Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:4][C:5]1([CH3:45])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[N:17]=[C:18]([C:20]4[CH:21]=[C:22]([C:26]5[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:27]=5[OH:33])[CH:23]=[CH:24][CH:25]=4)[CH:19]=[C:15]3[N:14]=[C:13]([CH3:34])[C:12]=2[C@H:35]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])[C:36]([O:38][CH3:39])=[O:37])[CH2:7][CH2:6]1)[CH:2]=[CH2:3].[CH3:46][C@@H:47](O)[CH2:48][CH:49]=[CH2:50].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1.CCOCC>[CH2:1]([O:4][C:5]1([CH3:45])[CH2:6][CH2:7][N:8]([C:11]2[N:16]3[N:17]=[C:18]([C:20]4[CH:21]=[C:22]([C:26]5[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:27]=5[O:33][C@H:49]([CH2:48][CH:47]=[CH2:46])[CH3:50])[CH:23]=[CH:24][CH:25]=4)[CH:19]=[C:15]3[N:14]=[C:13]([CH3:34])[C:12]=2[C@H:35]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])[C:36]([O:38][CH3:39])=[O:37])[CH2:9][CH2:10]1)[CH:2]=[CH2:3]
Reactant: C=CC[C@@H](C)O
Reactant: C=CCOC1(C)CCN(c2c([C@H](OC(C)(C)C)C(=O)OC)c(C)nc3cc(-c4cccc(-c5cc(F)ccc5O)c4)nn23)CC1
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: CCOCC
Product: C=CCOC1(C)CCN(c2c([C@H](OC(C)(C)C)C(=O)OC)c(C)nc3cc(-c4cccc(-c5cc(F)ccc5O[C@@H](C)CC=C)c4)nn23)CC1
Reaction time: 2 h
Yield: 80.1 %

Procedure:
To a solution of (S)-methyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(5′-fluoro-2′-hydroxy-[1,1′-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.19 g, 0.31 mmol, 1 equiv), (R)-pent-4-en-2-ol (0.095 mL, 0.92 mmol, 3 equiv), and PPh3 (0.16 g, 0.62 mmol, 2 equiv) in THF (1.54 mL) was added DEAD (0.098 mL, 0.62 mmol, 2 equiv). After stirring 2 h, dilute with ether and wash with water. The ether layer was dried (MgSO4) and concentrated in vacuo. The crude product was purified by flash column chromatography (0-60% EtOAc in hexane) to provide the product as a white foam (0.17 g, 81%). 1H NMR (500 MHz, CDCl3) [note: 4H of piperidine not observed and are likely very broad] δ 8.16 (s, 1H), 8.08-7.99 (m, 1H), 7.61-7.56 (m, 1H), 7.51 (d, J=7.6 Hz, 1H), 7.16 (dd, J=9.1, 2.8 Hz, 1H), 7.04-6.95 (m, 2H), 6.92-6.82 (m, 1H), 6.08-5.97 (m, 1H), 5.74 (s, 1H), 5.42 (d, J=17.3 Hz, 1H), 5.22-5.08 (m, 2H), 5.06-4.99 (m, 2H), 4.27 (d, J=6.0 Hz, 1H), 4.03 (d, J=4.7 Hz, 2H), 3.77 (s, 3H), 2.65 (br. s., 3H), 2.45-2.35 (m, 1H), 2.28 (s, 1H), 2.06-1.95 (m, 3H), 1.79-1.69 (m, 1H), 1.38 (br. s., 3H), 1.27 (s, 9H), 1.21 (d, J=6.0 Hz, 3H). LCMS (M+1)=685.4.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[CH:7](Br)[C:8]2[C:13]([C:14]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[CH:12][CH:11]=[C:10]([O:21][CH3:22])[CH:9]=2)=[O:5])[CH3:2].[CH2:24]([OH:26])[CH3:25]>[N+]([O-])([O-])=O.[Ag+]>[CH2:1]([O:3][C:4]([C:6]1[CH:7]([O:26][CH2:24][CH3:25])[C:8]2[C:13]([C:14]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[CH:12][CH:11]=[C:10]([O:21][CH3:22])[CH:9]=2)=[O:5])[CH3:2]
Reactant: CCO
Reactant: CCOC(=O)C1=C(c2ccccc2)c2ccc(OC)cc2C1Br
Agent: [Ag+]
Agent: O=[N+]([O-])[O-]
Product: CCOC(=O)C1=C(c2ccccc2)c2ccc(OC)cc2C1OCC
Temperature: 25 °C
Reaction time: 3.5 h
Yield: 52 %

Procedure:
1-Bromo-6-methoxy-3-phenyl-1H-indene-2-carboxylic acid ethyl ester (30 mg, 0.09 mmol) obtained in Example 18 was dissolved in ethanol (3 mL), silver nitrate (15.50 mg, 0.09 mmol) was added thereto, stirred for 3.5 hrs at RT, and filtered. The organic layer was separated, and concentrated under a reduced pressure. The resulting residue was purified by flash chromatography to obtain 16 mg of the titled compound (yield: 52%).
Reaction SMILES: [N:1]([CH:4]1[CH2:23][N:8]2[C:9]3[C:14]([C:15]([CH2:16][C:17]([O:19]CCC)=[O:18])=[C:7]2[CH2:6][CH2:5]1)=[CH:13][CH:12]=[CH:11][CH:10]=3)=[N+:2]=[N-:3].[CH2:24]([NH:30][S:31]([CH3:34])(=[O:33])=[O:32])[CH2:25][CH2:26][CH2:27][C:28]#[CH:29]>>[CH3:34][S:31]([NH:30][CH2:24][CH2:25][CH2:26][CH2:27][C:28]1[N:3]=[N:2][N:1]([CH:4]2[CH2:23][N:8]3[C:9]4[C:14]([C:15]([CH2:16][C:17]([OH:19])=[O:18])=[C:7]3[CH2:6][CH2:5]2)=[CH:13][CH:12]=[CH:11][CH:10]=4)[CH:29]=1)(=[O:33])=[O:32]
Reactant: C#CCCCCNS(C)(=O)=O
Reactant: CCCOC(=O)Cc1c2n(c3ccccc13)CC(N=[N+]=[N-])CC2
Product: CS(=O)(=O)NCCCCc1cn(C2CCc3c(CC(=O)O)c4ccccc4n3C2)nn1

Procedure:
The title compound was prepared using procedures described in EXAMPLE 1 from propyl (7-azido-6,7,8,9-tetrahydropyrido[1,2-α]indol-10-yl)acetate and N-hex-5-yn-1-ylmethanesulfonamide. MS (+ESI) m/z: 446.2.
Reaction SMILES: [N+:1]([C:4]1[CH:18]=[CH:17][C:7]([CH2:8][O:9][CH2:10][CH2:11][N:12]2[CH:16]=[CH:15][N:14]=[N:13]2)=[CH:6][CH:5]=1)([O-])=O.C1COCC1>CO.[Pt](=O)=O>[N:12]1([CH2:11][CH2:10][O:9][CH2:8][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:18][CH:17]=2)[CH:16]=[CH:15][N:14]=[N:13]1
Reactant: O=[N+]([O-])c1ccc(COCCn2ccnn2)cc1
Agent: O=[Pt]=O
Solvent: C1CCOC1
Solvent: CO
Product: Nc1ccc(COCCn2ccnn2)cc1
Yield: 95 %

Procedure:
1-[2-(4-Nitro-benzyloxy)-ethyl]-1H-[1,2,3]triazole (3.6 g, 14.5 mmol) and platinum dioxide (0.4 g) were suspended in methanol (30 ml) and THF (30 ml) and hydrogenated for 3 h at 42 mbar. After filtration and concentration 3 g (95%) 4-(2-[1,2,3]triazol-1-yl-ethoxymethyl)-phenylamine were obtained as beige solid.
Reaction SMILES: [F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[C:4]([C:11]2[N:12]=[C:13]([N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[C:14]3[S:19][C:18]([CH2:20][N:21]4[CH2:26][CH2:25]N5C[CH2:28][CH2:29][C@H:23]5[CH2:22]4)=[CH:17][C:15]=3[N:16]=2)[CH:3]=1.Cl.C(O[C:42]([N:44]1CC2(CCNCC2)C1)=O)(C)(C)C.C(O)(C(F)(F)F)=O.C(Cl)Cl>>[CH2:42]1[C:29]2([CH2:23][CH2:22][N:21]([CH2:20][C:18]3[S:19][C:14]4[C:13]([N:30]5[CH2:35][CH2:34][O:33][CH2:32][CH2:31]5)=[N:12][C:11]([C:4]5[CH:3]=[C:2]([F:1])[CH:10]=[C:9]6[C:5]=5[CH:6]=[CH:7][NH:8]6)=[N:16][C:15]=4[CH:17]=3)[CH2:26][CH2:25]2)[CH2:28][NH:44]1
Reactant: Fc1cc(-c2nc(N3CCOCC3)c3sc(CN4CCN5CCC[C@H]5C4)cc3n2)c2cc[nH]c2c1
Reactant: CC(C)(C)OC(=O)N1CC2(CCNCC2)C1
Agent: Cl
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Fc1cc(-c2nc(N3CCOCC3)c3sc(CN4CCC5(CC4)CNC5)cc3n2)c2cc[nH]c2c1

Procedure:
Prepared according to the method used in the preparation of 2-(6-fluoro-1H-indol-4-yl)-6-[(S)-1-(hexahydro-pyrrolo[1,2-a]pyrazin-2-yl)methyl]-4-morpholin-4-yl-thieno-[3,2-d]pyrimidine using 2,7-diaza-spiro[3.5]nonane-2-carboxylic acid tert-butyl ester hydrochloride in place of (S)-octahydro-pyrrolo[1,2-a]pyrazine, followed by BOC-deprotection using TFA:DCM (1:1). The title compound was obtained as a white solid (27 mg, 44%).
Reaction SMILES: [CH3:1][C:2](C)([O-])C.[K+].ICC.[CH3:10][O:11][N:12]([CH3:26])[C:13]([C:15]1[CH:23]=[C:22]2[C:18]([C:19]([CH2:24][CH3:25])=[N:20][NH:21]2)=[CH:17][CH:16]=1)=[O:14].C(OCC)(=O)C>C1COCC1>[CH3:10][O:11][N:12]([CH3:26])[C:13]([C:15]1[CH:23]=[C:22]2[C:18]([C:19]([CH2:24][CH3:25])=[N:20][N:21]2[CH2:1][CH3:2])=[CH:17][CH:16]=1)=[O:14]
Reactant: CC(C)(C)[O-]
Reactant: CCc1n[nH]c2cc(C(=O)N(C)OC)ccc12
Agent: [K+]
Solvent: CCI
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCc1nn(CC)c2cc(C(=O)N(C)OC)ccc12
Temperature: 25 °C
Reaction time: 16 h
Yield: 111.2 %

Procedure:
A mixture of potassium tert-butoxide (0.144 g, 1.28 mmol) and iodoethane (0.20 g, 1.28 mmol) in THF (1 mL) was added to a solution of 3-ethyl-1H-indazole-6-carboxylic acid methoxy-methyl-amide (0.20 g, 0.86 mmol) in THF (3 mL) and the resulting mixture stirred at room temperature for 16 hours. Ethyl acetate (30 mL) was then added and the product was extracted with 0.5 N HCl (10 mL). The aqueous layer was then re-extracted with ethyl acetate (30 mL). The organics were combined, dried, filtered and concentrated to afford 250 mg of 1,3-diethyl-1H-indazole-6-carboxylic acid methoxy-methyl-amide that was used without further purification.
Reaction SMILES: [CH2:1]([OH:5])[CH2:2][CH:3]=[CH2:4].N1C=CC=CC=1.[Si:12](Cl)([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13]>C(Cl)Cl>[Si:12]([O:5][CH2:1][CH2:2][CH:3]=[CH2:4])([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13]
Reactant: C=CCCO
Reactant: CC(C)(C)[Si](C)(C)Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: C=CCCO[Si](C)(C)C(C)(C)C
Temperature: 25 °C
Reaction time: 1 h
Yield: 56.2 %

Procedure:
Under a nitrogen atmosphere, to a cold (0° C.), stirring solution of 3-buten-1-ol (2.16 g, 30.0 mmol), pyridine (9 mL), and methylene chloride (30 mL) was added tert-butyldimethylsilyl chloride (4.53 g, 30.1 mmol) purchased from Aldrich Chemical Company. The ice-bath was removed and the mixture was allowed to stir 1 h at room temperature. The mixture, containing a white precipitate, was poured into water (60 mL) and shaken. The methylene chloride layer was separated from the aqueous layer, and the aqueous layer extracted with methylene chloride (30 mL). The two resulting organic extracts were combined, washed twice with water, dried (Na2SO4), filtered, and evaporated to give 8.94 g of crude product. Vacuum distillation afforded several fractions, the fraction with bp 80°-82° C. at 35 mm Hg was collected to give 3.14 g (56.3%) of product as an oil. 1H NMR (CDCl3): δ 5.86-5.73 (m, 1H), 5.08-4.98 (m, 2H), 3.64 (t, 2H), 2.29-2.22 (m, 2H), 0.87 (s, 9H), 0.03 (s, 6H).
Reaction SMILES: [C:1](Cl)(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16]CC.[NH2:21][C@H:22]([C:38]([N:40]1[CH2:48][CH2:47][CH2:46][C@H:41]1[C:42]([O:44][CH3:45])=[O:43])=[O:39])[CH2:23][CH2:24][CH2:25]CNC(OCC1C=CC=CC=1)=O.F[C:50](C(O)=O)(F)F>N(C(OCC1C=CC=CC=1)=O)[C@H](C(O)=O)C(C)C.N[C@H](C(N[C@H](C(N1CCC[C@H]1C(OC)=O)=O)CC(C)C)=O)CC(C)C>[NH:21]([C:1]([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][CH3:16])=[O:19])[C@H:22]([C:38]([N:40]1[CH2:48][CH2:47][CH2:46][C@H:41]1[C:42]([O:44][CH3:45])=[O:43])=[O:39])[CH2:23][CH:24]([CH3:25])[CH3:50]
Reactant: COC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CCCCNC(=O)OCc1ccccc1
Reactant: O=C(O)C(F)(F)F
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)Cl
Agent: CC(C)[C@H](NC(=O)OCc1ccccc1)C(=O)O
Agent: COC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(C)C
Product: CCCCCCCCCCCCCCCC(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)OC

Procedure:
Instead of oleoyl chloride in (b), (a) palmitoyl chloride, (b) stearoyl chloride and (c) linoleolyl chloride were used to obtain (a') palmitoyl-Leu-Pro-OMe (SUAM 1141), (b') stearoyl-Leu-Pro-OMe (SUAM 1142) and (c') linoleoyl-Leu-Pro-OMe (SUAM 1143), respectively. Further, instead of H-Leu-Pro-OMe in (b), (d) H-Val-Pro-OMe, (e) H-Ala-Pro-OMe (f) H-Leu-Leu-Pro-OMe, (g) H-Phe-Pro-OMe, (h) H-Met-Pro-OMe and (i) H-norLeu-Pro-OMe were used to obtain (d') oleoyl-Val-Pro-OMe (SUAM 1147), (e') oleoyl -Ala-Pro-OMe (SUAM 1076), (f') oleoyl-Leu-Leu-Pro-OMe (SUAM 1159), (g') oleoyl-Phe-Pro-OMe (SUAM) 1194), (h') oleoyl-Met-Pro-OMe (SUAM 1198) and (i') oleoyl-norLeu-Pro-OMe (SUAM 1164), as oils, respectively.
Reaction SMILES: [CH:1]([C:3]1[O:7][CH:6]=[C:5]([C:8]2[C:18]3[O:17][CH2:16][CH2:15][N:14]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:13][C:12]=3[CH:11]=[CH:10][CH:9]=2)[CH:4]=1)=O.O.NN.C(O)CO.[OH-].[K+]>O.CO>[CH3:1][C:3]1[O:7][CH:6]=[C:5]([C:8]2[C:18]3[O:17][CH2:16][CH2:15][N:14]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:13][C:12]=3[CH:11]=[CH:10][CH:9]=2)[CH:4]=1
Reactant: CC(C)(C)OC(=O)N1CCOc2c(cccc2-c2coc(C=O)c2)C1
Agent: NN
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CO
Solvent: OCCO
Product: Cc1cc(-c2cccc3c2OCCN(C(=O)OC(C)(C)C)C3)co1
Temperature: 70 °C
Reaction time: 0.17 h
Yield: 25 %

Procedure:
A mixture of tert-butyl 9-(5-formyl-3-furyl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (300 mg, 0.874 mmol), hydrazine monohydrate (0.100 ml, 2.06 mmol), ethylene glycol (6 ml) and methanol (4 ml) was stirred at 70° C. for 10 min. After cooling to room temperature, potassium hydroxide (147 mg, 2.62 mmol) was added, and the mixture was stirred at 100° C. for 1 hr. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1) to give the desired product (72.0 mg, 25.0%) as an oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([C:12](=O)[C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=1)[CH:7](C(O)=O)[CH2:6]2.[C:25]([C:31]([O:33][CH3:34])=[O:32])#[C:26][C:27]([O:29][CH3:30])=[O:28]>C(OC(=O)C)(=O)C>[CH3:30][O:29][C:27]([C:26]1[C:25]([C:31]([O:33][CH3:34])=[O:32])=[C:12]([C:13]2[CH:14]=[CH:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=2)[N:8]2[C:9]3[CH:10]=[CH:11][C:3]([O:2][CH3:1])=[CH:4][C:5]=3[CH2:6][C:7]=12)=[O:28]
Reactant: COc1ccc(C(=O)N2c3ccc(OC)cc3CC2C(=O)O)cc1
Reactant: COC(=O)C#CC(=O)OC
Solvent: CC(=O)OC(C)=O
Product: COC(=O)c1c(C(=O)OC)c(-c2ccc(OC)cc2)n2c1Cc1cc(OC)ccc1-2
Temperature: 120 °C

Procedure:
A mixture of 5-methoxy-1-(4′-methoxybenzoyl)-2,3-dihydro-1H-indole-2-carboxylic acid (4.24 g, 12.9 mmol) and dimethyl acetylenedicarboxylate (2.4 mL, 19.5 mmol) in acetic anhydride (24 mL) was heated for 4.5 hours at 120° C. until no gas eliminated. The dark solution was concentrated in vacuo to dryness and the solid residue was recrystallized from methanol to yield 6-methoxy-3-(4-methoxy-phenyl)-8H-3a-azacyclopenta[a]indene-1,2-dicarboxylic acid dimethyl ester, 3.75 g (71%): mp 240-242° C.; 1H NMR (DMSO-d6) δ 3.60 (3H, s, COOMe), 3.73 and 3.77 (each 3H, s, 2×OMe), 3.85 (3H, s, COOMe), 4.09 (2H, s, CH2), 6.55 (1H, d, J=8.8 Hz, ArH), 6.77 (1H, dd, J=2.6 Hz and J=8.8 Hz, ArH), 7.08 (2H, d, J=8.7 Hz, 2×ArH), 7.19 (1H, d, J=2.4 Hz, ArH), 7.42 (2H, d, J=8.7 Hz, 2×ArH). Anal. Calcd. for C23H21NO5: C, 67.84; H, 5.20; N, 3.44. Found: C, 67.83; H, 5.19; N, 3.39.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[NH:15][C:16](=[O:34])[C:17]1[CH:22]=[CH:21][C:20]([C:23]2[C:24]3[S:33][CH:32]=[CH:31][C:25]=3[N:26]=[C:27](SC)[N:28]=2)=[CH:19][CH:18]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:36]1C=CC=C(C(OO)=O)C=1.[S:46](S([O-])=O)([O-:49])(=O)=[O:47].[Na+].[Na+].C(OCC)(=O)C>CN(C=O)C>[C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[NH:15][C:16](=[O:34])[C:17]1[CH:22]=[CH:21][C:20]([C:23]2[C:24]3[S:33][CH:32]=[CH:31][C:25]=3[N:26]=[C:27]([S:46]([CH3:36])(=[O:49])=[O:47])[N:28]=2)=[CH:19][CH:18]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: CSc1nc(-c2ccc(C(=O)Nc3ccccc3NC(=O)OC(C)(C)C)cc2)c2sccc2n1
Reactant: O=S([O-])S(=O)(=O)[O-]
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)Nc1ccccc1NC(=O)c1ccc(-c2nc(S(C)(=O)=O)nc3ccsc23)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 57 %

Procedure:
To a cooled (0° C.) solution of N-(2-t-butoxycarbonylaminophenyl)-4-[2-(methylthio)thieno[3,2-d]pyrimidin-4-yl]benzamide (Method 55, 960 mg, 1.95 mg) in DMF (40 ml), was added meta-chloroperbenzoic acid (57%, 630 mg, 2.08 mmol) and the reaction mixture stirred, allowing warming to ambient temperature. After 3 hours a further portion of meta-chloroperbenzoic acid (70%, 589 mg, 2.40 mmol) was added and stirring continued for 2 hours. The reaction mixture was then carefully poured into aqueous sodium metabisulfite solution (0.25M, 100 ml), before addition of ethyl acetate (100 ml). The insoluble material was removed by filtration and dried in vacuo to yield the title compound (586 mg, 57%); NMR Spectrum: (DMSO-d6) 1.46 (s, 9H), 3.57 (s, 3H), 7.18 (t, 1H), 7.24 (t, 1H), 7.59 (m, 2H), 8.00 (d, 1H), 8.27 (d, 2H), 8.41 (d, 2H), 8.75 (s, 1H), 8.90 (d, 1H), 10.07 (s, 1H); Mass Spectrum: M+Na+ 547.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([Mg]Br)=[CH:4][CH:3]=1.[C:10]1(=O)[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:12][CH2:11]1>CCOCC>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:12]2[C:13]3[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH2:10][CH:11]=2)=[CH:4][CH:3]=1
Reactant: O=C1CCc2ccccc21
Reactant: Fc1ccc([Mg]Br)cc1
Solvent: CCOCC
Product: Fc1ccc(C2=CCc3ccccc32)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of solution of 4-fluorophenylmagnesium bromide (prepared from 6.43 ml of 4-fluorobromobenzene and 1.71 g of Mg in 50 ml of ether) at room temperature under argon was added dropwise over 40 minutes a solution of 1-indanone (6.61 g, 50 mmole) in dry ether (20 ml). After stirring at room temperature for 1 hour, the reaction was quenched by the dropwise addition of saturated NH4Cl solution (15 ml). The mixture was diluted with Et2O, washed with saturated NaCl solution, dried (MgSO4) and evaporated.
Reaction SMILES: C1([C:11]([O:13][C:14]([C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=[CH:18][CH:17]=2)=[O:15])=[O:12])C2C(=CC=CC=2)C=CC=1.[Br:26]Br>>[CH:18]1[CH:17]=[C:16]2[C:14]([O:13][C:11](=[O:12])[C:24]3=[C:25]2[C:20](=[CH:21][C:22]([Br:26])=[CH:23]3)[CH:19]=1)=[O:15]
Reactant: O=C(OC(=O)c1cccc2ccccc12)c1cccc2ccccc12
Reactant: BrBr
Product: O=C1OC(=O)c2cc(Br)cc3cccc1c23
Temperature: 50 °C
Reaction time: 4 h
Yield: 22.7 %

Procedure:
Naphthalic anhydride 20 (100 g, 505 mmol) was slurried in c-nitric acid (70%, 2.0 L) and heated to 50° C. Bromine (19.4 mL, 379 mmol) was added evenly over 10 min, and the resulting solution was held at 50° C. for 4 h before cooling to 0° C. The resulting solid was isolated by filtration and dried in vacuo to provide the titled compound 21 (23.8 g, 17%) as a white solid.
Reaction SMILES: C([C:4]1[C:12]2[CH:11]=[C:10]([B:13]([OH:15])[OH:14])[S:9][C:8]=2[CH:7]=[CH:6][CH:5]=1)(O)=O.S1C=CC2C=CC([C:25]([OH:27])=[O:26])=CC1=2>>[C:25]([C:6]1[CH:5]=[CH:4][C:12]2[CH:11]=[C:10]([B:13]([OH:14])[OH:15])[S:9][C:8]=2[CH:7]=1)([OH:27])=[O:26]
Reactant: O=C(O)c1cccc2sc(B(O)O)cc12
Reactant: O=C(O)c1ccc2ccsc2c1
Product: O=C(O)c1ccc2cc(B(O)O)sc2c1
Yield: 86 %

Procedure:
The title compound (120 g, 86%) is prepared essentially as described in the preparation of 4-carboxy-benzo[b]thiophen-2-boronic acid utilizing benzo[b]thiophene-6-carboxylic acid, ES/MS m/e 221 M−1).
Reaction SMILES: ClC1C(N)=C2C(C(OC)=CC=N2)=CC=1.[NH2:15][C:16]1[C:17]([C:26]([C:28]2[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=2)=O)=[CH:18][CH:19]=[C:20]2[C:25]=1[N:24]=[CH:23][CH:22]=[CH:21]2.[CH3:35][NH:36][S:37](Cl)(=[O:39])=[O:38].[BH4-].[Na+]>N1C=CC=CC=1>[CH3:35][N:36]1[S:37](=[O:39])(=[O:38])[NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][N:24]=3)[CH:19]=[CH:18][C:17]=2[CH:26]1[C:28]1[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=1
Reactant: CNS(=O)(=O)Cl
Reactant: Cc1ccc(C(=O)c2ccc3cccnc3c2N)cc1
Agent: COc1ccnc2c(N)c(Cl)ccc12
Agent: [BH4-]
Agent: [Na+]
Solvent: c1ccncc1
Product: Cc1ccc(C2c3ccc4cccnc4c3NS(=O)(=O)N2C)cc1
Yield: 5.1 %

Procedure:
In a similar fashion using route 27 general procedure (Intermediate 70), (8-amino-quinolin-7-yl)-p-tolyl-methanone (Intermediate 368) (180 mg, 0.69 mmol), N-methylsulamoyl chloride (Intermediate 213) (267 mg, 2.06 mmol) and NaBH4 (26 mg, 0.69 mmol) in pyridine (10 ml) gave the title compound (12 mg, 5%) after purification by column chromatography with heptane/EtOAc (80:20-50:50) as the eluent.
Reaction SMILES: [CH2:1]([CH:3]([CH2:6][CH2:7][CH2:8][CH3:9])[CH2:4][NH2:5])[CH3:2].[C:10]([C:14]1[CH:15]=[C:16]([CH:20]=[C:21]([C:24]([CH3:27])([CH3:26])[CH3:25])[C:22]=1[OH:23])[C:17](O)=[O:18])([CH3:13])([CH3:12])[CH3:11]>>[CH2:1]([CH:3]([CH2:6][CH2:7][CH2:8][CH3:9])[CH2:4][NH:5][C:17](=[O:18])[C:16]1[CH:20]=[C:21]([C:24]([CH3:25])([CH3:26])[CH3:27])[C:22]([OH:23])=[C:14]([C:10]([CH3:13])([CH3:12])[CH3:11])[CH:15]=1)[CH3:2]
Reactant: CCCCC(CC)CN
Reactant: CC(C)(C)c1cc(C(=O)O)cc(C(C)(C)C)c1O
Product: CCCCC(CC)CNC(=O)c1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1

Procedure:
In the manner of Example 7, 2-ethylhexylamine was reacted with 3,5-di-t-butyl-4-hydroxybenzoic acid to produce N-(2-ethylhexyl)-3,5-di-t-butyl-4-hydroxybenzamide; melting point 136°-140°C. When tested by the procedure of Example 2, this compound lasted 1000 hours, about 3.3 times as long as the control.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH3:14])[C:5]([C:8]2[CH2:9][CH2:10][NH:11][CH2:12][CH:13]=2)=[N:6][CH:7]=1.[CH3:15][CH:16]1[C:20](=O)[CH2:19][CH2:18][O:17]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClCCl>[Br:1][C:2]1[CH:3]=[C:4]([CH3:14])[C:5]([C:8]2[CH2:9][CH2:10][N:11]([C@H:20]3[CH2:19][CH2:18][O:17][C@H:16]3[CH3:15])[CH2:12][CH:13]=2)=[N:6][CH:7]=1.[Br:1][C:2]1[CH:3]=[C:4]([CH3:14])[C:5]([C:8]2[CH2:9][CH2:10][N:11]([C@@H:20]3[CH2:19][CH2:18][O:17][C@H:16]3[CH3:15])[CH2:12][CH:13]=2)=[N:6][CH:7]=1
Reactant: CC1OCCC1=O
Reactant: Cc1cc(Br)cnc1C1=CCNCC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Product: Cc1cc(Br)cnc1C1=CCN([C@@H]2CCO[C@H]2C)CC1
Product: Cc1cc(Br)cnc1C1=CCN([C@H]2CCO[C@H]2C)CC1
Temperature: 25 °C
Reaction time: 6 h

Procedure:
To a solution of 5-bromo-3-methyl-1′,2′,3′,6′-tetrahydro-2,4′-bipyridine (2.26 g) described in Reference Example 109 (2) and 2-methyltetrahydrofuran-3-one (1.1 ml) in dichloromethane (25 ml) was added sodium triacetoxyborohydride (2.77 g), and stirred at room temperature for 6 hours. To the reaction solution was added 1 N aqueous solution of sodium hydroxide, and extracted with chloroform. The obtained organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated in vacuo. The obtained residue was purified with silica gel chromatography (n-hexane/ethyl acetate) to give cis-4-(5-bromo-3-methyl-pyridin-2-yl)-1-(2-methyltetrahydrofuran-3-yl)-1,2,3,6-tetrahydropyridine (2.43 g) and trans-4-(5-bromo-3-methylpyridin-2-yl)-1-(2-methyltetrahydrofuran-3-yl)-1,2,3,6-tetrahydropyridine (193 mg) as brown oils respectively. MS (ESI) m/z: 337, 339 (M+H)+.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[CH:5]2.[C:11]1([N:17]=[CH:18]OCC)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>C(O)C>[OH:1][C:2]1[C:3]([CH:18]=[N:17][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[CH:5]2
Reactant: CCOC=Nc1ccccc1
Reactant: Oc1ccc2[nH]ncc2c1
Solvent: CCO
Product: Oc1ccc2[nH]ncc2c1C=Nc1ccccc1
Temperature: 175 °C
Reaction time: 0.5 h
Yield: 63.5 %

Procedure:
A round bottomed flask containing a mixture of 5-hydroxy-1H-indazole (28.5 g) and ethyl N-phenylformimidate (35 g) was submerged rapidly in an oil bath pre-heated to 175° C. and the mixture stirred at 160-180° C. for 30 minutes, the ethanol produced in the reaction being removed by distillation. The cooled mixture was then treated with boiling methanol (500 ml) and the resultant brown solid collected by filtration, washed with methanol (100 ml) and dried to give 5-hydroxy-4-(N-phenyliminomethyl)-1H-indazole (32 g) as a yellow solid. The solid was dissolved in hydrochloric acid (5 M; 500 ml) and heated at 50-60° C. with stirring for 2 hours. The mixture was diluted with water (500 ml) and extracted with ethyl acetate (2×500 ml). The combined extracts were washed with water (500 ml), dried over magnesium sulphate and the solvent evaporated under reduced pressure to give 5-hydroxy-1H-indazole-4-carboxaldehyde (15.48 g) as a yellow solid.