Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([N+:14]([O-:16])=[O:15])[C:9]=2[CH3:17])[CH:5]=[CH:4][C:3]1=[O:18].[Br:19]Br>C(O)(=O)C>[Br:19][C:4]1[C:3](=[O:18])[N:2]([CH3:1])[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([N+:14]([O-:16])=[O:15])[C:9]=2[CH3:17])[CH:5]=1
Reactant: BrBr
Reactant: Cc1c(-c2ccc(=O)n(C)c2)cccc1[N+](=O)[O-]
Solvent: CC(=O)O
Product: Cc1c(-c2cc(Br)c(=O)n(C)c2)cccc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 18 h
Yield: 9.4 %

Procedure:
A 10-mL single-neck round-bottomed flask equipped with a magnetic stirrer and nitrogen inlet was purged with nitrogen and charged with 1-methyl-5-(2-methyl-3-nitrophenyl)pyridin-2-one (10) (0.60 mg, 2.46 mmol) and glacial acetic acid (5 mL). To the resulting solution bromine (0.59 g, 3.70 mmol) was added. The reaction was stirred for 18 h at room temperature. After this time the reaction was partitioned between water (25 mL) and ethyl acetate (75 mL). The organic layer was separated and washed with saturated aqueous sodium bicarbonate (2×25 mL), brine (50 mL) and dried over magnesium sulfate. The drying agent was removed by filtration and the filtrate concentrated to a constant weight under reduced pressure to afford 0.075 g (93%) of 3-bromo-1-methyl-5-(2-methyl-3-nitrophenyl)pyridin-2-one (11) as a yellow oil: 1H NMR (300 MHz, CDCl3) 7.83 (dd, 1H, J=7.2, 2.1 Hz), 7.75 (d, 1H, J=2.4 Hz), 7.42 (dd, 1H, J=7.8, 2.4 Hz), 7.38 (t, 1H, J=7.5 Hz), 7.29 (d, 1H, J=2.4 Hz), 3.70 (s, 3H), 2.40 (s, 3H); MS (ESI+) m/z 323 (M+H).
Reaction SMILES: [CH:1]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:2]=1[CH2:3][C:4]1[C:12]3[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=3[NH:6][C:5]=12.C([BH3-])#N.[Na+].[C:21](O)(=O)[CH3:22]>>[CH2:21]([N:6]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:12]=2[C@H:4]2[CH2:3][C:2]3[C:13]([C@@H:5]12)=[CH:14][CH:15]=[CH:16][CH:1]=3)[CH3:22]
Reactant: CC(=O)O
Reactant: c1ccc2c(c1)Cc1c-2[nH]c2ccccc12
Agent: [BH3-]C#N
Agent: [Na+]
Product: CCN1c2ccccc2[C@H]2Cc3ccccc3[C@H]21
Reaction time: 3 h

Procedure:
5,10-Dihydroindeno[1,2-b]indole (60.0 g, 0.29M) was vigorously stirred in glacial acetic acid (1000 cm3) and to it was added sodium cyanoborohydride (79 g, 1.25M) portion-wise over 40 minutes. After 3 hours stirring the reaction mixture was poured onto ice-water (2000 cm3) and the gelatinous solid which formed was separated and stirred with a mixture of ethyl acetate (75 cm3) and water (100 cm3). A colourless solid remained this was found to be unreacted starting material (19.0 g). The original filtrate was extracted with ethyl acetate (2×75 cm3) and the combined organic phases dried and evaporated. The residue was then partly dissolved in a mixture of 60°-80° C. petroleum ether (20 cm3) and ethyl acetate (40 cm3). The residual solid was removed and shown to be impure starting material (2.5 g). The filtrate was extracted with 2M hydrochloric acid (8×25 cm3) and the combined acid extracts were washed with ethyl acetate (2×15 cm3), prior to basification with 0.89 ammonia. The oil which separated was extracted into ethyl acetate (6×25 cm3) and the combined organic layers were then dried and evaporated to give the title compound as a colourless oil. Yield: 34 g, 75%. 1H NMR (CDCl3) δ: 1.20 (3H, t, J=7.0 Hz), 3.05 (1H, dd, J=16.5 and 5.0 Hz), 3.38 (2H, q, J=7.0 Hz), 3.40 (1, dd, J=16.5 and 9.0 Hz), 4.12 (1H, ddd, J=9.0, 5.0 and 5.0 Hz), 5.11 (1H, d, J=9.0 Hz), 6.33 (1H, d, J=7.0 Hz), 6.57 (1H, dt, J=7.5 and 1.0 Hz), 7.02 (1H, t, J=8.0 Hz ), 7.08 (1H, d, J=8.0 Hz), 7.14-7.20 (3H, m), 7.34-7.40 (1H, m).
Reaction SMILES: [NH2:1][C:2]1[C:10]([CH3:11])=[CH:9][C:8]([C:12]2[CH:13]=[C:14]3[C:20]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[O:27][CH3:28])=[N:19][NH:18][C:15]3=[N:16][CH:17]=2)=[CH:7][C:3]=1[C:4]([OH:6])=O.O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1.[CH3:44][N:45]([CH3:54])[CH2:46][CH2:47][N:48]1[CH2:53][CH2:52][NH:51][CH2:50][CH2:49]1>CC(N(C)C)=O>[NH2:1][C:2]1[C:10]([CH3:11])=[CH:9][C:8]([C:12]2[CH:13]=[C:14]3[C:20]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[O:27][CH3:28])=[N:19][NH:18][C:15]3=[N:16][CH:17]=2)=[CH:7][C:3]=1[C:4]([N:51]1[CH2:52][CH2:53][N:48]([CH2:47][CH2:46][N:45]([CH3:54])[CH3:44])[CH2:49][CH2:50]1)=[O:6]
Reactant: CN(C)CCN1CCNCC1
Reactant: COc1ccccc1-c1n[nH]c2ncc(-c3cc(C)c(N)c(C(=O)O)c3)cc12
Agent: O=C1OCCN1P(=O)(Cl)N1CCOC1=O
Solvent: CC(=O)N(C)C
Product: COc1ccccc1-c1n[nH]c2ncc(-c3cc(C)c(N)c(C(=O)N4CCN(CCN(C)C)CC4)c3)cc12
Yield: 30.8 %

Procedure:
45 mg (0.12 mmol) of 2-amino-5-[3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-3-methyl-benzoic acid and 40 mg (0.16 mmol) of bis(2-oxo-3-oxazolidinyl)phosphinic chloride were dissolved in 2 mL of dimethyl acetamide. 45 μL (approx. 0.2 mmol; density unknown) of 1-(2-dimethylaminoethyl)-piperazine was added and the mixture irradiated in a Personal Chemistry® Optimizer to 120° C. for 30 min. The resulting crude was directly purified by mass-triggered reverse-phase HPLC to afford 19 mg (37 μmol, 31%) of {2-amino-5-[3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-3-methyl-phenyl}-[4-(2-dimethylamino-ethyl)-piperazin-1-yl]-methanone as an ivory solid. 1H NMR (500 MHz, DMSO-d6) δ 13.71 (s, br., 1H), 8.75 (d, 1H), 8.16 (d, 1H), 7.63 (dd, 1H), 7.46 (dd(d), 1H), 7.44 (m, 1H), 7.22 (m, 1H), 7.21 (m, 1H), 7.09 (dd(d, 1H), 5.01 (s, 2H), 3.84 (s, 3H), 3.48 (m, br., 4H), 2.45-2.30 (m, 6H), 2.19 (s, 3H), 2.13 (s, 6H), MS: m/z 514.2 (M+H+).
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([N:20]3[C@H:24]([CH3:25])[CH2:23][CH2:22][C@H:21]3[CH3:26])=[O:19])=[CH:14][CH:13]=2)=[CH:8][CH:7]=1.[CH:27]([NH2:30])([CH3:29])[CH3:28]>>[CH3:26][C@@H:21]1[CH2:22][CH2:23][C@@H:24]([CH3:25])[N:20]1[C:18]([C:15]1[CH:16]=[CH:17][C:12]([C:9]2[CH:10]=[CH:11][C:6]([O:5][CH2:4][CH2:3][CH2:2][NH:30][CH:27]([CH3:29])[CH3:28])=[CH:7][CH:8]=2)=[CH:13][CH:14]=1)=[O:19]
Reactant: CC(C)N
Reactant: C[C@@H]1CC[C@@H](C)N1C(=O)c1ccc(-c2ccc(OCCCCl)cc2)cc1
Product: CC(C)NCCCOc1ccc(-c2ccc(C(=O)N3[C@H](C)CC[C@H]3C)cc2)cc1

Procedure:
The product from Example 4A and isopropylamine were processed as described in Example 10F to provide the title compound.
Reaction SMILES: Br[C:2]1[C:10]2[CH2:9][CH2:8][N:7]([C:11]3[CH:16]=[CH:15][C:14]([N:17]4[CH:22]=[CH:21][CH:20]=[CH:19][C:18]4=[O:23])=[CH:13][CH:12]=3)[C:6](=[O:24])[C:5]=2[N:4]([C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)[N:3]=1.[Li+].[Cl-].Cl.C1C[O:39][CH2:38][CH2:37]1>>[C:38]([C:2]1[C:10]2[CH2:9][CH2:8][N:7]([C:11]3[CH:16]=[CH:15][C:14]([N:17]4[CH:22]=[CH:21][CH:20]=[CH:19][C:18]4=[O:23])=[CH:13][CH:12]=3)[C:6](=[O:24])[C:5]=2[N:4]([C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)[N:3]=1)(=[O:39])[CH3:37]
Reactant: C1CCOC1
Reactant: COc1ccc(-n2nc(Br)c3c2C(=O)N(c2ccc(-n4ccccc4=O)cc2)CC3)cc1
Agent: Cl
Agent: [Cl-]
Agent: [Li+]
Product: COc1ccc(-n2nc(C(C)=O)c3c2C(=O)N(c2ccc(-n4ccccc4=O)cc2)CC3)cc1
Temperature: 25 °C

Procedure:
To 3-bromo-1-(4-methoxy-phenyl)-6-[4-(2-oxo-2H-pyridin-1-yl)-phenyl]-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-one (0.11 g, 0.22 mmol) was added THF (25 mL), 1-(ethoxyvinyl)tributyltin (0.078 mL, 0.23 mmol), and LiCl (27 mg, 0.65 mmol) and the mixture was degassed with N2 for 15 min. Tetrakistriphenylphosphine Palladium(0) (12 mg, 0.01 mmol) was added and the reaction was heated to reflux 24 h. The reaction was cooled to rt and treated with 1N HCl for 24 h. After extraction with EtOAc and drying (MgSO4), the product was purified by silica gel (mixed with KF) chromatography using 0-3% MeOH in CH2Cl2 and by HPLC to afford 6 mg (6%); High Resolution Mass Spec (M+H)+ for C26H23N4O4 455.1713.
Reaction SMILES: [Na].[NH2:2][C:3]1[C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[C:11]2[C:5](=[CH:6][CH:7]=[C:8]([CH2:18][C:19](=[O:22])[NH:20][OH:21])[CH:9]=[CH:10]2)[C:4]=1[C:23]([O:25][CH2:26][CH3:27])=[O:24].[CH2:28]([N:30]([CH2:35][CH3:36])[CH2:31][CH2:32][CH2:33]Cl)[CH3:29]>>[NH2:2][C:3]1[C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[C:11]2[C:5](=[CH:6][CH:7]=[C:8]([CH2:18][C:19](=[O:22])[NH:20][O:21][CH2:33][CH2:32][CH2:31][N:30]([CH2:35][CH3:36])[CH2:28][CH3:29])[CH:9]=[CH:10]2)[C:4]=1[C:23]([O:25][CH2:26][CH3:27])=[O:24]
Reactant: CCOC(=O)c1c2ccc(CC(=O)NO)ccc-2c(C(=O)OCC)c1N
Reactant: CCN(CC)CCCCl
Agent: [Na]
Product: CCOC(=O)c1c2ccc(CC(=O)NOCCCN(CC)CC)ccc-2c(C(=O)OCC)c1N
Yield: 42 %

Procedure:
In an analogous manner to that described in Example 1, from diethyl 2-amino-6-[(hydroxycarbamoyl)-methyl]-azulene-1,3-dicarboxylate sodium and 3-diethylamino-propyl chloride the title compound of m.p. 125-127° C. is obtained in 42% yield.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][N:11]=[CH:10][C:9]=1[NH:14][CH2:15][C:16]([F:19])([F:18])[F:17].[CH3:20][S:21]([C:24]1[CH:25]=[C:26]([CH:30]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:32]=1)[C:27](O)=[O:28])(=[O:23])=[O:22]>>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][N:11]=[CH:10][C:9]=1[N:14]([CH2:15][C:16]([F:19])([F:17])[F:18])[C:27](=[O:28])[C:26]1[CH:30]=[C:31]([C:33]([F:36])([F:34])[F:35])[CH:32]=[C:24]([S:21]([CH3:20])(=[O:23])=[O:22])[CH:25]=1
Reactant: FC(F)(F)CNc1cnccc1-c1ccccc1Cl
Reactant: CS(=O)(=O)c1cc(C(=O)O)cc(C(F)(F)F)c1
Product: CS(=O)(=O)c1cc(C(=O)N(CC(F)(F)F)c2cnccc2-c2ccccc2Cl)cc(C(F)(F)F)c1

Procedure:
The title compound was prepared in analogy to example 90, from 4-(2-chlorophenyl)-N-(2,2,2-trifluoroethyl)pyridin-3-amine and 3-(methylsulfonyl)-5-(trifluoromethyl)benzoic acid (example 114, intermediate a) after a reaction time of 18 hours at room temperature. The compound was purified by silica gel chromatography on a 20 g column using an MPLC (Flashmaster) system eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100). Further purification by preparative HPLC (Gemini NX) with a gradient of MeOH:water (containing 0.05% formic acid) (80:20 to 98:2). Colorless solid (31%). MS (ESI): m/z=537.045 [M+H]+.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][C:8](=[O:11])[NH:7][C:6]=2[C:12]=1[O:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[CH3:20][N:21]1[CH:26]=[C:25](B2OC(C)(C)C(C)(C)O2)[C:24]2[CH:36]=[CH:37][N:38]([S:39]([C:42]3[CH:47]=[CH:46][C:45]([CH3:48])=[CH:44][CH:43]=3)(=[O:41])=[O:40])[C:23]=2[C:22]1=[O:49]>>[CH3:20][N:21]1[CH:26]=[C:25]([C:2]2[CH:3]=[CH:4][C:5]3[O:10][CH2:9][C:8](=[O:11])[NH:7][C:6]=3[C:12]=2[O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:24]2[CH:36]=[CH:37][N:38]([S:39]([C:42]3[CH:47]=[CH:46][C:45]([CH3:48])=[CH:44][CH:43]=3)(=[O:41])=[O:40])[C:23]=2[C:22]1=[O:49]
Reactant: O=C1COc2ccc(Br)c(Oc3ccccc3)c2N1
Reactant: Cc1ccc(S(=O)(=O)n2ccc3c(B4OC(C)(C)C(C)(C)O4)cn(C)c(=O)c32)cc1
Product: Cc1ccc(S(=O)(=O)n2ccc3c(-c4ccc5c(c4Oc4ccccc4)NC(=O)CO5)cn(C)c(=O)c32)cc1

Procedure:
This compound was synthesized according to the procedure of Example 10, Step 5, using 6-bromo-5-phenoxy-2H-1,4-benzoxazin-3(4H)-one and 6-methyl-1-[(4-methylphenyl)sulfonyl]-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one as the starting materials. LCMS calculated for C29H24N3O6S (M+H)+: m/z=542.1. found: 542.0.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:21]([O:23][C:24]([C:26]1[C:36]([NH2:37])=[N:35][C:29]2[N:30]=[C:31](Cl)[N:32]=[CH:33][C:28]=2[CH:27]=1)=[O:25])[CH3:22].CCCCCC.C(OCC)(=O)C>O1CCOCC1>[CH2:21]([O:23][C:24]([C:26]1[C:36]([NH2:37])=[N:35][C:29]2[N:30]=[C:31]([NH:20][C:17]3[CH:16]=[CH:15][C:14]([N:11]4[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH2:10]4)=[CH:19][CH:18]=3)[N:32]=[CH:33][C:28]=2[CH:27]=1)=[O:25])[CH3:22]
Reactant: CCOC(=O)c1cc2cnc(Cl)nc2nc1N
Reactant: CC(C)(C)OC(=O)N1CCN(c2ccc(N)cc2)CC1
Solvent: C1COCCO1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: CCOC(=O)c1cc2cnc(Nc3ccc(N4CCN(C(=O)OC(C)(C)C)CC4)cc3)nc2nc1N
Yield: 16 %

Procedure:
A solution of the product of Example 12 and the product of Example 129 in dioxane is heated under reflux for 1.5 hours. The reaction is poured into hexane/ethyl acetate (1:1), and the solid is collected. Flash chromatography using dichloromethane as eluant gave 0.08 g (16%) of the product as a solid.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]([N:11]2[C:15]([C:16]3[CH:21]=[CH:20][C:19](Br)=[CH:18][CH:17]=3)=[CH:14][C:13]([C:23]([F:26])([F:25])[F:24])=[N:12]2)=[N:9][CH:10]=1)(=[O:4])=[O:3].C[Si]([C:31]#[CH:32])(C)C.C(OCC)(=O)C.CCCCCC.C(=O)([O-])[O-].[K+].[K+]>C(N(CC)CC)C.CO.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>[CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]([N:11]2[C:15]([C:16]3[CH:21]=[CH:20][C:19]([C:31]#[CH:32])=[CH:18][CH:17]=3)=[CH:14][C:13]([C:23]([F:26])([F:25])[F:24])=[N:12]2)=[N:9][CH:10]=1)(=[O:4])=[O:3]
Reactant: CS(=O)(=O)c1ccc(-n2nc(C(F)(F)F)cc2-c2ccc(Br)cc2)nc1
Reactant: C#C[Si](C)(C)C
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: [K+]
Solvent: CO
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: C#Cc1ccc(-c2cc(C(F)(F)F)nn2-c2ccc(S(C)(=O)=O)cn2)cc1
Temperature: 80 °C
Reaction time: 0.5 h

Procedure:
5-Methylsulfonyl-2-[5-(4-bromophenyl)-3-trifluoromethyl-1H-pyrazol-1-yl]pyridine (230 mg), Cul (5 mg), Pd(PPh3)4 (30 mg) were mixed in triethylamine (2.5 mL), followed by the addition of trimethylsilyl acetylene (0.182 mL), and the reaction mixture was heated at 80° C. for 2 hours. TLC in 1:1 of ethyl acetate/hexane showed complete conversion of the starting material to the product. The solvent was removed in vacuo to give the crude product. This crude material was then dissolved in methanol (2.5 mL), followed by the addition of potassium carbonate (20 mg). The reaction mixture was stirred at room temperature for 30 minutes. After filtration, the solvent was removed in vacuo to give the crude product which was purified by flash chromatography using 70:30 of methylene chloride/hexane to give the title compound (41 mg).
Reaction SMILES: Cl[C:2]([O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:3].[F:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[C:19]1[N:20]=[C:21]2[C:26]3[CH2:27][NH:28][CH2:29][CH2:30][C:25]=3[NH:24][C:23](=[O:31])[N:22]2[CH:32]=1.C(N(CC)CC)C>CN(C=O)C>[C:2]([N:28]1[CH2:29][CH2:30][C:25]2[NH:24][C:23](=[O:31])[N:22]3[CH:32]=[C:19]([C:14]4[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=4[F:12])[N:20]=[C:21]3[C:26]=2[CH2:27]1)([O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:3]
Reactant: O=C(Cl)OCc1ccccc1
Reactant: O=c1[nH]c2c(c3nc(-c4ccccc4F)cn13)CNCC2
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: O=C(OCc1ccccc1)N1CCc2[nH]c(=O)n3cc(-c4ccccc4F)nc3c2C1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
Benzyl chloroformate (57 uL, 0.4 mmol) was added to a solution of 2-(2-fluorophenyl)-7,8,9,10-tetrahydro-imidazo[1,2-c]pyrido[3,4-e] pyrimidin-5(6H)-one (124 mg, 0.4 mmol) and triethylamine (74 uL, 0.5 mmol) in DMF (1 mL) at room temperature. The reaction mixture was stirred for 1 hour, then poured into ice water. The precipitate was collected, washed with 95% ethanol and ether, and subsequently dried to give 9-Carbobenzyloxy-2-(2-fluorophenyl)-7,8,9,10-tetrahydro-imidazo[1,2-c]pyrido[3,4-e] pyrimidin-5(6H)-one (Compound 44). Recrystallization from aqueous ethanol afforded Compound 41 as an off-white solid, m.p. 250° C. (d).
Reaction SMILES: [F:1][C:2]([F:35])([CH2:31][CH2:32][C:33]#[N:34])[C:3]([F:30])([F:29])[C:4]([F:28])([F:27])[C:5]([F:26])([F:25])[C:6]([F:24])([F:23])[C:7]([F:22])([F:21])[C:8]([F:20])([F:19])[C:9]([F:18])([F:17])[C:10]([F:16])([F:15])[C:11]([F:14])([F:13])[F:12].N.[H][H]>[Co].O1CCCC1>[F:1][C:2]([F:35])([CH2:31][CH2:32][CH2:33][NH2:34])[C:3]([F:29])([F:30])[C:4]([F:27])([F:28])[C:5]([F:25])([F:26])[C:6]([F:24])([F:23])[C:7]([F:21])([F:22])[C:8]([F:20])([F:19])[C:9]([F:18])([F:17])[C:10]([F:16])([F:15])[C:11]([F:14])([F:13])[F:12]
Reactant: [H][H]
Reactant: N#CCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Agent: [Co]
Agent: N
Solvent: C1CCOC1
Product: NCCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Temperature: 110 °C
Yield: 94.3 %

Procedure:
A one liter Hastelloy pressure vessel was charged with 126.1 g (0.22 mol) of 3-(perfluorodecyl)propionitrile (Du Pont), 20 g of Rainey cobalt, 50 g of anhydrous ammonia and 300 mL of tetrahydrofuran. The vessel was pressured to 800 psi with hydrogen and heated to 110° C. The hydrogen pressure was adjusted to 1500 psi and maintained for 20 hours. The vessel was cooled to room temperature and vented. The solution was decanted and the reaction vessel was rinsed with tetrahydrofuran. The combined solutions were filtered through Celite® and concentrated on a rotary evaporator at 50° C. The product was distilled through a Vigreux column to give 119.8 g of product, bp 78-80° C. at 1.2 mm as a waxy solid which melted at 53-55° C. The product was redistilled through an 8 in. Vigreux column to give 107.7 g of a center cut, bp 70° C. at 1.8 mm.
Reaction SMILES: O=[CH:2][C@@H:3]([C@H:5]([C@@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])[OH:4].[CH2:13]([NH2:31])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30]>>[CH:2]1([CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][NH2:31])[O:10][C@H:9]([CH2:11][OH:12])[C@@H:7]([OH:8])[C@H:5]([OH:6])[C@H:3]1[OH:4]
Reactant: CCCCCCCCCCCCCCCCCCN
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Product: NCCCCCCCCCCCCCCCCCCC1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O

Procedure:
The preparation is analogous to Example 1, starting from 11 g of glucose and 20 g of octadecylamine.
Reaction SMILES: C[O:2][C:3](=[O:14])[C:4]([CH3:13])([C@H:6]1[CH2:11][CH2:10][CH2:9][N:8]([CH3:12])[CH2:7]1)[CH3:5].[OH-].[Na+]>CO>[CH3:13][C:4]([C@H:6]1[CH2:11][CH2:10][CH2:9][N:8]([CH3:12])[CH2:7]1)([CH3:5])[C:3]([OH:14])=[O:2]
Reactant: COC(=O)C(C)(C)[C@H]1CCCN(C)C1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CN1CCC[C@H](C(C)(C)C(=O)O)C1
Temperature: 60 °C
Reaction time: 6 h

Procedure:
0.489 g of (R)-2-methyl-2-(1-methyl-piperidin-3-yl)-propionic acid methyl ester are taken up in 4 ml of methanol and the mixture is admixed with 4 ml of 3M NaOH. The mixture is then stirred at 60° C. for 6 hours. The methanol is removed in vacuo and the aqueous residue acidified with 2M HCl to pH 7. The mixture is concentrated under reduced pressure. The residue is taken up in 10 ml of ethanol and the insoluble salts removed by filtration. Concentration of the filtrate under reduced pressure provides the title compound as a colourless solid which can be used without further purification.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:7]([CH3:19])=[N:8][C:9]([O:16][CH2:17][CH3:18])=[C:10]([NH2:15])[C:11]=1[NH:12][CH2:13][CH3:14])=[O:5])[CH3:2].C(O)(=O)C.[N:24]([O-])=O.[Na+]>O>[CH2:1]([O:3][C:4]([C:6]1[C:11]2[N:12]([CH2:13][CH3:14])[N:24]=[N:15][C:10]=2[C:9]([O:16][CH2:17][CH3:18])=[N:8][C:7]=1[CH3:19])=[O:5])[CH3:2]
Reactant: CCNc1c(N)c(OCC)nc(C)c1C(=O)OCC
Reactant: O=N[O-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: CCOC(=O)c1c(C)nc(OCC)c2nnn(CC)c12
Reaction time: 8 h
Yield: 75 %

Procedure:
26.7 g. of 5-amino-4-ethylamino-6-ethoxy-2-methylpyridine-3-carboxylic acid ethyl ester (0.1 mol.) are dissolved in 100 ml. of acetic acid. At room temperature 7.5 g. of sodium nitrite in 20 ml. of water are added dropwise with continual stirring. The temperature is kept below 20°. The mixture is stirred overnight and then evaporated to dryness. 100 ml. of water are added to the residue which is then extracted three times with 50 ml. portions of ether. The organic layer is collected, dried over sodium sulfate, filtered and the solvent distilled off. The residue of 4-ethoxy-1-ethyl-6-methyl-1H-1,2,3-triazolo[4,5-c]pyridine-7-carboxylic acid ethyl ester is recrystallized from ligroin, yield 75%, m.p. 56°-58°.
Reaction SMILES: [C:1]1([C:7]2[C:11]([OH:12])=[C:10]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[NH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[O-].[Na+].CO.[CH2:24](Cl)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>O>[CH2:24]([O:12][C:11]1[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[N:8][NH:9][C:10]=1[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: ClCc1ccccc1
Reactant: Oc1c(-c2ccccc2)n[nH]c1-c1ccccc1
Agent: C[O-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: c1ccc(COc2c(-c3ccccc3)n[nH]c2-c2ccccc2)cc1
Temperature: 60 °C
Reaction time: 8 h

Procedure:
A mixture of 3,5-diphenyl-4-pyrazolol (10 g, 0.042 mole), sodium methoxide (2.27 g, 0.042 mole) and methanol (60 ml) is heated at 60° C. for 2 hours. Then benzyl chloride is added slowly at 60° C. A white solid forms. Heating is continued overnight at 60° C. The reaction mixture is examined by glc and the reaction is found to be complete. The mixture is poured into water and the solid isolated by filtration. The solid is washed well with water, dried and recrystallized from acetonitrile to give pale yellow crystals, melting point 152°-152.5° C.
Reaction SMILES: [CH3:1][C:2]([CH3:15])([CH3:14])[CH2:3][NH:4][CH2:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)=[O:7].[Br:16][CH2:17][C:18](Br)=[O:19]>C1COCC1>[Br:16][CH2:17][C:18]([N:4]([CH2:3][C:2]([CH3:15])([CH3:14])[CH3:1])[CH2:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)=[O:7])=[O:19]
Reactant: O=C(Br)CBr
Reactant: CC(C)(C)CNCC(=O)N1CCOCC1
Solvent: C1CCOC1
Product: CC(C)(C)CN(CC(=O)N1CCOCC1)C(=O)CBr
Yield: 37.3 %

Procedure:
To a stirred solution of the above 2-(2,2-dimethyl-propylamino)-1-morpholin-4-yl-ethanone (0.18 g, 0.8 mmol) in THF (2.0 mL), a solution of bromoacetyl bromide (0.15 mL, 1.6mmol) in THF (2.0 mL) was added, dropwise at −78° C., under nitrogen. After 3 h the reaction was concentrated and the resulting residue was diluted with methylene chloride and saturated NaHCO3. The layers were separated and the aqueous phase was extracted with methylene chloride. The combined organic layers were dried (MgSO4), filtered and concentrated to give the crude product. Purification via silica gel flash chromatography, eluting with EtOAc, flow rate 30 mL/min, gave 0.10 g (36%) of 2-bromo-N-(2,2-dimethyl-propyl)-N-(2-morpholin-4-yl-2-oxo-ethyl)-acetamide.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[O:11][CH3:12])[C:7](=[O:13])[CH2:6][C:5]2([CH3:15])[CH3:14].[CH3:16][CH:17](O)[CH:18]=[CH2:19].C1(C)C=CC(S(O)(=O)=O)=CC=1.O>COC(OC)(C)C>[CH2:16]([CH:6]1[C:5]([CH3:15])([CH3:14])[C:4]2[C:8](=[CH:9][C:10]([O:11][CH3:12])=[C:2]([Cl:1])[CH:3]=2)[C:7]1=[O:13])[CH:17]=[CH:18][CH3:19]
Reactant: COc1cc2c(cc1Cl)C(C)(C)CC2=O
Reactant: C=CC(C)O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: COC(C)(C)OC
Solvent: O
Product: CC=CCC1C(=O)c2cc(OC)c(Cl)cc2C1(C)C
Yield: 66 %

Procedure:
A solution of 14.5 g of 5-chloro-6-methoxy-3,3-dimethyl-1-indanone, 13.3 ml of 3-buten-2-ol and 300 mg of p-toluenesulfonic acid in 150 ml of 2,2-dimethoxy-propane was boiled under reflux for 71 hours on a water separator filled with molecular sieve (0.4 nm 2 mm, pearl shaped). The reaction mixture was subsequently concentrated in a vacuum and purified by column chromatography on silica gel (hexane/diethyl ether 6:1). In addition to 2.25 g of educt, there were obtained 11.9 g (66%) of (RS)-2-(2-buten-1-yl)-5-chloro-6-methoxy-3,3-dimethyl-1-indanone as a pale yellow solid with m.p. 86°.
Reaction SMILES: [CH3:1][C:2]1[O:3][C:4]([C:7]2[CH:12]=[CH:11][C:10]([N+:13]([O-])=O)=[CH:9][CH:8]=2)=[N:5][N:6]=1>CO.[Pd]>[CH3:1][C:2]1[O:3][C:4]([C:7]2[CH:12]=[CH:11][C:10]([NH2:13])=[CH:9][CH:8]=2)=[N:5][N:6]=1
Reactant: Cc1nnc(-c2ccc([N+](=O)[O-])cc2)o1
Agent: [Pd]
Solvent: CO
Product: Cc1nnc(-c2ccc(N)cc2)o1
Yield: 95.6 %

Procedure:
2-Methyl-5-(4-nitro-phenyl)-[1,3,4]oxadiazole (0.930 g, 4.54 mmol) was dissolved in MeOH. To this was added 10% palladium on carbon (0.06 g) and the mixture shaken under hydrogen pressure (35 psi, Parr apparatus) until the reaction was complete (LCMS monitored). The solids were filtered off and rinsed with MeOH. The filtrate was concentrated to give the title compound (0.76 g). MS (ESI+) for m/z 176 (M+H)+.