Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CCN(C(C)C)C(C)C.F[C:11]1[C:16]([N+:17]([O-:19])=[O:18])=[CH:15][C:14]([NH:20][C:21]2[N:26]=[C:25]([C:27]3[CH:28]=[N:29][N:30]4[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=34)[CH:24]=[CH:23][N:22]=2)=[C:13]([O:36][CH3:37])[CH:12]=1.[CH3:38][N:39]1[CH2:43][C@@H:42]2[NH:44][CH2:45][CH2:46][C@@H:41]2[CH2:40]1>FC(F)(F)CO>[CH3:38][N:39]1[CH2:40][C@@H:41]2[C@@H:42]([N:44]([C:11]3[C:16]([N+:17]([O-:19])=[O:18])=[CH:15][C:14]([NH:20][C:21]4[N:26]=[C:25]([C:27]5[CH:28]=[N:29][N:30]6[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=56)[CH:24]=[CH:23][N:22]=4)=[C:13]([O:36][CH3:37])[CH:12]=3)[CH2:45][CH2:46]2)[CH2:43]1
Reactant: CN1C[C@H]2CCN[C@H]2C1
Reactant: COc1cc(F)c([N+](=O)[O-])cc1Nc1nccc(-c2cnn3ccccc23)n1
Solvent: CCN(C(C)C)C(C)C
Solvent: OCC(F)(F)F
Product: COc1cc(N2CC[C@@H]3CN(C)C[C@@H]32)c([N+](=O)[O-])cc1Nc1nccc(-c2cnn3ccccc23)n1
Temperature: 140 °C
Yield: 51.5 %

Procedure:
DIPEA (0.343 mL, 1.97 mmol) was added to a suspension of N-(4-fluoro-2-methoxy-5-s nitrophenyl)-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine (Intermediate 155, 300 mg, 0.79 mmol) and (3aR,6aR)-5-methyl-2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[3,4-b]pyrrole (Intermediate 37, 109 mg, 0.87 mmol) in 2,2,2-trifluoroethanol (5 mL) and the mixture was heated in a microwave at 140° C. for 1 h. After cooling, the mixture was part-purified by ion exchange chromatography, using an SCX column and eluting with 7M methanolic ammonia. Appropriate fractions were then concentrated in vacuo onto silica. Further purification by FCC, eluting with 0-4% 7N methanolic ammonia in CH2Cl2 gave the title compound (198 mg, 52%) as a slightly impure orange/red solid which was used without further purification; 1H NMR (CDCl3): 1.89 (1H, dd), 2.06-2.18 (1H, m), 2.21 (3H, s), 2.31 (1H, dd), 2.47 (2H, ddd), 2.65 (1H, t), 2.99-3.10 (1H, m), 3.26 (1H, t), 3.51-3.60 (1H, m), 3.98 (3H, s), 4.39-4.46 (1H, m), 6.46 (1H, s), 6.93 (1H, td), 7.04 (1H, d), 7.38 (1H, s), 7.43 (1H, ddd), 8.36 (1H, d), 8.46 (1H, s), 8.52 (1H, m), 8.58 (1H, m), 8.98 (1H, s); m/z: ES+ MH+ 487.15.
Reaction SMILES: C([O:4][CH2:5][C:6]([NH:36]C(=O)C)([CH2:31][O:32]C(=O)C)[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][C:18]([S:21][C:22]3[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=3)=[CH:17][C:16]=2[F:29])=[CH:11][C:10]=1[Cl:30])(=O)C.Cl>C(O)C>[NH2:36][C:6]([CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][C:18]([S:21][C:22]3[CH:23]=[CH:24][C:25]([CH3:28])=[CH:26][CH:27]=3)=[CH:17][C:16]=2[F:29])=[CH:11][C:10]=1[Cl:30])([CH2:31][OH:32])[CH2:5][OH:4]
Reactant: CC(=O)NC(CCc1ccc(-c2ccc(Sc3ccc(C)cc3)cc2F)cc1Cl)(COC(C)=O)COC(C)=O
Agent: Cl
Solvent: CCO
Product: Cc1ccc(Sc2ccc(-c3ccc(CCC(N)(CO)CO)c(Cl)c3)c(F)c2)cc1
Temperature: 75 °C
Reaction time: 3 h
Yield: 56.7 %

Procedure:
N-[1,1-Bis(acetoxymethyl)-3-[3-chloro-2′-fluoro-4′-(4-methylphenylthio)biphenyl-4-yl]propyl]acetamide (0.24 g) was dissolved in ethanol (4 mL), concentrated hydrochloric acid (2 mL) was added, and the mixture was stirred at 75° C. for 3 hr. The reaction mixture was concentrated, aqueous potassium carbonate solution was added to the residue, and the precipitated crystals were collected by filtration. The crude crystals were purified by preparative HPLC to give the title compound (106 mg) as white crystals.
Reaction SMILES: [NH2:1][CH2:2][C:3]([N:5]([C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[C:9]([CH2:14][O:15][C:16]2[C:24]3[N:23]=[C:22]([O:25][CH3:26])[N:21]([CH2:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=4)[C:20]=3[CH:19]=[CH:18][CH:17]=2)[C:8]=1[Cl:34])[CH3:6])=[O:4].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:59][NH:60][C:61]([CH:63]1[CH2:68][CH2:67][CH2:66][N:65]([CH2:69][C:70](O)=[O:71])[CH2:64]1)=[O:62].C(N(C(C)C)CC)(C)C>CN(C=O)C.C(OCC)(=O)C>[Cl:34][C:8]1[C:9]([CH2:14][O:15][C:16]2[C:24]3[N:23]=[C:22]([O:25][CH3:26])[N:21]([CH2:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=4)[C:20]=3[CH:19]=[CH:18][CH:17]=2)=[C:10]([Cl:13])[CH:11]=[CH:12][C:7]=1[N:5]([CH3:6])[C:3](=[O:4])[CH2:2][NH:1][C:70](=[O:71])[CH2:69][N:65]1[CH2:66][CH2:67][CH2:68][CH:63]([C:61]([NH:60][CH3:59])=[O:62])[CH2:64]1
Reactant: COc1nc2c(OCc3c(Cl)ccc(N(C)C(=O)CN)c3Cl)cccc2n1Cc1ccccn1
Reactant: CNC(=O)C1CCCN(CC(=O)O)C1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: CNC(=O)C1CCCN(CC(=O)NCC(=O)N(C)c2ccc(Cl)c(COc3cccc4c3nc(OC)n4Cc3ccccn3)c2Cl)C1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of 2-amino-N-(2,4-dichloro-3-(((2-methoxy-1-(pyridin-2-ylmethyl)-1H-benzo[d]imidazol-4-yl)oxy)methyl)phenyl)-N-methylacetamide (0.45 g, 0.9 mmol) in anhydrous DMF (10 ml) was treated with HBTU (0.48 g, 1.2 mmol), 2-(3-(methylcarbamoyl)piperidin-1-yl)acetic acid (0.20 g, 0.99 mmol) and diisopropylethyl amine (0.47 mL, 2.7 mmol) with stirring at room temperature overnight. To the reaction was added ethyl acetate (100 mL) and the mixture was washed with aqueous saturated sodium bicarbonate (100 mL×3). The organic layer was dried over magnesium sulfate, filtered and evaporated to a sticky yellow residue, 0.63 g that was purified by chromatography (silica gel, dichloromethane and methanol gradient) to afford 1-(2-(2-((2,4-dichloro-3-((2-methoxy-1-(pyridin-2-ylmethyl)-1H-benzo[d]imidazol-4-yloxy)methyl)phenyl)(methyl)amino)-2-oxoethylamino)-2-oxoethyl)-N-methylpiperidine-3-carboxamide (35) as a white solid, 0.17 g (28%), that was pure by LC/MS (+APCI) m/z 682 (M++1), 1HNMR (400 MHz, CDCl3) δ 8.60 (m, 1H), 7.60 (m, 2H), 7.50 (m, 1H), 7.30 (m, 1H), 7.35 (m, 1H), 7.19 (m, 1H), 7.04 (m, 1H), 6.92 (m, 1H), 6.81 (m, 2H), 6.70 (broad m, 1H), 5.67 (s, 2H), 5.29 (s, 2H), 4.21 (two s, 3H), 4.1 to 1.4 (many multiplets, 19H). 13CNMR (100 MHz, CDCl3) δ 174.4, 170.5, 168.8, 156.8, 156.1, 149.6, 149.0, 138.4, 138.2, 137.0, 136.5, 135.8, 135.3, 130.3, 122.6, 121.7, 120.8, 107.3, 103.1, 67.0, 61.6, 57.5, 56.5, 56.2, 54.3, 53.4, 47.7, 45.4, 41.3, 36.0, 30.9, 26.3, 26.1, 24.5. Anal. Calcd for C33H37Cl2N6O5+0.57CH2Cl2: C, 55.16; H, 5.26; N, 13.41. Found: C, 55.18; H, 5.14; N, 13.35.
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[C:8]([C:10]2[O:11][CH:12]=[CH:13][CH:14]=2)[C:5]([C:6]#[N:7])=[C:4](S(C)=O)[N:3]=1.[N:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[CH2:24][NH2:25]>COCCOC>[NH2:1][C:2]1[CH:9]=[C:8]([C:10]2[O:11][CH:12]=[CH:13][CH:14]=2)[C:5]([C:6]#[N:7])=[C:4]([NH:25][CH2:24][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][N:18]=2)[N:3]=1
Reactant: CS(=O)c1nc(N)cc(-c2ccco2)c1C#N
Reactant: NCc1ccccn1
Solvent: COCCOC
Product: N#Cc1c(-c2ccco2)cc(N)nc1NCc1ccccn1
Temperature: 100 °C
Yield: 34 %

Procedure:
To a stirred suspension of 250 mg (1.01 mmol) 6-amino-4-furan-2-yl-2-methanesulfinyl-nicotinonitrile in 10 ml DME was added 0.41 ml (4.04 mmol) 2-picolylamine and the mixture heated at 100° C. for 16 hours. The reaction mixture was then cooled to room temperature and partitioned between water and dichloromethane. The organic phase was dried over sodium sulfate and concentrated in vacuo. Chromatography (ethyl acetate) followed by trituration in ether afforded 100 mg (34%) 6-amino-4-furan-2-yl-2-[(pyridin-2-ylmethyl)-amino]-nicotinonitrile as an off-white crystalline solid. ES-MS m/e (%): 292 (M+H+, 100).
Reaction SMILES: CN(C)C=O.[N-:6]=[N+:7]=[N-:8].[Na+].[C:10]([O:13][C@@H:14]1[O:31][C@H:30]([CH2:32]S(C)(=O)=O)[C@@H:25]([O:26][C:27](=[O:29])[CH3:28])[C@H:20]([O:21][C:22](=[O:24])[CH3:23])[C@H:15]1[O:16][C:17](=[O:19])[CH3:18])(=[O:12])[CH3:11]>C(OCC)(=O)C>[C:10]([O:13][C@@H:14]1[O:31][C@H:30]([CH2:32][N:6]=[N+:7]=[N-:8])[C@@H:25]([O:26][C:27](=[O:29])[CH3:28])[C@H:20]([O:21][C:22](=[O:24])[CH3:23])[C@H:15]1[O:16][C:17](=[O:19])[CH3:18])(=[O:12])[CH3:11]
Reactant: CC(=O)O[C@@H]1O[C@H](CS(C)(=O)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC(=O)O[C@@H]1O[C@H](CN=[N+]=[N-])[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O
Temperature: 70 °C
Yield: 39.4 %

Procedure:
A 100 mL round bottom flask was charged with 40 mL anhydrous dimethylformamide, sodium azide (2.19 g, 33.6 mmol), and crude 1,2,3,4-tetra-O-acetyl-6-deoxy-6-methanesulfonyl-β-D-glucopyranose (1.9374 g, 4.54 mmol). The resulting homogeneous solution was heated to 70° C. and allowed to react for 10 hours. The reaction was then diluted with 200 mL of ethyl acetate and washed with copious amounts of water. The organic layer was dried over magnesium sulfate, filtered and the solvent removed in vacuo. The resulting brown solid was purified by column chromatography over silica gel to yield 668.3 mg of the title compound (39.5%). MS (FAB) calculated for C14H19N3O9 (M—OCOCH3) 314.1, found 314.1.
Reaction SMILES: [C:1]([O:5][C:6](=[O:12])[C:7]([CH3:11])([CH3:10])[CH2:8][OH:9])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[N+](C1C=CC([O:24][C:25]([N:27]2[C:36]3[C:31](=[CH:32][C:33]([C:37]([F:40])([F:39])[F:38])=[CH:34][CH:35]=3)[C@@H:30]([NH:41][C:42]3[CH:47]=[CH:46][C:45]([N:48]4[CH2:53][CH2:52][O:51][CH2:50][CH2:49]4)=[CH:44][N:43]=3)[CH2:29][C@H:28]2[CH2:54][CH3:55])=O)=CC=1)([O-])=O.C(=O)([O-])O.[Na+]>O1CCCC1.C(OCC)(=O)C>[C:1]([O:5][C:6]([C:7]([CH3:11])([CH3:10])[CH2:8][O:9][C:25]([N:27]1[C:36]2[C:31](=[CH:32][C:33]([C:37]([F:40])([F:38])[F:39])=[CH:34][CH:35]=2)[C@@H:30]([NH:41][C:42]2[CH:47]=[CH:46][C:45]([N:48]3[CH2:49][CH2:50][O:51][CH2:52][CH2:53]3)=[CH:44][N:43]=2)[CH2:29][C@H:28]1[CH2:54][CH3:55])=[O:24])=[O:12])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC[C@@H]1C[C@H](Nc2ccc(N3CCOCC3)cn2)c2cc(C(F)(F)F)ccc2N1C(=O)Oc1ccc([N+](=O)[O-])cc1
Reactant: CC(C)(C)OC(=O)C(C)(C)CO
Agent: O=C([O-])O
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC[C@@H]1C[C@H](Nc2ccc(N3CCOCC3)cn2)c2cc(C(F)(F)F)ccc2N1C(=O)OCC(C)(C)C(=O)OC(C)(C)C
Temperature: 50 °C
Reaction time: 2 h
Yield: 71.3 %

Procedure:
3-Hydroxy-2,2-dimethyl-propionic acid tert-butyl ester (137 mg) and sodium hydride (60%; 32 mg) were added to a solution of the compound obtained in Example 9 (1) (300 mg) dissolved in tetrahydrofuran (5 ml) and stirred at 50° C. for 2 hours. The reaction mixture was cooled to room temperature, a saturated sodium hydrogen carbonate aq. solution and ethyl acetate were added and the organic layer was separated, washed with a saturated brine, dried over magnesium sulfate and concentrated in vacuo. The resulting residue was purified by column chromatography (silica gel; hexane:ethyl acetate=7:3→2:3) to give the titled compound (227 mg). MS (m/z):607 [M+H]+.
Reaction SMILES: [C:1]([O:4][CH2:5][C:6]1[C:7]([N:21]2[CH2:33][CH2:32][N:24]3[C:25]4[CH2:26][CH2:27][CH2:28][CH2:29][C:30]=4[CH:31]=[C:23]3[C:22]2=[O:34])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16](Br)[C:15](=[O:19])[N:14]([CH3:20])[CH:13]=1)(=[O:3])[CH3:2].[CH3:35][N:36]1[CH:41]([CH3:42])[CH2:40][N:39]2[N:43]=[C:44]([NH2:46])[CH:45]=[C:38]2[CH2:37]1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[C:1]([O:4][CH2:5][C:6]1[C:7]([N:21]2[CH2:33][CH2:32][N:24]3[C:25]4[CH2:26][CH2:27][CH2:28][CH2:29][C:30]=4[CH:31]=[C:23]3[C:22]2=[O:34])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:46][C:44]2[CH:45]=[C:38]3[CH2:37][N:36]([CH3:35])[CH:41]([CH3:42])[CH2:40][N:39]3[N:43]=2)[C:15](=[O:19])[N:14]([CH3:20])[CH:13]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)OCc1c(-c2cc(Br)c(=O)n(C)c2)ccnc1N1CCn2c(cc3c2CCCC3)C1=O
Reactant: CC1Cn2nc(N)cc2CN1C
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Product: CC(=O)OCc1c(-c2cc(Nc3cc4n(n3)CC(C)N(C)C4)c(=O)n(C)c2)ccnc1N1CCn2c(cc3c2CCCC3)C1=O
Temperature: 25 °C
Yield: 13.1 %

Procedure:
A 50-mL round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with (4-(5-bromo-1-methyl-6-oxo-1,6-di-hydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-3-yl)methyl acetate 217a (525 mg, 1.0 mmol), 250e (166 mg, 1.0 mmol), cesium carbonate (652 mg, 2.0 mmol), and 1,4-dioxane (10 mL). After bubbling nitrogen through the suspension for 30 minutes, xantphos (116 mg, 0.20 mmol) and tris(dibenzylideneacetone)dipalladium(0) (92 mg, 0.10 mmol) were added. The system was subjected to three cycles of vacuum/argon flush and heated at reflux for 5 h. It was then cooled to room temperature and filtered. The solid was washed with dichloromethane (2×30 mL) and the combined filtrate was concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with dichloromethane/methanol (80:1 to 30:1) to afford 250f (80 mg, 13%) as yellow solid. MS-ESI: [M+H]+ 611.4
Reaction SMILES: [NH2:1][C:2]12[CH2:12][CH2:11][CH:8]([CH:9]=[CH:10]1)[CH:7]1[CH:3]2[CH2:4][N:5](CC2C=CC=CC=2)[CH2:6]1>C(O)C.[Pd]>[NH2:1][C:2]12[CH2:10][CH2:9][CH:8]([CH2:11][CH2:12]1)[CH:7]1[CH:3]2[CH2:4][NH:5][CH2:6]1
Reactant: NC12C=CC(CC1)C1CN(Cc3ccccc3)CC12
Agent: [Pd]
Solvent: CCO
Product: NC12CCC(CC1)C1CNCC12

Procedure:
8.3 g (32.6 mmol) of 1-amino-4-benzyl-4-azatricyclo[5.2.2.02,6 ]undec-8-ene are hydrogenated in 100 ml of ethanol over 1 g of palladium/active charcoal at 100° C./100 bar. The catalyst is filtered off with suction, the filtrate is concentrated and the residue is distilled.
Reaction SMILES: [CH:1]1([CH2:4][NH:5][CH2:6][C:7]2[CH:8]=[C:9](C3C=C4C(=C(C(N)=O)C=3)NC=C4C3CCN(S(CC)(=O)=O)CC3)[CH:10]=[N:11][CH:12]=2)CC1.[CH3:36][C:37]1([CH3:52])[C:41]([CH3:43])([CH3:42])[O:40][B:39](C2C=C(C=O)C=NC=2)[O:38]1.C(N)C.C1COCC1.[BH3-]C#N.[Na+]>>[CH2:4]([NH:5][CH2:6][C:7]1[CH:12]=[N:11][CH:10]=[C:9]([B:39]2[O:40][C:41]([CH3:43])([CH3:42])[C:37]([CH3:52])([CH3:36])[O:38]2)[CH:8]=1)[CH3:1]
Reactant: CC1(C)OB(c2cncc(C=O)c2)OC1(C)C
Reactant: CCS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(-c4cncc(CNCC5CC5)c4)cc23)CC1
Agent: CCN
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: C1CCOC1
Product: CCNCc1cncc(B2OC(C)(C)C(C)(C)O2)c1

Procedure:
Following the general procedure of 5-(5-{[(cyclopropylmethyl)amino]methyl}-3-pyridinyl)-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide, 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinecarbaldehyde (30 mg, 0.129 mmol), a 2 M solution of ethylamine in THF (0.065 mL, 0.129 mmol), and NaCNBH3 (16 mg, 0.258 mmol) were reacted to give 19 mg of crude ethyl{[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinyl]methyl}amine. The crude ethyl{[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinyl]methyl}amine was then reacted with 5-bromo-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide (30 mg, 0.0723 mmol), potassium carbonate (60 mg, 0.434 mmol), and chloro-2-(dimethylaminormethyl)-ferrocen-1-yl-(dinorbornylphosphine)palladium(II) (4.4 mg, 0.00723 mmol) to give 12.3 mg of the title compound (36%).
Reaction SMILES: NC1C2=C3N(C(C)CC2)C=C(C(O)=O)C(=O)C3=CC=1.[CH3:20][CH:21]1[N:30]2[C:25]3[C:26](=[CH:35][CH:36]=[C:37]([N:38]4[CH:42]=[CH:41][CH:40]=[CH:39]4)[C:24]=3[CH2:23][CH2:22]1)[C:27](=[O:34])[C:28]([C:31]([OH:33])=[O:32])=[CH:29]2.[H][H]>FC(F)(F)C(O)=O.[Rh]>[CH3:20][CH:21]1[N:30]2[C:25]3[C:26](=[CH:35][CH:36]=[C:37]([N:38]4[CH2:42][CH2:41][CH2:40][CH2:39]4)[C:24]=3[CH2:23][CH2:22]1)[C:27](=[O:34])[C:28]([C:31]([OH:33])=[O:32])=[CH:29]2
Reactant: CC1CCc2c(-n3cccc3)ccc3c(=O)c(C(=O)O)cn1c23
Reactant: [H][H]
Agent: [Rh]
Agent: CC1CCc2c(N)ccc3c(=O)c(C(=O)O)cn1c23
Solvent: O=C(O)C(F)(F)F
Product: CC1CCc2c(N3CCCC3)ccc3c(=O)c(C(=O)O)cn1c23

Procedure:
Using the method of Example 5, 3.0 g of 8-amino-6,7-dihydro-5-methyl-1-oxo-1H,5H-benzo[ij]quinolizine-2-carboxylic acid was converted to 6,7-dihydro-5-methyl-1-oxo-8-(1-pyrryl)-1H,5H-benzo[ij]quinolizine-2-carboxylic acid. The crude product was dissolved in 50 ml of trifluoroacetic acid and 2 g of rhodium on alumina was added. The mixture was hydrogenated at 20° C. for 18 hours at 50 psi of hydrogen gas. The mixture was filtered, evaporated to dryness and dissolved in 10 percent sodium hydroxide solution. The solution was acidified with glacial acetic acid. The product was recrystallized from N,N-dimethyformamide to provide tan crystals of 6,7-dihydro-5-methyl-1-oxo-8-(1-pyrrolidyl)-1H,5H-benzo[ij]quinolizine-2-carboxylicacid, m.p. 170°-174° C. Nuclear magnetic resonance analysis showed water and N,N-dimethyl formamide present in the solid. Analysis: Calculated for C18H20N2O3.1/10(CH3)2NCHO.1/2H2O: %C, 66.8; %H, 6.6; %N, 9.2; Found: %C, 66.7; %H, 6.2; %N, 9.2.
Reaction SMILES: Cl[CH:2]([C:4]1[N:9]=[C:8]([O:10][CH3:11])[CH:7]=[C:6]([O:12][CH3:13])[N:5]=1)[CH3:3].[Na].[CH3:15][SH:16].O>CN(C=O)C>[CH3:15][S:16][CH:2]([C:4]1[N:9]=[C:8]([O:10][CH3:11])[CH:7]=[C:6]([O:12][CH3:13])[N:5]=1)[CH3:3]
Reactant: CS
Reactant: COc1cc(OC)nc(C(C)Cl)n1
Agent: [Na]
Solvent: CN(C)C=O
Solvent: O
Product: COc1cc(OC)nc(C(C)SC)n1
Temperature: 50 °C
Reaction time: 1 h
Yield: 90.3 %

Procedure:
2-(1-Chloroethyl)-4,6-dimethoxypyrimidine 15.5 g (76.5 mmol) was dissolved in DMF 200 ml and sodium salt of methylmercaptan 5.4 g (76.5 mmol) was added thereto at room temperature. The solution was stirred at 50° C. for 1 hour. The reaction solution was poured into water and extracted with ethyl acetate. The solvent was distilled off and the residue was purified with column chromatography (hexane/ethyl acetate=5/1) to obtain 2-(1-methylthioethyl)-4,6-dimethoxypyrimidine 14.8 g (90%).
Reaction SMILES: [Si:1]([O:8][C:9]1[CH:16]=[CH:15][C:12]([CH2:13]O)=[CH:11][CH:10]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].S(Cl)([Cl:19])=O>>[Si:1]([O:8][C:9]1[CH:16]=[CH:15][C:12]([CH2:13][Cl:19])=[CH:11][CH:10]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: O=S(Cl)Cl
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc(CO)cc1
Product: CC(C)(C)[Si](C)(C)Oc1ccc(CCl)cc1

Procedure:
A mixture composed of 286 mg of 4-(tert-butyldimethylsilyloxy)benzyl alcohol and 1.75 ml of thionyl chloride was heated under reflux for 1 hour. After the thionyl chloride was distilled off from the reaction mixture under reduced pressure, its azeotropic distillation with toluene was carried out three times to remove any thionyl chloride. Thus, there was obtained 4-(tert-butyldimethylsilyloxy)benzyl chloride.
Reaction SMILES: C([Li])CCC.[CH3:6][P:7](=[O:12])([O:10][CH3:11])[O:8][CH3:9].O1CCCC1.[CH2:18]([C@H:20]1[CH2:25][CH2:24][C@H:23]([C:26](OCC)=[O:27])[CH2:22][CH2:21]1)[CH3:19]>CCCCCC>[O:27]=[C:26]([C@H:23]1[CH2:24][CH2:25][C@H:20]([CH2:18][CH3:19])[CH2:21][CH2:22]1)[CH2:6][P:7](=[O:12])([O:10][CH3:11])[O:8][CH3:9]
Reactant: CCOC(=O)[C@H]1CC[C@H](CC)CC1
Reactant: COP(C)(=O)OC
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CC[C@H]1CC[C@H](C(=O)CP(=O)(OC)OC)CC1
Temperature: -70 °C
Reaction time: 1 h

Procedure:
Under an atmosphere of nitrogen, 47 ml. of a 1.25M solution of n-butyllithium in n-hexane were added dropwise to a solution of 7.64 g. of dimethyl methylphosphonate in 120 ml. of tetrahydrofuran at -70° C. After one hour of stirring at -70° C., a solution of 5.63 g. of ethyl trans-4-ethylcyclohexanecarboxylate [c.f. N. L. Allinger and L. A. Freiberg, J. Org. Chem., 31, 894, (1966)] in 30 ml. of tetrahydrofuran was added dropwise at -70° C., and the mixture was stirred at the same temperature for one hour and further stirred at -5° C., for one hour. The reaction mixture was then acidified with acetic acid and concentration under reduced pressure. The residue was diluted with diethyl ether, washed with water and an aqueous solution of sodium chloride, dried over magnesium sulphate and concentrated under reduced pressure. The residue was purified by distillation to give 5.0 g. of the title compound having the following physical characteristics:-
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([Cl:11])[CH:10]=1)[C:5](Cl)=[O:6].[Cl:12][C:13]1[CH:21]=[C:20]2[C:16]([C:17]([NH2:22])=[N:18][NH:19]2)=[CH:15][CH:14]=1>N1C=CC=CC=1>[Cl:12][C:13]1[CH:21]=[C:20]2[C:16]([C:17]([NH:22][C:5](=[O:6])[C:4]3[CH:3]=[C:2]([Cl:1])[CH:10]=[C:9]([Cl:11])[CH:8]=3)=[N:18][NH:19]2)=[CH:15][CH:14]=1
Reactant: O=C(Cl)c1cc(Cl)cc(Cl)c1
Reactant: Nc1n[nH]c2cc(Cl)ccc12
Solvent: c1ccncc1
Product: O=C(Nc1n[nH]c2cc(Cl)ccc12)c1cc(Cl)cc(Cl)c1
Temperature: 3 °C
Reaction time: 0.17 h

Procedure:
0.83 cm3 of 3,5-dichlorobenzoyl chloride is added to 1 g of 6-chloro-1H-indazole-3-amine in 15 cm3 of pyridine, after cooling in an ice bath to about 3° C., and the mixture is then stirred for 10 minutes at this temperature and is allowed to return to room temperature over 18 hours. The reaction medium is then concentrated to dryness under reduced pressure (2 kPa; 50° C.) and the residue is taken up in 25 cm3 of ethyl acetate and 25 cm3 of water. The precipitate formed is filtered off and, after drying (90 Pa; 50° C.), 700 mg of N-[6-chloro-1H-indazol-3-yl]-3,5-dichlorobenzamide are obtained in the form of a white solid melting at about 240° C.
Reaction SMILES: [CH:1]1([C:4]2[N:9]3[N:10]=[CH:11][C:12](I)=[C:8]3[CH:7]=[C:6]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=3)[CH:5]=2)[CH2:3][CH2:2]1.[C:24]([C:26]1[CH:27]=[CH:28][C:29]([NH2:32])=[N:30][CH:31]=1)#[CH:25]>>[CH:1]1([C:4]2[N:9]3[N:10]=[CH:11][C:12]([C:25]#[C:24][C:26]4[CH:27]=[CH:28][C:29]([NH2:32])=[N:30][CH:31]=4)=[C:8]3[CH:7]=[C:6]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=3)[CH:5]=2)[CH2:3][CH2:2]1
Reactant: FC(F)(F)c1ccc(-c2cc(C3CC3)n3ncc(I)c3c2)cc1
Reactant: C#Cc1ccc(N)nc1
Product: Nc1ccc(C#Cc2cnn3c(C4CC4)cc(-c4ccc(C(F)(F)F)cc4)cc23)cn1

Procedure:
The title compound was prepared from 7-cyclopropyl-3-iodo-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyridine (example C.28 step 7) (204 mg, 0.48 mmol) and 5-ethynyl-pyridin-2-ylamine (example D.1) (101 mg, 0.85 mmol) according to general procedure II. Obtained as a yellow solid (40 mg, 20%). MS (ISP) 419.1 [(M+H)+].
Reaction SMILES: [C:1]1([C:7](=[O:19])[CH2:8][CH2:9][CH2:10][C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3].O1CCCC1.O>C(OCC)(=O)C>[C:13]1([CH:11]([OH:12])[CH2:10][CH2:9][CH2:8][CH:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[OH:19])[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: O=C(CCCC(=O)c1ccccc1)c1ccccc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: OC(CCCC(O)c1ccccc1)c1ccccc1
Yield: 85 %

Procedure:
While cooled by an ice-bath and stirred intensely, 0.0 mol 1,5-diphenyl-1,5-pentandione was added dropwise slowly to a mixture of 3 g LiAlH4 and 100 ml anhydrous tetrahydrofuran. The mixture was heated refluxing for 5 hours, then cooled. Excess LiAlH4 was decomposed with water. After mixing completely the reaction mixture with ethyl acetate, the mixture was filtered, and the filtrate was dried over anhydrous sodium sulfate. The solvent was removed. Column chromatography gave 1,5-diphenyl-1,5-pentanediol as a white solid, and the yield was 85%. mp: 64-67° C. IR spectrum had a strong —OH absorption peak at 3400 cm−1, and had no —CO— absorption peak at about 1700 cm−1. This demonstrated that the reduction reaction was carried out completely.