h at room temperature and then quenched by the careful addition of aq. 1M HCl. The reaction mixture was diluted with water and ethyl acetate. The layers were separated and the organic layer was subsequently washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. Purification by silica gel chromatography (10-75% EtOAc/Hexanes) provided the title compound (0.824 g, 97%).
Reaction SMILES: [CH2:1]([N:5]1[C:10]2[CH:11]=[N:12][NH:13][C:9]=2[C:8](=[O:14])[N:7]([CH2:15][CH2:16][CH2:17][CH3:18])[C:6]1=[O:19])[CH2:2][CH2:3][CH3:4].[CH2:20]([S:23](Cl)(=[O:25])=[O:24])[CH2:21][CH3:22].C(Cl)Cl.CCOC(C)=O>C(Cl)Cl>[CH2:1]([N:5]1[C:10]2[CH:11]=[N:12][N:13]([S:23]([CH2:20][CH2:21][CH3:22])(=[O:25])=[O:24])[C:9]=2[C:8](=[O:14])[N:7]([CH2:15][CH2:16][CH2:17][CH3:18])[C:6]1=[O:19])[CH2:2][CH2:3][CH3:4]
Reactant: CCCS(=O)(=O)Cl
Reactant: CCCCn1c(=O)c2[nH]ncc2n(CCCC)c1=O
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CCCCn1c(=O)c2c(cnn2S(=O)(=O)CCC)n(CCCC)c1=O
Temperature: 23 °C
Reaction time: 3 h
Yield: 92 %

Procedure:
To 500 mg (2.6-2.8 mmol/g resin) of piperidinomethyl polystyrene resin in 25 mL CH2Cl2 was added 280 mg (1.06 mmol) of 4,6-dibutyl-1,4-dihydro-pyrazolo[4,3-d]pyrimidine-5,7-dione followed by 166 mg (1.17 mmol) of propanesulfonyl chloride. The resulting solution was stirred at 23° C. for 3 h after which time TLC showed that all starting material (4/1 CH2Cl2 /EtOAc; Rf =0.15) had been consumed. The reaction mixture was filtered, the filtered cake washed with 3×5 mL CH2Cl2, and the combined organics were evaporated to give crude yellow oil. Flash chromatography on silica gel, eluting with CH2Cl2 /EtOAc (40/1 to 10/1) gave 359 mg (0.97 mmol, a 92% yield) of the title compound as a yellow solid. mp: 44-48° C.; 1H NMR (300 MHz, CDCl3); δ 0.93-1.17 (m, 9H), 1.35-1.44 (m, 4H), 1.61-1.83 (m, 4H), 2.06-2.33 (m, 2H), 3.51-3.68 (m, 2H), 3.85 (t, J=7.5 Hz, 2H), 4.02 (t, J=7.4 Hz, 2H), 7.88 (s, 1H); IR (KBr, cm-1): 3231w, 2960m, 1719m, 1675s, 1620m, 1387m, 1289m, 1171m, 1066m; MS (ES) m/z (relative intensity): 371 (M+ +H, 100). Anal. Calcd. for C16H26N4O4S: C, 51.87; H, 7.07, N, 15.12. Found: C, 46.22; H, 6.65; N, 11.91
Reaction SMILES: COC1C=CC(C[O:8][CH2:9][CH2:10][CH2:11][C@@:12]2(C3C=CC=CC=3)[O:17][C:16](=[O:18])[N:15]([C@H:19]([C:21]3[CH:26]=[CH:25][C:24]([CH2:27]C(OC)=O)=[CH:23][CH:22]=3)[CH3:20])[CH2:14][CH2:13]2)=CC=1.C[Mg]Br>C1COCC1>[OH:17][C:12]([CH3:13])([CH3:11])[CH2:27][C:24]1[CH:23]=[CH:22][C:21]([C@@H:19]([N:15]2[CH2:14][CH2:13][C@:12]([CH2:11][CH2:10][CH2:9][OH:8])([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[O:17][C:16]2=[O:18])[CH3:20])=[CH:26][CH:25]=1
Reactant: COC(=O)Cc1ccc([C@H](C)N2CC[C@](CCCOCc3ccc(OC)cc3)(c3ccccc3)OC2=O)cc1
Agent: C[Mg]Br
Solvent: C1CCOC1
Product: C[C@@H](c1ccc(CC(C)(C)O)cc1)N1CC[C@](CCCO)(c2ccccc2)OC1=O
Reaction time: 3 h
Yield: 25.9 %

Procedure:
To a solution of methyl 2-(4-((S)-1-((R)-6-(3-(4-methoxybenzyloxy)propyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)ethyl)phenyl)acetate (100 mg, 0.188 mmol) in THF (2 mL) was added methylmagnesium bromide (0.3 mL, 3 mol/L) at −78° C. The formed mixture was stirred for 3 h. The reaction was quenched by aqueous solution of NH4Cl. The organic phase was separated and concentrated to provide the crude product, which was purified by TLC to give (R)-3-((S)-1-(4-(2-hydroxy-2-methylpropyl)phenyl)ethyl)-6-(3-hydroxypropyl)-6-phenyl-1,3-oxazinan-2-one (10 mg, 10%). 1H NMR (CDCl3): δ=1.08 (d, 6H), 1.19 (m, 2H), 1.42 (d, 3H), 1.64 (m, 2H), 1.84 (m, 2H), 2.04-2.19 (m, 4H), 2.53 (s, 2H), 2.80 (m, 1H), 3.29 (t, 2H), 3.72 (s, 3H), 4.25 (s, 2H), 5.54 (q, 1H), 6.74 (m, 5H), 6.82 (m, 2H), 7.10 (m, 3H), 7.23 (m, 4H).
Reaction SMILES: [F:1][C:2]([F:9])([F:8])[CH2:3][CH2:4][C:5](O)=[O:6].[CH2:10]([C:13]1[C:19]([OH:20])=[CH:18][CH:17]=[CH:16][C:14]=1[OH:15])[CH2:11][CH3:12]>OS(C(F)(F)F)(=O)=O>[OH:15][C:14]1[CH:16]=[CH:17][C:18]([C:5](=[O:6])[CH2:4][CH2:3][C:2]([F:9])([F:8])[F:1])=[C:19]([OH:20])[C:13]=1[CH2:10][CH2:11][CH3:12]
Reactant: O=C(O)CCC(F)(F)F
Reactant: CCCc1c(O)cccc1O
Agent: O=S(=O)(O)C(F)(F)F
Product: CCCc1c(O)ccc(C(=O)CCC(F)(F)F)c1O

Procedure:
Using the procedure in Example 51, step 1, 4,4,4-trifluoro-butyric acid and 2-(n-propyl)resorcinol were condensed in triflic acid to form 1,3-dihydroxy-2-(n-propyl)-4-(4,4,4-trifluorobutyryl)benzene
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([CH3:8])[C:5]([CH:9]([CH2:14][CH2:15][CH3:16])[C:10]([O:12][CH3:13])=[O:11])=[C:4]([C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=2)[N:3]=1.[N:24]1[C:33]2[C:28](=[C:29](B(O)O)[CH:30]=[CH:31][CH:32]=2)[CH:27]=[CH:26][CH:25]=1.C(N(CC)C(C)C)(C)C>COCCOC.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:8][C:6]1[C:5]([CH:9]([CH2:14][CH2:15][CH3:16])[C:10]([O:12][CH3:13])=[O:11])=[C:4]([C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=2)[N:3]=[C:2]([C:29]2[CH:30]=[CH:31][CH:32]=[C:33]3[C:28]=2[CH:27]=[CH:26][CH:25]=[N:24]3)[N:7]=1
Reactant: CCCC(C(=O)OC)c1c(C)nc(Cl)nc1-c1ccc(C)cc1
Reactant: OB(O)c1cccc2ncccc12
Agent: [Pd]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(C(C)C)C(C)C
Solvent: COCCOC
Solvent: O
Product: CCCC(C(=O)OC)c1c(C)nc(-c2cccc3ncccc23)nc1-c1ccc(C)cc1
Yield: 65.8 %

Procedure:
Methyl 2-(2-chloro-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoate (100 mg; 0.300 mmol), quinolin-5-ylboronic acid (156 mg; 0.901 mmol), tetrakis(triphenylphosphine) palladium(0) (34.7 mg; 0.030 mmol) were placed in a 5 mL reaction tube and dissolved in a mixture of degassed DME (1.50 mL) and water (0.5 mL). N,N-Diisopropylethylamine (0.185 mL; 1.202 mmol) was added, the tube was sealed and irradiated in a microwave oven at 130° C. for 1 h. The reaction mixture was partitioned between brine and dichloromethane, filtered over a phase separator filter (1PS) and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel using a linear gradient of ethylacetate (10-80%) in heptane to give 84 mg (43%) of the title compound as a colorless oil.
Reaction SMILES: Cl.[Br:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][NH2:10])=[CH:5][CH:4]=1.C(N(CC)CC)C.[Cl:18][C:19]1[CH:27]=[CH:26][C:22]([C:23](Cl)=[O:24])=[CH:21][CH:20]=1>C(OCC)C>[Br:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]([C:23](=[O:24])[C:22]2[CH:26]=[CH:27][C:19]([Cl:18])=[CH:20][CH:21]=2)[NH2:10])=[CH:5][CH:4]=1
Reactant: O=C(Cl)c1ccc(Cl)cc1
Reactant: NNc1ccc(Br)cc1
Agent: Cl
Solvent: CCOCC
Solvent: CCN(CC)CC
Product: NN(C(=O)c1ccc(Cl)cc1)c1ccc(Br)cc1
Reaction time: 16 h

Procedure:
A mixture consisting of 44.7 g. (0.20 mole) p-bromophenylhydrazine hydrochloride, 250 ml. diethyl ether, 70 ml. (0.504 mole) triethylamine, and 35.0 g. (0.20 mole) p-chlorobenzoyl chloride in 50 ml. diethyl ether (mixed in that order at -5° to -15°C. during 20 minutes) was stirred continuously for about 16 hrs. at about 25° C. The reaction mixture was filtered, and the solids on the filter were washed with water and then recrystallized from 95% ethanol. There was thus obtained 15.5 g. p-chlorobenzoic acid (p-bromophenyl)hydrazide having a melting point of 185° C. (dec.). An analytical sample melting at 184.5°C. (dec.) was obtained after two recrystallizations from ethyl acetate.
Reaction SMILES: [F:1][C:2]([F:25])([F:24])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[O:13][N:12]=[C:11]([C:14]3[CH:23]=[CH:22][C:17]([C:18]([O:20]C)=[O:19])=[CH:16][CH:15]=3)[CH:10]=2)=[CH:5][CH:4]=1.[OH-].[Na+].O1CCCC1.Cl>O.CO>[F:25][C:2]([F:1])([F:24])[C:3]1[CH:4]=[CH:5][C:6]([C:9]2[O:13][N:12]=[C:11]([C:14]3[CH:23]=[CH:22][C:17]([C:18]([OH:20])=[O:19])=[CH:16][CH:15]=3)[CH:10]=2)=[CH:7][CH:8]=1
Reactant: COC(=O)c1ccc(-c2cc(-c3ccc(C(F)(F)F)cc3)on2)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Solvent: CO
Product: O=C(O)c1ccc(-c2cc(-c3ccc(C(F)(F)F)cc3)on2)cc1
Temperature: 60 °C
Reaction time: 1 h
Yield: 76.8 %

Procedure:
A mixture of methyl 4-[5-(4-trifluoromethylphenyl)-3-isoxazolyl]benzoate (0.486 g), 1 M aqueous sodium hydroxide solution (4 ml), tetrahydrofuran (20 ml) and methanol (20 ml) was stirred at 60° C. for 1 hr. After cooling, the reaction mixture was poured into water and 1 M hydrochloric acid (15 ml) was added. The crystals were collected by filtration and recrystallized from ethanol to give 4-[5-(4-trifluoromethylphenyl)-3-isoxazolyl]benzoic acid (0.358 g, yield 77%) as a colorless crystalline powder. melting point: >300° C.
Reaction SMILES: N.C(OCC)C.C([S:14][C:15]1[C:16](=[O:30])[CH:17]=[C:18]([S:22]CC2C=CC=CC=2)[C:19](=[O:21])[CH:20]=1)C1C=CC=CC=1.[Na]>C(O)C>[SH:14][C:15]1[CH:20]=[C:19]([OH:21])[C:18]([SH:22])=[CH:17][C:16]=1[OH:30]
Reactant: O=C1C=C(SCc2ccccc2)C(=O)C=C1SCc1ccccc1
Agent: N
Agent: [Na]
Solvent: CCOCC
Solvent: CCO
Product: Oc1cc(S)c(O)cc1S
Reaction time: 2.5 h

Procedure:
Ammonia was condensed (ca 200 ml) into 150 ml of dry diethylether in a 3-necked flask, with external cooling. Then 9.0 g (0.0256 mole) of 2,5-dibenzylmercapto-p-benzoquinone was dissolved into the liquid. Sodium (5.9 g, 0.256 mole) cut into fine pieces was added portionwise with efficient stirring. After stirring for an additional 2.5 hours, abs. ethanol (20 ml) was added and the ammonia was evaporated. Water (170 ml) was added to the reaction product and it was extracted with 2×30 ml of ether. The aqueous phase was then acidified to pH 1-2, with conc. hydrochloric acid, and extracted with 3×80 ml of ether. The ether extracts were collected, dried (Na2SO4), the solvent evaporated leaving a fluffy light brown glistening residue, 4.3 g (90%).
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]([O:8][C@@:9]1([C:44](SCC#N)=[O:45])[C@:40]2([CH3:41])[C@H:12]([C@H:13]3[C@H:37]([C@@H:38]([OH:42])[CH2:39]2)[C@@:17]2([CH3:43])[CH2:18][C:19]4[CH:20]=[N:21][N:22]([C:25]5[CH:30]=[CH:29][C:28]([F:31])=[C:27]([CH2:32][O:33][CH2:34][CH:35]=[CH2:36])[CH:26]=5)[C:23]=4[CH:24]=[C:16]2[CH2:15][CH2:14]3)[CH2:11][CH2:10]1)=[O:7].[CH3:50][NH2:51]>C(#N)C.C(O)C>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]([O:8][C@@:9]1([C:44](=[O:45])[NH:51][CH3:50])[C@:40]2([CH3:41])[C@H:12]([C@H:13]3[C@H:37]([C@@H:38]([OH:42])[CH2:39]2)[C@@:17]2([CH3:43])[CH2:18][C:19]4[CH:20]=[N:21][N:22]([C:25]5[CH:30]=[CH:29][C:28]([F:31])=[C:27]([CH2:32][O:33][CH2:34][CH:35]=[CH2:36])[CH:26]=5)[C:23]=4[CH:24]=[C:16]2[CH2:15][CH2:14]3)[CH2:11][CH2:10]1)=[O:7]
Reactant: C=CCOCc1cc(-n2ncc3c2C=C2CC[C@@H]4[C@H]([C@@H](O)C[C@@]5(C)[C@H]4CC[C@]5(OC(=O)c4ccco4)C(=O)SCC#N)[C@@]2(C)C3)ccc1F
Reactant: CN
Solvent: CCO
Solvent: CC#N
Product: C=CCOCc1cc(-n2ncc3c2C=C2CC[C@@H]4[C@H]([C@@H](O)C[C@@]5(C)[C@H]4CC[C@]5(OC(=O)c4ccco4)C(=O)NC)[C@@]2(C)C3)ccc1F
Reaction time: 3 h

Procedure:
In a 100 mL round-bottomed flask was dissolved the product obtained in Example 77 (75 mg, 0.11 mmol) in acetonitrile (2.5 mL) to give a yellow solution. 33% methanamine (2.5 mL, 20.19 mmol) in ethanol was added. The mixture was stirred in a closed flask for 3 hours, monitoring the reaction by LC-MS. When almost all of the starting material had been consumed, the volatiles were removed in vacuo. The crude mixture was purified on preparative HPLC (acetonitrile/water), and 15 mg (25%) was obtained of the desired product as a white solid after freeze-drying the pure fractions.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=O)[C@@H:10]([NH:12][C:13]2[N:21]=[CH:20][N:19]=[C:18]3[C:14]=2[N:15]=[CH:16][N:17]3C2CCCCO2)[CH3:11])=[C:4]([NH:29][C:30]2[CH:35]=[CH:34][N:33]=[CH:32][N:31]=2)[CH:3]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:45])=CC=1>C1COCC1.CCOC(C)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[S:45])[C@@H:10]([NH:12][C:13]2[N:21]=[CH:20][N:19]=[C:18]3[C:14]=2[N:15]=[CH:16][NH:17]3)[CH3:11])=[C:4]([NH:29][C:30]2[CH:35]=[CH:34][N:33]=[CH:32][N:31]=2)[CH:3]=1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: C[C@H](Nc1ncnc2c1ncn2C1CCCCO1)C(=O)Nc1ccc(F)cc1Nc1ccncn1
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: C[C@H](Nc1ncnc2[nH]cnc12)C(=S)Nc1ccc(F)cc1Nc1ccncn1
Yield: 12.2 %

Procedure:
(S)—N-[4-Fluoro-2-(pyrimidin-4-ylamino)phenyl]-2-[9-(tetrahydro-pyran-2-yl)-9H-purin-6-ylamino]propionamide (88 mg, 0.18 mmol) and Lawesson's reagent (298 mg, 0.74 mmol) were heated at reflux in THF (4 mL) under nitrogen for 16 h. Further Lawesson's reagent (150 mg, 0.37 mmol) was added and the reaction refluxed for a further 24 h. The reaction mixture was cooled, diluted with EtOAc (30 mL) and extracted with 1M HCl (2×5 mL). The aqueous extracts were basified with Na2CO3 and extracted with EtOAc (2×20 mL). The combined organic extracts were dried (Na2SO4), concentrated in vacuo and purified by column chromatography (Si—PCC, gradient 0-10% (9:1 MeOH/0.880 NH3) in DCM to give the title compound as a colourless gum, (9 mg, 12%). LCMS (Method B): RT 1.88 min [M+H]+ 410.09
Reaction SMILES: ClC1C=C(Cl)C=CC=1C1C(C2NC=CN=2)=CN=C(CCN)N=1.Cl[C:24]1[N:29]=[C:28]([N:30]([CH3:32])[CH3:31])[C:27]([N+:33]([O-:35])=[O:34])=[CH:26][CH:25]=1.[Cl:36][C:37]1[CH:42]=[C:41]([Cl:43])[CH:40]=[CH:39][C:38]=1[C:44]1[C:49]([C:50]2[NH:51][CH:52]=[CH:53][N:54]=2)=[CH:48][N:47]=[C:46]([NH:55][CH2:56][CH2:57][NH:58]C2C=CC([N+]([O-])=O)=C(OC)N=2)[N:45]=1>>[Cl:36][C:37]1[CH:42]=[C:41]([Cl:43])[CH:40]=[CH:39][C:38]=1[C:44]1[C:49]([C:50]2[NH:54][CH:53]=[CH:52][N:51]=2)=[CH:48][N:47]=[C:46]([NH:55][CH2:56][CH2:57][NH:58][C:24]2[N:29]=[C:28]([N:30]([CH3:32])[CH3:31])[C:27]([N+:33]([O-:35])=[O:34])=[CH:26][CH:25]=2)[N:45]=1
Reactant: CN(C)c1nc(Cl)ccc1[N+](=O)[O-]
Reactant: COc1nc(NCCNc2ncc(-c3ncc[nH]3)c(-c3ccc(Cl)cc3Cl)n2)ccc1[N+](=O)[O-]
Agent: NCCc1ncc(-c2ncc[nH]2)c(-c2ccc(Cl)cc2Cl)n1
Product: CN(C)c1nc(NCCNc2ncc(-c3ncc[nH]3)c(-c3ccc(Cl)cc3Cl)n2)ccc1[N+](=O)[O-]

Procedure:
{6-[(2-{[4-(2,4-dichlorophenyl)-5-imidazol-2-ylpyrimidin-2-yl]amino}ethyl)amino]-3-nitro(2-pyridyl)}dimethylamine was prepared from [4-(2,4-dichlorophenyl)-5-imidazol-2-ylpyrimidin-2-ylethylamine and 6-chloro-2-dimethylamino-3-nitro pyridine in accordance with the procedure described above for the preparation of [4-(2,4-dichlorophenyl)-5-imidazol-2-ylpyrimidin-2-yl]{2-[(6-methoxy-5-nitro(2-pyridyl))amino]ethyl}amine.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]1[CH:9]([NH2:15])[CH2:8][CH2:7][CH2:6][C:5]2=1.Cl[C:17]1[N:22]=[C:21]([CH3:23])[CH:20]=[C:19]([CH3:24])[N:18]=1>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]1[CH:9]([NH:15][C:17]3[N:22]=[C:21]([CH3:23])[CH:20]=[C:19]([CH3:24])[N:18]=3)[CH2:8][CH2:7][CH2:6][C:5]2=1
Reactant: Cc1cc(C)nc(Cl)n1
Reactant: NC1CCCc2c1[nH]c1ccc(Cl)cc21
Product: Cc1cc(C)nc(NC2CCCc3c2[nH]c2ccc(Cl)cc32)n1

Procedure:
6-Chloro-N-(4,6-dimethylpyrimidin-2-yl)-2,3,4,9-tetrahydro-1H-carbazol-1-amine was prepared from 6-chloro-2,3,4,9-tetrahydro-1H-carbazol-1-amine and 2-chloro-4,6-dimethylpyrimidine in a similar manner as described above to give 6 mg (8% yield) of a pale yellow oil. 1H-NMR (CDCl3): δ 9.23 (s, 1H), 7.45 (s, 1H), 7.16 (d, 1H), 7.07 (d, 1H), 6.42 (s, 1H), 5.25 (m, 1H), 5.20 (m, 1H), 2.70 (m, 2H), 2.35 (s, 6H), 2.29 (m, 1H), 2.03-1.83 (m, 3H); MS m/z 327 (M+1).
Reaction SMILES: N1C=CC=CC=1.[Si:7]([N:14]1[CH:17]([CH2:18][CH:19]([OH:31])[CH2:20][C:21]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[O:22])[CH2:16][C:15]1=[O:32])([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8]>C(Cl)Cl.[O-2].[O-2].[O-2].[Cr+6]>[Si:7]([N:14]1[CH:17]([CH2:18][C:19](=[O:31])[CH2:20][C:21]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[O:22])[CH2:16][C:15]1=[O:32])([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8]
Reactant: CC(C)(C)[Si](C)(C)N1C(=O)CC1CC(O)CC(=O)OCc1ccccc1
Agent: [Cr+6]
Agent: [O-2]
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(C)(C)[Si](C)(C)N1C(=O)CC1CC(=O)CC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 73.2 %

Procedure:
Anhydrous CrO3 (2.274 g, 22.74 mmol) is added to a solution of anhydrous pyridine (3.597 g, 45.48 mmol) in anhydrous CH2Cl2 (60 ml). After stirring at room temperature (25° C.) for 15 mins, the reaction mixture is treated all at once with a solution of N-(t-butyldimethylsilyl)-4-(3-benzyloxycarbonyl-2-hydroxypropyl)-azetidin-2-one (1.432 g, 3.79 mmol) in anhydrous CH2Cl2 (25 ml). The resulting mixture is stirred at 25° C. for 5 mins. The CH2Cl2 layer is decanted from the dark, gummy residue which is triturated with more CH2Cl2. The combined CH2Cl2 phase is evaporated i.v. The residue is triturated with diethylether (Et2O) (100 ml) in several portions and the Et2O extracts are filtered to remove chromium salts. The ethereal filtrate is washed with 5% NaHCO3, 1N HCl, 5% NaHCO3 and brine, dried with MgSO4, filtered, and evaporated i.v. to yield N-(t-butyldimethylsilyl)-4-(3-benzyloxycarbonyl-2-oxopropyl)-azetidin-2-one (1.042 g) as a pale yellow oil: ir (neat) 5.72 (3 poorly resolved peaks), 7.59 7.98, 8.42, and 11.93 cm-1 ; nmr (CDCl3)δ 0.18 (s, 3), 0.22 (s, 3), 0.97 (s, 9), 2.53 (dd, 1), 2.63 (dd, 1), 3.13 (dd, 1), 3.28 (dd, 1), 3.47 (s,2), 3.88 (m, 1), 5.17 (s, 2), and 7.33 (s, 5); mass spectrum m/e 360, 318, and 2.76.
Reaction SMILES: COC[O:4][C:5]1[CH:10]=[CH:9][C:8]([CH:11]=[CH:12][C:13](=[O:15])[CH3:14])=[CH:7][C:6]=1[O:16][CH3:17]>CO.Cl>[OH:4][C:5]1[CH:10]=[CH:9][C:8]([CH:11]=[CH:12][C:13](=[O:15])[CH3:14])=[CH:7][C:6]=1[O:16][CH3:17]
Reactant: COCOc1ccc(C=CC(C)=O)cc1OC
Agent: Cl
Solvent: CO
Product: COc1cc(C=CC(C)=O)ccc1O
Temperature: 50 °C
Reaction time: 0.25 h
Yield: 73.4 %

Procedure:
1-(4-Methoxymethyloxy-3-methoxyphenyl)-1-buten-3-one (35j, 0.40 g, 1.7 mmol) was dissolved in methanol (40 ml) and stirred for 15 min at 50° C. Hydrochloric acid (3 drops) was added and the mixture stirred for 18 hr at 65° C. The methanol was evaporated and the resulting residue extracted into ethyl acetate, washed with saturated sodium chloride, dried over magnesium sulfate, filtered and evaporated to afford a solid. The crude solid was chromatographed on silica gel with ethyl acetate/hexane to give 0.24 g (74%) of an orange-yellow solid: mp 120-122° C. [expected mp 128-129° C.]; 1H NMR δ 2.34 (s, 3H), 3.91 (s, 3H), 5.98 (s, 1H), 6.56 (d, 1H, J=16.1 Hz), 6.91 (d, 1H, J=8.2 Hz), 7.04 (m, 2H), 7.43 (d, 1H, J=16.3 Hz); 13C NMR: δ 27.3, 56.0, 109.3, 114.8, 123.4, 124.9, 126.9, 143.6, 146.8, 148.2, 198.2.
Reaction SMILES: [C:1]1(O)C=CC=CC=1.[13CH4].[C:9]([C:17]1[CH:27]=[CH:26][C:20]([O:21][CH:22](C)[CH2:23][OH:24])=[CH:19][CH:18]=1)([CH2:12][C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:11])[CH3:10]>>[C:9]([C:17]1[CH:18]=[CH:19][C:20]([O:21][CH2:22][CH:23]([OH:24])[CH3:1])=[CH:26][CH:27]=1)([CH2:12][C:13]([CH3:14])([CH3:15])[CH3:16])([CH3:10])[CH3:11]
Reactant: Oc1ccccc1
Reactant: CC(CO)Oc1ccc(C(C)(C)CC(C)(C)C)cc1
Agent: [13CH4]
Product: CC(O)COc1ccc(C(C)(C)CC(C)(C)C)cc1

Procedure:
A 250 mL 2-neck flask was charged with 20.6 g (0.10 mol) of 4-tert-octylphenol obtained from Aldrich Chemical Co., a catalytic amount of dry, ground potassium carbonate (1.38 g, 0.010 mol) obtained from EM Science, Inc., a stir bar, and 95%. ethanol (70 mL) under argon. The side arm was then stoppered, and a condenser with an argon inlet was attached to the center neck. Stirring was commenced to dissolve the phenol, then cold propylene oxide (8.4 mL, 7.0 g, 0.12 mol) obtained from Aldrich Chemical Co. was added. The reaction was refluxed 3 hours, allowed to cool, and the ethanol was removed by rotary evaporation. The colorless oil was dissolved in 120 mL ethyl ether, and washed twice successively with 5% aqueous sodium hydroxide, followed by water. After drying over anhydrous MgSO4, the ether was evaporated off to give 25.3 g of crude product, which contained about 22 mol % unreacted phenol, and about 7 mol % of the 2-(4-tert-octyl-phenoxy)-1-propanol isomer. The product was purified by dissolving in 100 mL hexanes, and extracting with 4×50 mL 5% NaOH in 15:85 v/v water/methanol. The methanol layers were back-extracted with 50 mL hexanes obtained from EM Science, Inc. The hexanes layers were dried over anhydrous MgSO4, and the hexanes removed under vacuum to afford a combined yield of 13.3 g (50%) of material that contained less than 1% unreacted phenol. The structure of the compound was corroborated by proton (1H) and carbon-13 NMR spectrometry. Proton NMR revealed the material to contain about 7 mol % of the 2-(4-tert-octyl-phenoxy)-1-propanol isomer.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.Cl[C:10]1[CH:11]=[CH:12][C:13]([N+:18]([O-:20])=[O:19])=[C:14]([CH:17]=1)[C:15]#[N:16].O.[OH-].[Na+]>CN(C)C=O>[N+:18]([C:13]1[CH:12]=[CH:11][C:10]([O:8][C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)=[CH:17][C:14]=1[C:15]#[N:16])([O-:20])=[O:19]
Reactant: Oc1ccc(Cl)cc1
Reactant: N#Cc1cc(Cl)ccc1[N+](=O)[O-]
Agent: [Na+]
Agent: [OH-]
Solvent: CN(C)C=O
Solvent: O
Product: N#Cc1cc(Oc2ccc(Cl)cc2)ccc1[N+](=O)[O-]
Reaction time: 18 h
Yield: 52.6 %

Procedure:
Sodium hydride (60% in mineral oil), 1.5 grams (0.038 mole) was washed in petroleum ether. The petroleum ether was decanted, and the sodium hydride was suspended in about 20 mL of N,N-dimethylformamide. The suspension was stirred, and solutions of 4.5 grams (0.035 mole) of 4-chlorophenol in 20 mL of N,N-dimethylformamide and 5.0 grams (0.027 mole) of 5-chloro-2-nitrobenzonitrile in 20 mL of N,N-dimethylformamide were added, respectively. Upon completion of addition, the reaction mixture was warmed to reflux where it stirred for about 18 hours. The reaction mixture was then cooled and poured into a mixture of 500 mL of water and 50 mL of aqueous 2N sodium hydroxide. The mixture was stirred for about 15 minutes, then it was allowed to stand for about 18 hours. The resultant solid was collected by filtration and recrystallized from ethanol, yielding 3.9 grams of 2-nitro-5-(4-chlorophenoxy)benzonitrile, mp 120°-122° C. The NMR spectrum was consistent with the proposed structure.
Reaction SMILES: [CH2:1]([CH:3]1[O:5][CH2:4]1)Cl.[N+:6]([C:9]1[CH:10]=[C:11]([OH:19])[CH:12]=[CH:13][C:14]=1[NH:15][C:16](=[O:18])[CH3:17])([O-:8])=[O:7]>[OH-].[Na+]>[N+:6]([C:9]1[CH:10]=[C:11]([CH:12]=[CH:13][C:14]=1[NH:15][C:16](=[O:18])[CH3:17])[O:19][CH2:1][CH:3]1[O:5][CH2:4]1)([O-:8])=[O:7]
Reactant: ClCC1CO1
Reactant: CC(=O)Nc1ccc(O)cc1[N+](=O)[O-]
Agent: [Na+]
Agent: [OH-]
Product: CC(=O)Nc1ccc(OCC2CO2)cc1[N+](=O)[O-]
Reaction time: 48 h

Procedure:
150 ml of epichlorohydrin are added, at ambient temperature, to a solution of 0.376 mol (73.7 g) of 3-nitro-4-acetylaminophenol in 375 ml of 1.1N sodium hydroxide solution. The reaction medium is left to stand at ambient temperature for 48 hours, with thorough stirring, and the expected product which has precipitated is then filtered off. After drying in vacuo and recrystallisation from benzene, this product melts at 123° C.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([C:13]([CH3:16])([CH3:15])[CH3:14])=[N:10][C:9]=2[C:17]2[C:18]([F:24])=[C:19]([CH:21]=[CH:22][CH:23]=2)[NH2:20])[CH:5]=[CH:4][N:3]=1.[CH3:25][Zn]C>>[CH3:14][C:13]([C:11]1[S:12][C:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([CH3:25])[N:7]=2)=[C:9]([C:17]2[C:18]([F:24])=[C:19]([CH:21]=[CH:22][CH:23]=2)[NH2:20])[N:10]=1)([CH3:16])[CH3:15]
Reactant: CC(C)(C)c1nc(-c2cccc(N)c2F)c(-c2ccnc(Cl)n2)s1
Reactant: C[Zn]C
Product: Cc1nccc(-c2sc(C(C)(C)C)nc2-c2cccc(N)c2F)n1

Procedure:
Following a procedure analogous to the procedure described in Example 25 using 3-[5-(2-chloro-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluoroaniline (1.0 g, 2.76 mmol) and dimethylzinc (2.76 mL, 5.51 mmol), the title compound was obtained as an off white solid (0.8 g, 85% yield). MS (ESI): 343 [M+H]+.