Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C@@H:2]([C@H:4]1[C:10](=[O:11])[N:9]2[C@@H:5]1[C@@H:6]([CH3:53])[C:7]([S:25][C@@H:26]1[CH2:30][CH2:29][O:28][C@@H:27]1[CH2:31][NH:32][C:33](=[O:52])[C@@H:34]([NH:38]C(OCC1C=CC([N+]([O-])=O)=CC=1)=O)[CH:35]([CH3:37])[CH3:36])=[C:8]2[C:12]([O:14]CC1C=CC([N+]([O-])=O)=CC=1)=[O:13])[CH3:3].C(O)CCC>[Pd].O>[NH2:38][C@@H:34]([CH:35]([CH3:37])[CH3:36])[C:33]([NH:32][CH2:31][C@@H:27]1[C@H:26]([S:25][C:7]2[C@H:6]([CH3:53])[C@H:5]3[N:9]([C:10](=[O:11])[C@@H:4]3[C@H:2]([OH:1])[CH3:3])[C:8]=2[C:12]([OH:14])=[O:13])[CH2:30][CH2:29][O:28]1)=[O:52]
Reactant: CC(C)[C@H](NC(=O)OCc1ccc([N+](=O)[O-])cc1)C(=O)NC[C@H]1OCC[C@H]1SC1=C(C(=O)OCc2ccc([N+](=O)[O-])cc2)N2C(=O)[C@H]([C@@H](C)O)[C@H]2[C@H]1C
Agent: [Pd]
Solvent: O
Solvent: CCCCO
Product: CC(C)[C@H](N)C(=O)NC[C@H]1OCC[C@H]1SC1=C(C(=O)O)N2C(=O)[C@H]([C@@H](C)O)[C@H]2[C@H]1C
Reaction time: 8 h
Yield: 83.1 %

Procedure:
A mixture of 4-nitrobenzyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-{[(2R,3R)-2-({[(2S)-3-methyl-2-({[(4-nitrobenzyl)oxy]carbonyl}amino)-butanoyl]amino}methyl)tetrahydrofuran-3-yl]thio}-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (0.200 g), 50% wet 10% palladium on carbon (0.256 g), 1-butanol (20 ml) and water (20 ml) is hydrogenated in a Parr apparatus at 56 psi for 8 hours. The catalyst is then removed by filtration through diatomaceous earth and washed with 2×6 ml of water. The 1-butanol layer is extracted once with 6 ml of water. The combined aqueous solution (ca. 38 ml) is extracted twice with 2×10 ml of isopropyl acetate, concentrated under reduced pressure below 28° C. to ca. 20 ml and lyophilized to give 97.1 mg (83.0%) of the desired product as a slightly tan solid. MS (ES), m/z:442.3 (M+H)+; rotation [α]D25+42±1° (c 0.84, H2O); purity by analytical HPLC (100%).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[N:10][N:11]([CH2:19][C:20]([NH2:22])=[O:21])[C:12]=2[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:5]=[CH:6][CH:7]=1.[CH2:23]([N:25]([CH2:34][CH3:35])[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]N)[CH3:24].CC1C=C(C2C=NN(CC(OCC)=O)C=2C2C=CC=CC=2)C=CC=1.CC1C=C(CC(C2C=CC=CC=2)=O)C=CC=1>>[CH2:34]([N:25]([CH2:23][CH3:24])[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][NH:22][C:20](=[O:21])[CH2:19][N:11]1[C:12]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[C:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([CH3:1])[CH:3]=2)[CH:9]=[N:10]1)[CH3:35]
Reactant: Cc1cccc(-c2cnn(CC(N)=O)c2-c2ccccc2)c1
Reactant: CCN(CC)CCCCCCCN
Agent: CCOC(=O)Cn1ncc(-c2cccc(C)c2)c1-c1ccccc1
Agent: Cc1cccc(CC(=O)c2ccccc2)c1
Product: CCN(CC)CCCCCCCNC(=O)Cn1ncc(-c2cccc(C)c2)c1-c1ccccc1

Procedure:
By a process substantially similar to that of Example 30 it is contemplated that N-7-(diethylamino)heptyl]-4-(3-methylphenyl)-5-phenyl-1H-pyrazole-1-acetamide may be synthesized from N,N-diethyl-1,7-heptanediamine and ethyl 4-(3-methylphenyl)-5-phenyl-1H-pyrazole-1-acetate, which is synthesized by a process substantially similar to that of Example 1B from 2-(3-methylphenyl)-1-phenylethanone.
Reaction SMILES: Br.[NH2:2][C:3]1[S:4][C:5]([C:9](=O)[CH2:10]Br)=[C:6]([CH3:8])[N:7]=1.[NH2:13][C:14]1[C:19]([CH3:20])=[CH:18][CH:17]=[CH:16][N:15]=1>CC(N(C)C)=O>[NH2:2][C:3]1[S:4][C:5]([C:9]2[N:13]=[C:14]3[C:19]([CH3:20])=[CH:18][CH:17]=[CH:16][N:15]3[CH:10]=2)=[C:6]([CH3:8])[N:7]=1
Reactant: Cc1cccnc1N
Reactant: Cc1nc(N)sc1C(=O)CBr
Agent: Br
Solvent: CC(=O)N(C)C
Product: Cc1nc(N)sc1-c1cn2cccc(C)c2n1
Yield: 21.8 %

Procedure:
A solution of 2-amino-4-methyl-5-(2-bromoacetyl)thiazole hydrobromide (9.5 g) and 2-amino-3-methylpyridine (9.7 g) in dimethylacetamide (100 ml) was heated at 85° C. to 88° C. for 5 hours and the reaction mixture was evaporated in vacuo. To the residue was added water and the resulting mixture was acidified to pH 0.8 with 10% hydrochloric acid. The acidified solution was treated with charcoal and filtered. The filtrate was washed with ethyl acetate. The aqueous solution was adjusted to pH 9.0 with aqueous potassium carbonate and extracted with ethyl acetate. The extract was dried over magnesium sulfate and evaporated in vacuo. The residue was recrystallized from a mixture of ethyl acetate and tetrahydrofuran to give 2-(2-amino-4-methyl-5-thiazolyl)-8-methylimidazo[1,2-a]pyridine (1.6 g). mp 226° C. (dec.).
Reaction SMILES: [C:1]([O:4][CH:5]1[CH:10]=[CH:9][CH:8](O[Si](C(C)(C)C)(C)C)[O:7][CH2:6]1)(=[O:3])[CH3:2].C(=O)=O.CC(C)=O.C([SiH](CC)CC)C.B(F)(F)F.CCOCC>C(Cl)Cl>[C:1]([O:4][CH:5]1[CH:10]=[CH:9][CH2:8][O:7][CH2:6]1)(=[O:3])[CH3:2]
Reactant: CC(=O)OC1C=CC(O[Si](C)(C)C(C)(C)C)OC1
Agent: CC[SiH](CC)CC
Agent: FB(F)F
Agent: O=C=O
Solvent: CCOCC
Solvent: CC(C)=O
Solvent: ClCCl
Product: CC(=O)OC1C=CCOC1
Reaction time: 1 h
Yield: 77.6 %

Procedure:
6-(tert-Butyldimethylsilyloxy)-3,6-dihydro-2H-pyran-3-yl acetate (13.6 g, 49.9 mmol) was dissolved in DCM (250 mL), placed under a nitrogen atmosphere, and cooled to −30° C. (dry ice/acetone, until temperature was reached). Triethylsilane (15.95 mL, 100 mmol) was then added slowly via syringe, followed by drop wise addition of boron trifluoride etherate (7.59 mL, 59.9 mmol). The reaction was kept under nitrogen and slowly allowed to warm. After 1 h, the reaction mixture was quenched by additions of saturated sodium bicarbonate. After transferring to a separatory funnel, the organic layer was washed with water and brine, dried over sodium sulfate, filtered and condensed. The crude material was purified on a 340G SNAP Biotage column (0-80% ethyl acetate in hexane). Evaporation of clean fractions gave 3,6-dihydro-2H-pyran-3-yl acetate (5.5 g, 38.7 mmol, 77% yield) as a colorless oil; 1H NMR (400 MHz, CDCl3) δ ppm 5.09 (dtt, J=5.73, 2.21, 2.21, 1.17, 1.17 Hz, 1H), 4.19-4.28 (m, 1H), 4.04-4.15 (m, 1H), 3.89-3.98 (m, 1H), 3.76-3.84 (m, 1H), 2.10 (s, 3H).
Reaction SMILES: C(OC(=O)[NH:7][C@H:8]([C:32]1[NH:36][C:35]2[CH:37]=[CH:38][C:39]([C:41]3[CH:46]=[CH:45][C:44]([C:47]#[N:48])=[C:43]([F:49])[CH:42]=3)=[CH:40][C:34]=2[N:33]=1)[CH2:9][C:10](=[O:31])[NH:11]C(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)(C)(C)C.FC(F)(F)C(O)=O>>[NH2:7][C@H:8]([C:32]1[NH:36][C:35]2[CH:37]=[CH:38][C:39]([C:41]3[CH:46]=[CH:45][C:44]([C:47]#[N:48])=[C:43]([F:49])[CH:42]=3)=[CH:40][C:34]=2[N:33]=1)[CH2:9][C:10]([NH2:11])=[O:31]
Reactant: CC(C)(C)OC(=O)N[C@@H](CC(=O)NC(c1ccccc1)(c1ccccc1)c1ccccc1)c1nc2cc(-c3ccc(C#N)c(F)c3)ccc2[nH]1
Solvent: O=C(O)C(F)(F)F
Product: N#Cc1ccc(-c2ccc3[nH]c([C@@H](N)CC(N)=O)nc3c2)cc1F
Reaction time: 2.5 h
Yield: 66.3 %

Procedure:
(S)-tert-butyl(1-(5-(4-cyano-3-fluorophenyl)-1H-benzo[d]imidazol-2-yl)-3-oxo-3-(tritylamino)propyl)carbamate (Preparation 17, 28 mg, 0.042 mmol) was dissolved in trifluoroacetic acid (1.1 mL, 14 mmol) and stirred for 2.5 hours. The reaction mixture was concentrated in vacuo, azeotroped with methanol (3×), and purified by silica gel column chromatography eluting with 0-100% CMA80/methylene chloride to afford the title compound (9 mg, 37%) as a white solid.
Reaction SMILES: [F:1][C:2]([F:11])([F:10])[C:3]1[CH:4]=[C:5]([OH:9])[CH:6]=[N:7][CH:8]=1.[F:12][C:13]1[CH:14]=[C:15]([CH:18]=[C:19]([F:22])[C:20]=1F)[CH:16]=[O:17]>>[F:12][C:13]1[CH:14]=[C:15]([CH:18]=[C:19]([F:22])[C:20]=1[O:9][C:5]1[CH:6]=[N:7][CH:8]=[C:3]([C:2]([F:1])([F:10])[F:11])[CH:4]=1)[CH:16]=[O:17]
Reactant: Oc1cncc(C(F)(F)F)c1
Reactant: O=Cc1cc(F)c(F)c(F)c1
Product: O=Cc1cc(F)c(Oc2cncc(C(F)(F)F)c2)c(F)c1

Procedure:
The title compound was prepared by a procedure similar to that described for D30 starting from 5-(trifluoromethyl)pyridin-3-ol and 3,4,5-trifluorobenzaldehyde
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][CH2:11][C@H:10]([C:14]([NH:16][CH:17]3[CH2:22][CH2:21][CH:20]([CH3:23])[CH2:19][CH2:18]3)=[O:15])[CH2:9]2)[CH:5]=[C:4]([C:24]2[CH:29]=[CH:28][C:27]([C:30]#[N:31])=[C:26](F)[CH:25]=2)[N:3]=1.CCN(C(C)C)C(C)C.[NH2:42][NH2:43]>CCO>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][CH2:11][C@H:10]([C:14]([NH:16][CH:17]3[CH2:22][CH2:21][CH:20]([CH3:23])[CH2:19][CH2:18]3)=[O:15])[CH2:9]2)[CH:5]=[C:4]([C:24]2[CH:25]=[C:26]3[C:27]([C:30]([NH2:31])=[N:42][NH:43]3)=[CH:28][CH:29]=2)[N:3]=1
Reactant: CC1CCC(NC(=O)[C@H]2CCCN(c3cc(-c4ccc(C#N)c(F)c4)nc(N)n3)C2)CC1
Reactant: NN
Solvent: CCO
Solvent: CCN(C(C)C)C(C)C
Product: CC1CCC(NC(=O)[C@H]2CCCN(c3cc(-c4ccc5c(N)n[nH]c5c4)nc(N)n3)C2)CC1
Temperature: 150 °C
Yield: 64.1 %

Procedure:
Into a microwave tube, (3S)-1-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-N-(4-methylcyclohexyl)-3-piperidinecarboxamide (190 mg, 0.435 mmol), 3 mL of EtOH, Hunig's base (0.30 mL, 1.74 mmol), and hydrazine anhydrous (0.082 mL, 2.61 mmol) were added, and the yellow mixture was heated at 150° C. for 180 minutes under microwave conditions. The solution turned black. LCMS showed mainly product. The black solids were filtered and the yellow filtrate was evaporated. The yellow residue was sonicated in EtOAc at 50° C., and the solid was filtered. This material was then sonicated in water at 50° C., and the solid was filtered and washed with water to afford the title compound (125 mg) as a light yellow solid. LC-MS (ES) m/z=449 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 0.87 (m, 3H), 0.89-1.94 (m, 13H), 2.18-2.44 (m, 1H), 2.78-3.05 (m, 2H), 3.76 (m, 1H), 4.39 (m, 2H), 5.38 (s, 2H), 6.12 (s, 2H), 6.62 (s, 1H), 7.54-7.79 (m, 3H), 7.90-7.99 (m, 1H), 11.51 (s, 1H).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[CH:13][C:14]2[CH:19]=[CH:18][C:17]([S:20][CH3:21])=[CH:16][CH:15]=2)[C:9](=[N:11][OH:12])[CH3:10])=[CH:4][CH:3]=1.BrC1C=CC(C=C(C2C=CC=CC=2)C(=NO)C)=CC=1>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:9]([CH3:10])=[N:11][O:12][C:13]=2[C:14]2[CH:15]=[CH:16][C:17]([S:20][CH3:21])=[CH:18][CH:19]=2)=[CH:6][CH:7]=1
Reactant: CSc1ccc(C=C(C(C)=NO)c2ccc(Br)cc2)cc1
Agent: CC(=NO)C(=Cc1ccc(Br)cc1)c1ccccc1
Product: CSc1ccc(-c2onc(C)c2-c2ccc(Br)cc2)cc1

Procedure:
The title compound was prepared according to the procedure of step 3 in the Example 190 using 3-(4-bromophenyl)-4-(4-methylthiophenyl)-3-buten-2-one oxime, instead of 4-(4-bromophenyl)-3-phenyl-3-buten-2-one oxime.
Reaction SMILES: [H-].[Na+].[O:3]=[C:4]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[O:19][C:6]2([CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]2)[CH2:5]1.C[CH2:27][O:28]CC.C(OCC)=O>CO>[OH:28][CH:27]=[C:5]1[C:6]2([CH2:7][CH2:8][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:10][CH2:11]2)[O:19][C:20]2[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:4]1=[O:3]
Reactant: CC(C)(C)OC(=O)N1CCC2(CC1)CC(=O)c1ccccc1O2
Reactant: CCOCC
Agent: [H-]
Agent: [Na+]
Solvent: CO
Solvent: CCOC=O
Product: CC(C)(C)OC(=O)N1CCC2(CC1)Oc1ccccc1C(=O)C2=CO
Temperature: 25 °C
Reaction time: 8 h
Yield: 36 %

Procedure:
NaH (1.89 g, 47.3 mmol) was added in small portions to a mixture of tert-butyl 4-oxospiro[chroman-2,4′-piperidine]-1′-carboxylate (3.0 g, 9.5 mmol), Et2O (75 mL), and MeOH (120 μL) at rt. The mixture was allowed to stir for 1 h before ethyl formate (9.2 mL, 110 mmol) was added dropwise. The mixture was allowed to stir at 25° C. overnight before it was quenched with 1M aqueous HCl. The layers were separated and the aqueous layer was extracted with ethyl acetate (3×). The combined organics were washed with brine, dried over sodium sulfate, and concentrated in vacuo. Column chromatography (0-100% ethyl acetate in hexanes) provided tert-butyl 3-(hydroxymethylene)-4-oxospiro[chroman-2,4′-piperidine]-1′-carboxylate (1.2 g, 36%) as a light yellow solid. ESI-MS m/z calc. 345.2, found 246.2 (M+1-Boc)+; Retention time: 2.62 minutes (4 min run). 1H NMR (400 MHz, CDCl3) δ 15.13 (d, J=8.3 Hz, 1H), 7.93 (d, J=8.1 Hz, 1H), 7.88 (dd, J=7.8, 1.5 Hz, 1H), 7.50-7.44 (m, 1H), 7.06 (t, J=7.5 Hz, 1H), 6.96 (d, J=8.2 Hz, 1H), 4.10-3.95 (m, 2H), 3.25-3.15 (m 2H), 2.15 (d, J=12.7 Hz, 2H), 1.80-1.66 (m, 2H), 1.47 (s, 9H).
Reaction SMILES: [C:1]([O:5][C:6]([C:9]([CH2:12][CH2:13]I)([F:11])[F:10])([F:8])[F:7])([F:4])([F:3])[F:2].CNC=[O:18].O>CCOCC>[C:1]([O:5][C:6]([C:9]([CH2:12][CH2:13][OH:18])([F:11])[F:10])([F:8])[F:7])([F:4])([F:3])[F:2]
Reactant: FC(F)(F)OC(F)(F)C(F)(F)CCI
Reactant: CNC=O
Solvent: CCOCC
Solvent: O
Product: OCCC(F)(F)C(F)(F)OC(F)(F)F
Temperature: 150 °C
Reaction time: 0.25 h
Yield: 71 %

Procedure:
A mixture of CF3OCF2CF2CH2CH2I, (92 g, 0.27 mol) and N-methyl-formamide (119 mL), was heated to 150° C. for 26 hours. Then the reaction was cooled to 100° C., followed by the addition of water to separate the crude ester. Ethyl alcohol (30 mL) and p-toluene sulfonic acid (1.03 g) were added to the crude ester, and the reaction was stirred at 70° C. for 15 minutes. Then ethyl formate and ethyl alcohol were distilled out to give a crude product. The crude product was dissolved in ether, washed with aqueous sodium sulfite, water, and brine in turn, then dried over magnesium sulfate. The product was then distilled to give 44 g of CF3OCF2CF2CH2CH2OH (compound B1) in 71% yield.
Reaction SMILES: F[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[C:8]1[O:9][C:10]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][C:11]=2[N:12]=1.[CH2:21]([SH:24])[CH2:22][CH3:23].C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>O>[CH2:21]([S:24][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[C:8]1[O:9][C:10]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][C:11]=2[N:12]=1)[CH2:22][CH3:23]
Reactant: CCCS
Reactant: Fc1cnccc1-c1nc2cc(C(F)(F)F)ccc2o1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCCSc1cnccc1-c1nc2cc(C(F)(F)F)ccc2o1
Temperature: 50 °C
Yield: 89.4 %

Procedure:
A mixture of 0.28 g of 2-(3-fluoropyridin-4-yl)-5-(trifluoromethyl)benzoxazole, 0.15 g of 1-propanethiol, 0.40 g of potassium carbonate and 2 ml of DMF was stirred while heating at 50° C. for one hour. The reaction mixture was cooled to room temperature, and then water was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with a saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 0.30 g of 2-(3-propylthiopyridin-4-yl)-5-(trifluoromethyl)benzoxazole (hereinafter, referred to as “active compound 42”).
Reaction SMILES: [CH3:1][O:2][CH2:3][C:4]1[CH:5]=[N:6][C:7]([N:10]2[CH2:15][CH2:14][CH:13]([C@H:16]3[CH2:18][C@H:17]3[CH2:19][CH2:20][OH:21])[CH2:12][CH2:11]2)=[N:8][CH:9]=1.[Br:22][C:23]1[CH:28]=[CH:27][C:26](O)=[CH:25][C:24]=1[Cl:30].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1(C)C=CC=CC=1>[Br:22][C:23]1[CH:28]=[CH:27][C:26]([O:21][CH2:20][CH2:19][C@@H:17]2[CH2:18][C@@H:16]2[CH:13]2[CH2:14][CH2:15][N:10]([C:7]3[N:8]=[CH:9][C:4]([CH2:3][O:2][CH3:1])=[CH:5][N:6]=3)[CH2:11][CH2:12]2)=[CH:25][C:24]=1[Cl:30]
Reactant: COCc1cnc(N2CCC([C@H]3C[C@H]3CCO)CC2)nc1
Reactant: Oc1ccc(Br)c(Cl)c1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Product: COCc1cnc(N2CCC([C@H]3C[C@H]3CCOc3ccc(Br)c(Cl)c3)CC2)nc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
2-[(1S,2R)-2-{1-[5-(methoxymethyl)pyrimidin-2-yl]piperidin-4-yl}cyclopropyl]ethanol (670 mg, 2.30 mmol) was dissolved in toluene (5 ml) and 4-bromo-3-chlorophenol (525 mg, 2.53 mmol), triphenylphosphine (905 mg, 3.45 mmol), and DIAD (671 μl, 3.45 mmol) added and the mixture stirred at RT overnight. The mixture was concentrated in vacuo and the residue purified by column chromatography on SiO2 using a Biotage 50M cartridge using a gradient eluant of 0-50% EtOAc:hexanes to afford the title compound. LC/MS (m/z): 481 (M+H)+.
Reaction SMILES: [OH:1][CH2:2][CH:3]([CH2:5][OH:6])[OH:4].C1(C)C=CC(S(O)(=O)=O)=CC=1.[C:18](OC)(OC)([O:20][CH3:21])[CH3:19].C(=O)([O-])[O-].[Na+].[Na+]>C(Cl)Cl>[OH:1][CH2:2][CH:3]1[CH2:5][O:6][C:18]([O:20][CH3:21])([CH3:19])[O:4]1
Reactant: OCC(O)CO
Reactant: COC(C)(OC)OC
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Product: COC1(C)OCC(CO)O1
Reaction time: 18 h
Yield: 97 %

Procedure:
Example: A 1-liter round-bottomed flask was equipped with a pressure equalizing addition funnel was flushed with nitrogen and charged with 41.5 grams (451 mmol.) of glycerol, 750 ml. of methylene chloride and 100 mg. of p-toluenesulfonic acid. Trimethyl orthoacetate, 56.9 grams (473 mmol), was added over 5 minutes at room temperature, with stirring. The stirring was continued for 18 hours followed by addition of 1 gram of anhydrous sodium carbonate. The mixture was stirred for one additional hour and filtered. The solvent was stripped under vacuum to yield 65 grams (97% of theoretical) of 4-hydroxymethyl-2-methoxy-2-methyl-1,3-dioxolane as a clear oil. Its molecular structure was confirmed by proton and carbon-13 nuclear magnetic resonance spectroscopy. A 3-necked 2 liter round-bottomed flask was equipped with a mechanical stirrer, condenser, thermometer, and addition funnel. The flask was charged with 0.5 g methyltrialkylammonium chloride, 100 mL chloroform, 30 mL distilled water, and 32 g of 50 percent aqueous sodium hydroxide. The flask was immersed in a ice-water bath and cooled to approximately 10° C. while stirring rapidly followed by addition of 30 g (0.2 mol) 4-hydroxymethyl-2-methoxy-2-methyl-1,3-dioxolane. A solution of 20.2 g terephthaloyl chloride (0.1 mol) in chloroform was added to the flask through the addition funnel over a 60 minute period maintaining the reaction temperature at approximately 10° C. or lower. After the addition of the acid chloride was complete, the reaction was stirred for additional 60 minutes. The layers were separated and the chloroform layer was washed twice with 500 mL distilled water, dried over anhydrous sodium sulfate and vacuum stripped to yield the product.
Reaction SMILES: [C:1]([C:5]1[N:6]=[C:7]([N:16]2[CH2:20][CH2:19][C:18]([F:22])([F:21])[CH2:17]2)[C:8]2[N:13]=[N:12][N:11]([CH2:14][CH3:15])[C:9]=2[N:10]=1)([CH3:4])([CH3:3])[CH3:2].C(C1N=C(N2CCC(F)(F)C2)C2N=NNC=2N=1)(C)(C)C.BrCC1[CH:50]=[CH:49][CH:48]=[C:47]([Cl:51])[C:46]=1[Cl:52]>>[C:1]([C:5]1[N:6]=[C:7]([N:16]2[CH2:20][CH2:19][C:18]([F:21])([F:22])[CH2:17]2)[C:8]2[N:13]=[N:12][N:11]([CH2:14][C:15]3[CH:50]=[CH:49][CH:48]=[C:47]([Cl:51])[C:46]=3[Cl:52])[C:9]=2[N:10]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: Clc1cccc(CBr)c1Cl
Reactant: CCn1nnc2c(N3CCC(F)(F)C3)nc(C(C)(C)C)nc21
Agent: CC(C)(C)c1nc(N2CCC(F)(F)C2)c2nn[nH]c2n1
Product: CC(C)(C)c1nc(N2CCC(F)(F)C2)c2nnn(Cc3cccc(Cl)c3Cl)c2n1

Procedure:
In analogy to the procedure described for the synthesis of 5-tert-butyl-7-(3,3-difluoro-pyrrolidin-1-yl)-3-ethyl-3H-[1,2,3]triazolo[4,5-d]pyrimidine (example 61), the title compound was prepared from 5-tert-butyl-7-(3,3-difluoropyrrolidin-1-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and 1-(bromomethyl)-2,3-dichlorobenzene and isolated as colorless gum (6.7 mg, 37%). MS(m/e): 441.3 (MH+).
Reaction SMILES: I[C:2]1[C:10]([N+]([O-])=O)=[CH:9][CH:8]=[C:7]2[C:3]=1/[C:4](=[CH:15]/[C:16]1[NH:17][CH:18]=[CH:19][C:20]=1[O:21][CH3:22])/[C:5](=[O:14])[NH:6]2.[OH:23][CH2:24][CH:25]=[CH:26]B(O)O.C([O-])([O-])=O.[Na+].[Na+]>C(COC)OC.O.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>[OH:23][CH2:24][CH:25]=[CH:26][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4](=[CH:15][C:16]1[NH:17][CH:18]=[CH:19][C:20]=1[O:21][CH3:22])[C:5](=[O:14])[NH:6]2
Reactant: OCC=CB(O)O
Reactant: COc1cc[nH]c1/C=C1\C(=O)Nc2ccc([N+](=O)[O-])c(I)c21
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: [Na+]
Solvent: O
Solvent: COCCOC
Product: COc1cc[nH]c1C=C1C(=O)Nc2cccc(C=CCO)c21
Temperature: 85 °C
Reaction time: 8 h

Procedure:
To a stirred solution of (Z)-1,3-dihydro-4-iodo-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2H-indol-2-one (50 mg, 0.14 mmol) (Starting Material 2 supra) in dimethoxyethane (5 mL) was added 3-hydroxy-1-propenyl-boronic acid (from Example 66 above) (42 mg, 0.418 mmol), tetrakis(triphenylphosphine)palladium(0) (39 mg, 0.034 mmol) (Aldrich) and 2M Na2CO3 solution in H2O (0.34 mL). The reaction mixture was stirred at 85° C. overnight in a pressure tube. The solvent was removed in vacuo, and the residue was purified by silica gel chromatography (Hex:EtOAc=5:1) to provide 1,3-dihydro-4-(3-hydroxy-propenyl)-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-indol-2-one as a yellow solid. (Yield 22 mg, 53%).
Reaction SMILES: [Si:1]([O:8][C@@H:9]1[C@@:28]2([CH3:29])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:27]2[CH2:26][CH2:25][C@@:24]2([CH3:30])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C@H:21]([OH:23])[CH3:22])[CH2:12][C@@H:11]([O:31][Si:32]([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:42]/[CH:43]=[CH:44]\[C:45]([CH3:55])([O:47][Si:48]([CH2:53][CH3:54])([CH2:51][CH3:52])[CH2:49][CH3:50])[CH3:46]>O1CCCC1>[Si:1]([O:8][C@@H:9]1[C@@:28]2([CH3:29])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:27]2[CH2:26][CH2:25][C@@:24]2([CH3:30])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C@H:21]([O:23][CH2:42]/[CH:43]=[CH:44]\[C:45]([CH3:55])([O:47][Si:48]([CH2:51][CH3:52])([CH2:53][CH3:54])[CH2:49][CH3:50])[CH3:46])[CH3:22])[CH2:12][C@@H:11]([O:31][Si:32]([C:35]([CH3:37])([CH3:36])[CH3:38])([CH3:33])[CH3:34])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: C[C@@H](O)C1=CC[C@H]2C3=CC=C4C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C
Reactant: CC[Si](CC)(CC)OC(C)(C)/C=C\CBr
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC[Si](CC)(CC)OC(C)(C)/C=C\CO[C@H](C)C1=CC[C@H]2C3=CC=C4C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C
Yield: 85.2 %

Procedure:
Under the same conditions as in Example 83, 1α,3β-bis(tert-butyldimethylsilyloxy)-20(R)-hydroxypregna-5,7,16-triene (60.0 mg, 0.107 mmol), sodium hydride (60%, 17.1 mg, 0.428 mmol), 15-crown-5(10 μl) and (Z)-1-bromo-4-methyl-4-triethylsilyloxy-2-pentene (125 mg, 0.428 mmol) were reacted in tetrahydrofuran (1 ml) and worked up, and then the residue was purified by preparative thin layer chromatography (0.5 mm×2, hexane:ethyl acetate=30:1, developed once) to give the title compound as a colorless oil (70.3 mg, 85%).
Reaction SMILES: Br[C:2]1[CH:24]=[C:23]([Cl:25])[C:5]([C:6]([C:8]2[C:16]3[C:11](=[C:12]([NH:17][C:18]([CH:20]4[CH2:22][CH2:21]4)=[O:19])[N:13]=[CH:14][CH:15]=3)[NH:10][CH:9]=2)=[O:7])=[C:4]([Cl:26])[CH:3]=1.[N-:27]=[N+]=[N-].[Na+].CNCCNC.CS(C)=O>O>[NH2:27][C:2]1[CH:24]=[C:23]([Cl:25])[C:5]([C:6]([C:8]2[C:16]3[C:11](=[C:12]([NH:17][C:18]([CH:20]4[CH2:22][CH2:21]4)=[O:19])[N:13]=[CH:14][CH:15]=3)[NH:10][CH:9]=2)=[O:7])=[C:4]([Cl:26])[CH:3]=1
Reactant: [N-]=[N+]=[N-]
Reactant: O=C(c1c(Cl)cc(Br)cc1Cl)c1c[nH]c2c(NC(=O)C3CC3)nccc12
Agent: CNCCNC
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: Nc1cc(Cl)c(C(=O)c2c[nH]c3c(NC(=O)C4CC4)nccc23)c(Cl)c1
Temperature: 110 °C
Yield: 53.7 %

Procedure:
N-[3-(4-Bromo-2,6-dichlorobenzoyl)-1H-pyrrolo[2,3-c]pyridin-7-yl]cyclopropanecarboxamide (0.5 g, 1.1 mmol) was taken in a reaction vial, followed by addition of sodium azide (0.286 g, 4.4 mmol), cuprous iodide (0.063 g, 0.3 mmol), N,N′-dimethylethane-1,2-diamine (0.058 g, 0.6 mmol) and dimethylsulfoxide (12 mL). The vial was sealed properly and heated at 110° C. for overnight. The reaction mixture was cooled to room temperature and water (100 mL) was added, extracted with ethyl acetate (3×150 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product was purified by silica gel (100-200 mesh) column chromatography using 2% methanol in dichloromethane to afford pure N-[3-(4-amino-2,6-dichlorobenzoyl)-1H-pyrrolo[2,3-c]pyridin-7-yl]cyclopropanecarboxamide (0.23 g, 47%).