Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]([C@H:4]1[C@H:16]([O:17]C(=O)C)[C@H:15]([O:21]C(=O)C)[C@H:14]([CH3:25])[O:13][CH:5]1[S:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[N+:2]=[N-:3].C([O-])([O-])=O.[K+].[K+]>CO>[N:1]([C@H:4]1[C@H:16]([OH:17])[C@H:15]([OH:21])[C@H:14]([CH3:25])[O:13][CH:5]1[S:6][C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1)=[N+:2]=[N-:3]
Reactant: CC(=O)O[C@@H]1[C@H](OC(C)=O)[C@H](C)OC(Sc2ccccc2)[C@H]1N=[N+]=[N-]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: C[C@@H]1OC(Sc2ccccc2)[C@@H](N=[N+]=[N-])[C@H](O)[C@@H]1O
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 91.1 %

Procedure:
To a solution of 22 (4.40 g, 12.1 mmol) in 120 mL of methanol is added K2CO3 (5.97 g, 36.2 mmol). The reaction mixture is stirred at room temperature for 1.5 h and then neutralized with amberlite resin, filtered, concentrated and purified by flash chromatography (5% methanol/CH2Cl2) to yield 3.10 g (91%, 2 steps) of phenyl 2-azido-2,6-dideoxy-1-thio-L-galactopyranoside (23) as a 2.5:1 (α:β) mixture of anomers: Rf 0.10 (25% EtOAc/petroleum ether); 1H NMR (CDCl3, 270 MHz) mixture of anomers, δ 7.61-7.27 (m, 10H), 5.61 (d, J=5.3 Hz, 1H, H-1α), 4.50 (q, J=6.6 Hz, 1H, H-5α), 4.42 (d, J=9.9 Hz, 1H, H-1β), 4.11 (dd, J=10.1, 5.4 Hz, 2H, H-3α,β), 3.88-3.85 (m, 3H), 3.73 (br s, 1H), 3.63 (q, J=6.3 Hz, 1H, H-5β), 3.59-3.40 (m, 1H), 2.81 (br s, 1H, OH), 2.47 (br s, 1H, OH), 2.23 (br s, 1H, OH), 1.72 (br s, 1H, OH), 1.37 (d, J=6.3 Hz, 3H, H-6β), 1.30 (d, J=6.6 Hz, 3H, H-6α).
Reaction SMILES: [CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH:2]1[N:10]1[C:18]([S:19][CH2:20][CH2:21][CH2:22][OH:23])=[C:17]2[C:12]([N:13]([CH:27]([CH3:29])[CH3:28])[C:14](=[O:26])[N:15]([CH3:25])[C:16]2=[O:24])=[CH:11]1.S([O-])(O[O-])(=O)=[O:31].[K+].[K+].OOS([O-])=O.[K+]>CO.O>[CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH:2]1[N:10]1[C:18]([S:19]([CH2:20][CH2:21][CH2:22][OH:23])=[O:31])=[C:17]2[C:12]([N:13]([CH:27]([CH3:29])[CH3:28])[C:14](=[O:26])[N:15]([CH3:25])[C:16]2=[O:24])=[CH:11]1
Reactant: CC(C)n1c(=O)n(C)c(=O)c2c(SCCCO)n(C3Cc4ccccc4C3)cc21
Reactant: O=S(=O)([O-])O[O-]
Agent: O=S([O-])OO
Agent: [K+]
Solvent: O
Solvent: CO
Product: CC(C)n1c(=O)n(C)c(=O)c2c(S(=O)CCCO)n(C3Cc4ccccc4C3)cc21
Reaction time: 0.25 h

Procedure:
6-(2,3-Dihydro-1H-inden-2-yl)-5-[(3-hydroxypropyl)thio]-3-methyl-1-(1-methylethyl)-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione (100 mg) was dissolved in methanol (40 ml). Water (10 ml) and potassium peroxymonosulphate (commercially sold under the trade mark "OXONE") (185 mg) were added and the solution was stirred for 15 minutes. The reaction mixture was diluted with water and then extracted with ethyl acetate thrice. The extracts were combined, washed with brine, then dried, filtered and the solvent was evaporated. The resultant oil was triturated with isohexane, then recrystallised from ethyl acetate-isohexane mixtures to give the title compound (15 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[N:6][CH:5]=[C:4]2[S:8][C:9]([C:11]3[S:15][C:14]([NH:16][CH2:17][C@@H:18]([NH:30]C(=O)OC(C)(C)C)[CH2:19][C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:29])([F:28])[F:27])[CH:21]=4)=[N:13][N:12]=3)=[CH:10][C:3]=12.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:30][C@@H:18]([CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:27])([F:29])[F:28])[CH:21]=1)[CH2:17][NH:16][C:14]1[S:15][C:11]([C:9]2[S:8][C:4]3=[CH:5][N:6]=[CH:7][C:2]([Cl:1])=[C:3]3[CH:10]=2)=[N:12][N:13]=1
Reactant: CC(C)(C)OC(=O)N[C@H](CNc1nnc(-c2cc3c(Cl)cncc3s2)s1)Cc1cccc(C(F)(F)F)c1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: N[C@H](CNc1nnc(-c2cc3c(Cl)cncc3s2)s1)Cc1cccc(C(F)(F)F)c1

Procedure:
tert-Butyl (S)-1-(5-(4-chlorothieno[2,3-c]pyridin-2-yl)-1,3,4-thiadiazol-2-ylamino)-3-(3-(trifluoromethyl)phenyl)propan-2-ylcarbamate (0.070 g, 0.12 mmol) was treated with 1 mL TFA in 1 mL DCM for 30 minutes. After removing the solvent, the residue was mixed with 10 mL 2M ammonia in MeOH. The solvent was removed again and the remaining residue was subjected to a silica gel flash chromatography separation using 3.5% 2M ammonia MeOH solution in DCM as the eluant. An-off white solid was obtained as the pure product (0.03 g, y=52%). LCMS (API-ES) m/z (%): 470.1 (100%, M++H); 1H NMR (300 MHz, CDCL3) δ ppm 1.48-1.82 (b, 3H) 2.72 (dd, J=13.56, 8.48 Hz, 1H) 3.00 (dd, J=13.66, 4.99 Hz, 1H) 3.26-3.35 (m, 1H) 3.40-3.50 (m, 1H) 3.61 (dd, J=12.72, 3.67 Hz, 1H) 7.41-7.56 (m, 6H) 8.46 (s, 1H) 8.95 (s, 1H).
Reaction SMILES: Cl[C:2]1[N:7]=[N:6][C:5]([N:8]([CH3:19])[CH:9]2[CH2:14][C:13]([CH3:16])([CH3:15])[NH:12][C:11]([CH3:18])([CH3:17])[CH2:10]2)=[CH:4][CH:3]=1.[CH2:20]([O:27][C:28]1[CH:37]=[C:36]2[C:31]([CH:32]=[CH:33][C:34]([O:38][CH2:39][CH2:40][CH2:41][NH:42][C:43](=[O:49])[O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[CH:35]2)=[CH:30][C:29]=1B1OC(C)(C)C(C)(C)O1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>>[CH2:20]([O:27][C:28]1[CH:37]=[C:36]2[C:31]([CH:32]=[CH:33][C:34]([O:38][CH2:39][CH2:40][CH2:41][NH:42][C:43](=[O:49])[O:44][C:45]([CH3:47])([CH3:46])[CH3:48])=[CH:35]2)=[CH:30][C:29]=1[C:2]1[N:7]=[N:6][C:5]([N:8]([CH3:19])[CH:9]2[CH2:14][C:13]([CH3:16])([CH3:15])[NH:12][C:11]([CH3:18])([CH3:17])[CH2:10]2)=[CH:4][CH:3]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: CC(C)(C)OC(=O)NCCCOc1ccc2cc(B3OC(C)(C)C(C)(C)O3)c(OCc3ccccc3)cc2c1
Reactant: CN(c1ccc(Cl)nn1)C1CC(C)(C)NC(C)(C)C1
Product: CN(c1ccc(-c2cc3ccc(OCCCNC(=O)OC(C)(C)C)cc3cc2OCc2ccccc2)nn1)C1CC(C)(C)NC(C)(C)C1

Procedure:
Intermediate 1-1 (242.5 mg, 0.86 mmol) and tert-butyl (3-((7-(benzyloxy)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-2-yl)oxy)propyl)carbamate (662 mg, 1.18 mmol) were reacted following GENERAL METHOD 1-1 for Suzuki coupling with the following modifications: Instead of SCX purification, the crude material was purified by flash chromatography (eluting with 1-15% 7N NH3 in MeOH/DCM) to afford a yellow oil. The oil was triturated with Et2O then concentrated in vacuo to dryness affording tert-butyl (3-((7-(benzyloxy)-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-yl)oxy)propyl)carbamate a pale-yellow solid (492 mg, 83% yield). MS (M+1)=654.8.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]([OH:6])=[O:5].[C:7]1(=O)[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[C:9](=[O:16])[O:8]1.C([O-])(=O)C.[K+]>C(O)(=O)C.C(OCC)(=O)C>[O:8]=[C:7]1[C:11]2[C:10](=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:9](=[O:16])[N:1]1[CH2:2][CH2:3][C:4]([OH:6])=[O:5]
Reactant: NCCC(=O)O
Reactant: O=C1OC(=O)c2ccccc21
Agent: CC(=O)[O-]
Agent: [K+]
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: O=C(O)CCN1C(=O)c2ccccc2C1=O
Temperature: 80 °C
Reaction time: 3 h

Procedure:
Into a 3-L 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 3-aminopropanoic acid (20 g, 224.48 mmol, 1.00 equiv) and 1,3-dihydro-2-benzofuran-1,3-dione (33.28 g, 224.69 mmol, 1.00 equiv) in acetic acid (1,200 mL). This was followed by the addition of potassium acetate (66.0 g, 672.49 mmol, 3.00 equiv) in several batches at 0° C. The resulting solution was stirred for 3 h at 80° C. in an oil bath. The resulting mixture was concentrated under vacuum. The reaction was then quenched by the addition of 150 mL of water. The solids were collected by filtration. This resulted in 40 g (81%) of 3-(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)propanoic acid as a white solid. Rf: 0.15 (in ethyl acetate:petroleum ether=1:1).
Reaction SMILES: F[C:2]1C=CC(N(C2C=CC(OC3C=CN=CC=3)=CC=2)C(=O)CC(N)=O)=CC=1.Cl[C:29]1[N:34]=[CH:33]N=[C:31]([O:35][C:36]2[CH:41]=[CH:40][C:39]([NH:42][C:43]([NH:45][C:46](=[O:55])[CH2:47][C:48]3[CH:53]=[CH:52][C:51]([F:54])=[CH:50][CH:49]=3)=[S:44])=[CH:38][C:37]=2F)[CH:30]=1>>[F:54][C:51]1[CH:52]=[CH:53][C:48]([CH2:47][C:46]([NH:45][C:43]([NH:42][C:39]2[CH:40]=[CH:41][C:36]([O:35][C:31]3[CH:2]=[CH:33][N:34]=[CH:29][CH:30]=3)=[CH:37][CH:38]=2)=[S:44])=[O:55])=[CH:49][CH:50]=1
Reactant: O=C(Cc1ccc(F)cc1)NC(=S)Nc1ccc(Oc2cc(Cl)ncn2)c(F)c1
Reactant: NC(=O)CC(=O)N(c1ccc(F)cc1)c1ccc(Oc2ccncc2)cc1
Product: O=C(Cc1ccc(F)cc1)NC(=S)Nc1ccc(Oc2ccncc2)cc1
Yield: 10 %

Procedure:
The title compound was prepared using 4-(4-aminophenoxy)pyridine (Compound A of Example 1) and a similar procedure outlined for the preparation of Compound C of Example 2. Yield: 10%. 1H NMR (CDCl3) δ 12.3 (s, 1H), 8.63 (s, 1H), 8.49, (d, 2H, J=6.2 Hz), 7.71 (d, 2H, J=8.9 Hz), 7.31-7.27 (m, 2H), 7.14-7.09 (m, 4H), 6.90 (dd, 2H, J=4.8, 1.4 Hz), 3.73 (s, 2H); MS (ESI+) m/z 382.2 (M+H)+.
Reaction SMILES: [C:1]1([S:7]([C:10]2[CH:18]=[C:17]([CH3:19])[C:16]3[N:15]([CH3:20])[C:14]4[CH2:21][CH:22]5[NH:26][CH:25]([C:13]=4[C:12]=3[C:11]=2C(OC(C)(C)C)=O)[CH2:24][CH2:23]5)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[ClH:34]>C(Cl)(Cl)Cl.C(OCC)C>[ClH:34].[C:1]1([S:7]([C:10]2[CH:11]=[C:12]3[C:16](=[C:17]([CH3:19])[CH:18]=2)[N:15]([CH3:20])[C:14]2[CH2:21][CH:22]4[NH:26][CH:25]([C:13]3=2)[CH2:24][CH2:23]4)(=[O:8])=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: Cc1cc(S(=O)(=O)c2ccccc2)c(C(=O)OC(C)(C)C)c2c3c(n(C)c12)CC1CCC3N1
Agent: Cl
Solvent: CCOCC
Solvent: ClC(Cl)Cl
Product: Cc1cc(S(=O)(=O)c2ccccc2)cc2c3c(n(C)c12)CC1CCC3N1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a solution of the product of step D (104 mg, 0.22 mmol) in chloroform (1 mL) was added 2 M HCl in diethyl ether solution (5 mL). The reaction was stirred at 0° C. for 1 h then allowed to warm to ambient temperature overnight. The mixture was concentrated in vacuo, made basic with sat. sodium bicarbonate solution and extracted with chloroform. The organic extract was dried over anhydrous sodium sulfate, concentrated in vacuo and the resulting residue purified by flash column chromatography (SiO2, 90:9.9:0.1 dichloromethane/methanol/ammonium hydroxide). The free-base was treated directly with 1.25 M HCl in methanol (2 mL) and the resulting solution concentrated in vacuo to give 2-phenylsulfonyl-4,5-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole hydrochloride (65 mg, 72%, AUC HPLC 98.7%) as a white solid: mp 244-248° C.; 1H NMR (CD3OD, 300 MHz): δ 8.08 (d, J=1.5 Hz, 1H), 7.90-7.98 (m, 2H), 7.49-7.63 (m, 3H), 7.38-7.43 (m, 1H), 5.26 (d, J=4.8 Hz, 1H), 4.49-4.58 (m, 1H), 3.94 (s, 3H), 3.44 (dd, J=17.1 Hz, J=4.5 Hz, 1H), 3.02 (d, J=17.4 Hz, 1H), 2.99 (s, 3H), 2.19-2.52 (m, 3H), 1.91-2.20 (m, 1H); APCI MS m/z 367 [M+H]+.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([OH:11])[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9].C(=O)([O-])[O-].[K+].[K+].[CH2:18](Br)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>C(#N)C>[CH2:18]([O:11][C:4]1[CH:5]=[CH:6][C:7]([N+:8]([O-:10])=[O:9])=[C:2]([F:1])[CH:3]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: O=[N+]([O-])c1ccc(O)cc1F
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: O=[N+]([O-])c1ccc(OCc2ccccc2)cc1F
Reaction time: 0.5 h
Yield: 96.3 %

Procedure:
To a mixture of 3.14 g (20 mmole) of 3-fluoro-4-nitro-phenol, 100 mL of acetonitrile and 8.3 g (60 mmole) of potassium carbonate was added 2.5 mL (21 mmole) of benzyl bromide. The mixture was heated to reflux for 1 hour, then cooled and concentrated under reduced pressure. The residue was stirred with 100 mL for 30 minutes. The solid was collected by filtration and air dried to give 4.76 g of 4-benzyloxy-2-fluoro-1-nitro-benzene as a yellow solid.
Reaction SMILES: Br[CH2:2][CH2:3][C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:14][CH3:15])[CH:10]=2)[CH:5]=1.[CH3:16][NH:17][CH:18]([N:21]1[C:27](=[O:28])[CH2:26][C:25]2[CH:29]=[C:30]([O:35][CH3:36])[C:31]([O:33][CH3:34])=[CH:32][C:24]=2[CH2:23][CH2:22]1)[CH2:19][CH3:20]>>[CH3:16][N:17]([CH:18]([N:21]1[C:27](=[O:28])[CH2:26][C:25]2[CH:29]=[C:30]([O:35][CH3:36])[C:31]([O:33][CH3:34])=[CH:32][C:24]=2[CH2:23][CH2:22]1)[CH2:19][CH3:20])[CH:3]([C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:14][CH3:15])[CH:10]=2)[CH:5]=1)[CH3:2]
Reactant: COc1ccc2cc(CCBr)ccc2c1
Reactant: CCC(NC)N1CCc2cc(OC)c(OC)cc2CC1=O
Product: CCC(N1CCc2cc(OC)c(OC)cc2CC1=O)N(C)C(C)c1ccc2cc(OC)ccc2c1
Temperature: 100 °C

Procedure:
A mixture of 0.66 g (2.5 mmol) of 2-(2-bromoethyl)-6-methoxy-naphthalene and 1.46 g (5 mmol) of 3-(N-methyl-amino-prop-3-yl)-7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one is heated to 100° C. for 90 minutes. After cooling, the crude product is purified over 70 g of aluminium oxide (neutral, activity II-III) with methylene chloride and then with increasing amounts of ethanol (up to 0.25%).
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([N:10]2[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[NH:12][C:11]2=[O:19])[CH:7]=[CH:8][CH:9]=1.[CH3:20][O:21][C:22](=[O:31])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]Br>CN(C=O)C>[CH3:20][O:21][C:22](=[O:31])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][N:12]1[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[N:10]([C:6]2[CH:7]=[CH:8][CH:9]=[C:4]([Cl:3])[CH:5]=2)[C:11]1=[O:19]
Reactant: COC(=O)CCCCCCCBr
Reactant: O=c1[nH]c2ccccc2n1-c1cccc(Cl)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)CCCCCCCn1c(=O)n(-c2cccc(Cl)c2)c2ccccc21

Procedure:
The product is produces as described in example 1 from 1.2 g. of NaH (80% suspension in mineral oil), 9.8 g. of 1-(3-chlorophenyl)-benzimidazolin-2-one, 80 cc. of DMF, 9.5 g. of 8-bromocaprylic acid methyl ester and 1.2 g. of NaJ.
Reaction SMILES: [C:1]([C:3]1[C:11]2[C:6](=[CH:7][C:8]([CH2:13][CH3:14])=[C:9]([F:12])[CH:10]=2)[NH:5][C:4]=1[C:15]1[N:20]=[CH:19][C:18]([S:21]([NH:24][C@@H:25]([CH3:30])[C:26]([F:29])([F:28])[F:27])(=[O:23])=[O:22])=[CH:17][CH:16]=1)#[N:2].Br[C:32]1[N:37]=[CH:36][CH:35]=[CH:34][N:33]=1.C(=O)([O-])[O-].[K+].[K+]>[Cu]I.CN(C=O)C>[C:1]([C:3]1[C:11]2[C:6](=[CH:7][C:8]([CH2:13][CH3:14])=[C:9]([F:12])[CH:10]=2)[N:5]([C:32]2[N:37]=[CH:36][CH:35]=[CH:34][N:33]=2)[C:4]=1[C:15]1[N:20]=[CH:19][C:18]([S:21]([NH:24][C@@H:25]([CH3:30])[C:26]([F:29])([F:27])[F:28])(=[O:22])=[O:23])=[CH:17][CH:16]=1)#[N:2]
Reactant: Brc1ncccn1
Reactant: CCc1cc2[nH]c(-c3ccc(S(=O)(=O)N[C@@H](C)C(F)(F)F)cn3)c(C#N)c2cc1F
Agent: [Cu]I
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCc1cc2c(cc1F)c(C#N)c(-c1ccc(S(=O)(=O)N[C@@H](C)C(F)(F)F)cn1)n2-c1ncccn1
Temperature: 110 °C
Reaction time: 70 h

Procedure:
A mixture of (S)-6-(3-cyano-6-ethyl-5-fluoro-1H-indol-2-yl)-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide (0.22 g, 0.5 mmol), prepared as above, 2-bromopyrimidine (0.167 g, 1.0 mmol), potassium carbonate (0.212 g, 1.5 mmol) and copper (I) iodide (20 mg, 0.1 mmol) were mixed with DMF (2.5 mL). The system was evacuated and replaced with an argon atmosphere. The reaction mixture was stirred at 110° C. for 70 hr, then cooled to 0° C., diluted with ethyl acetate and neutralized with 1N HCl. The ethyl acetate layer was washed with water, brine, dried over Na2SO4, filtrated through silica gel pad and evaporated. The crude product was triturated with CH2Cl2 and hexane and was further recrystallized from ethyl acetate and hexane. After air drying, the off-white solid (S)-6-(3-cyano-6-ethyl-5-fluoro-1-(pyrimidin-2-yl)-1H-indol-2-yl)-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide was obtained. Melting point: 195-198° C.; MS m/z 519.1 M-1-H+; 1H NMR (500 MHz, acetone-d6): □ 8.90 (1H, dd, J=2.5, 1.0 Hz), 8.83 (2H, d, J=4.5 Hz), 8.49 (1H, dd, J=8.0, 2.5 Hz), 8.16 (1 H, t, J=6.5 Hz), 8.15 (1 H, d, J=9.0 Hz), 7.68 (1 H, br s), 7.57-7.54 (2H, m), 4.32 (1 H, br s), 2.85 (2 H, q, J=7.5 Hz), 1.29 (3 H, t, J=7.5 Hz), 1.28 (3 H, d, J=7.2 Hz).
Reaction SMILES: [N:1]([CH2:4][C:5]1[CH:6]=[C:7]([CH:11]([NH:13][C:14]2[N:19]=[C:18]([C:20]3[N:24]4[CH:25]=[CH:26][CH:27]=[C:28]([CH:29]([F:31])[F:30])[C:23]4=[N:22][CH:21]=3)[C:17]([C:32]#[N:33])=[CH:16][N:15]=2)[CH3:12])[CH:8]=[CH:9][CH:10]=1)=[N+]=[N-].[H][H]>C(O)C.[C].[Pd]>[NH2:1][CH2:4][C:5]1[CH:6]=[C:7]([CH:11]([NH:13][C:14]2[N:19]=[C:18]([C:20]3[N:24]4[CH:25]=[CH:26][CH:27]=[C:28]([CH:29]([F:30])[F:31])[C:23]4=[N:22][CH:21]=3)[C:17]([C:32]#[N:33])=[CH:16][N:15]=2)[CH3:12])[CH:8]=[CH:9][CH:10]=1
Reactant: CC(Nc1ncc(C#N)c(-c2cnc3c(C(F)F)cccn23)n1)c1cccc(CN=[N+]=[N-])c1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: CC(Nc1ncc(C#N)c(-c2cnc3c(C(F)F)cccn23)n1)c1cccc(CN)c1
Yield: 92.8 %

Procedure:
87 mg of the 2-({1-[3-(azidomethyl)phenyl)ethyl}amino)-4-[8-(difluoromethyl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-5-carbonitrile [102-1] was dissolved in 3 mL of ethanol, then 50 mg of 10% palladiumcarbon catalyst was added, and stirred overnight at room temperature in a hydrogen atmosphere. The insolubles were filtered through celite, the filtrate was concentrated under reduced pressure, and 76 mg of 2-({1-[3-(aminomethyl)phenyl)ethyl}amino)-4-[8-(difluoromethyl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-5-carbonitrile [102-2] was obtained as a yellow solid.
Reaction SMILES: [K].C([O:9][C:10]1[CH:15]=[C:14]([CH2:16][CH:17]([CH3:22])[C:18](=[O:21])[CH2:19][CH3:20])[CH:13]=[CH:12][C:11]=1[N:23]1[S:27](=[O:29])(=[O:28])[NH:26][C:25](=[O:30])[CH2:24]1)C1C=CC=CC=1>CCO.O.[Pd]>[OH:9][C:10]1[CH:15]=[C:14]([CH2:16][CH:17]([CH3:22])[C:18](=[O:21])[CH2:19][CH3:20])[CH:13]=[CH:12][C:11]=1[N:23]1[S:27](=[O:29])(=[O:28])[NH:26][C:25](=[O:30])[CH2:24]1
Reactant: CCC(=O)C(C)Cc1ccc(N2CC(=O)NS2(=O)=O)c(OCc2ccccc2)c1
Agent: [Pd]
Agent: [K]
Solvent: CCO
Solvent: O
Product: CCC(=O)C(C)Cc1ccc(N2CC(=O)NS2(=O)=O)c(O)c1
Reaction time: 0.5 h

Procedure:
To a solution of 5-[2-benzyloxy-4-(2-methyl-3-oxo-pentyl)-phenyl]-1,1-dioxo-1,2,5-thiadiazolidin-3-one potassium salt in 5 mL of EtOH/water (1:1)) is added 20 mg of Degussa Pd/C and the resulting mixture is hydrogenated at 1 atm for 30 min. The catalyst is filtered through Celite and the solvent is removed under reduced pressure. The residue is purified by preparative HPLC to give the title compound: 1H NMR (Acetonitrile-d3) δ 7.30 (d, J=8.0 Hz, 1H), 6.79 (m, 1H), 6.75 (dd, J=8.0, 2.0 Hz, 1H), 4.38 (s, 2H), 2.83 (m, 2H), 2.46 (m, 2H), 2.29 (m, 1H), 1.01 (m, 3H), 0.9 (t, J=7.33 Hz, 3H). (M−1)−=325. HPLC retention time=0.92 min (Method A).
Reaction SMILES: [NH2:1][C:2]1[CH:22]=[CH:21][C:5]([O:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH3:20])=[C:14]([C:17]#[N:18])[CH:15]=3)[N:10]=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.C1(C)C=CC=CC=1.[CH2:30]([N:34]=[C:35]=[O:36])[CH2:31][CH2:32][CH3:33]>C(#N)C>[C:17]([C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][C:13]=1[O:19][CH3:20])[N:10]=[CH:9][CH:8]=[C:7]2[O:6][C:5]1[CH:21]=[CH:22][C:2]([NH:1][C:35]([NH:34][CH2:30][CH2:31][CH2:32][CH3:33])=[O:36])=[CH:3][CH:4]=1)#[N:18]
Reactant: COc1cc2nccc(Oc3ccc(N)cc3)c2cc1C#N
Reactant: CCCCN=C=O
Solvent: CC#N
Solvent: Cc1ccccc1
Product: CCCCNC(=O)Nc1ccc(Oc2ccnc3cc(OC)c(C#N)cc23)cc1
Yield: 55 %

Procedure:
4-(4-Aminophenoxy)-6-cyano-7-methoxyquinoline (150 mg) was added to 2.5 ml of toluene and 2.5 ml of acetonitrile, and the mixture was heated to reflux. After then adding n-butyl isocyanate (0.12 ml), the mixture was further heated to reflux for 1 hour. After cooling, the precipitated solid was filtered out and washed with ethyl acetate/toluene=1/1 to obtain 110 mg of the title compound as light brown crystals (55% yield).
Reaction SMILES: CCOC(/N=N/C(OCC)=O)=O.[OH:13][C:14]1[CH:21]=[CH:20][C:17]([CH:18]=[O:19])=[CH:16][CH:15]=1.[CH:22]1(O)[CH2:26][CH2:25][CH2:24][CH2:23]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[CH:22]1([O:13][C:14]2[CH:21]=[CH:20][C:17]([CH:18]=[O:19])=[CH:16][CH:15]=2)[CH2:26][CH2:25][CH2:24][CH2:23]1
Reactant: OC1CCCC1
Reactant: O=Cc1ccc(O)cc1
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: O=Cc1ccc(OC2CCCC2)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 56 %

Procedure:
To a tetrahydrofuran (250 mL) solution of diethylazodicarboxylate (16.1 mL, 40.9 mmol) were added 4-hydroxybenzaldehyde (5 g, 40.9 mmol), cyclopentanol (3.71 mL, 40.9 mmol) and triphenylphosphine (10.7 g, 40.9 mmol). This mixture was stirred for 30 minutes at room temperature. The mixture was concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (heptane:ethyl acetate=2:1) to obtain the title compound (4.36 g, 56%).
Reaction SMILES: C(N(CC)CC)C.[NH2:8][C:9]1[CH:10]=[CH:11][C:12]([O:15][C:16]2[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:18][CH:17]=2)=[N:13][CH:14]=1.[Cl:29][C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[CH:34][C:35]=1[Cl:36]>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Cl:29][C:30]1[CH:31]=[C:32]([NH:8][C:9]2[CH:10]=[CH:11][C:12]([O:15][C:16]3[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:18][CH:17]=3)=[N:13][CH:14]=2)[CH:33]=[CH:34][C:35]=1[Cl:36]
Reactant: OB(O)c1ccc(Cl)c(Cl)c1
Reactant: CCOC(=O)CCc1ccc(Oc2ccc(N)cn2)cc1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCOC(=O)CCc1ccc(Oc2ccc(Nc3ccc(Cl)c(Cl)c3)cn2)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Triethylamine (1.2 mL, 8.4 mmol) was added to a suspension of ethyl 3-(4-(5-aminopyridin-2-yloxy)phenyl)propionate (1.2 g, 4.2 mmol), 3,4-dichlorophenylboronic acid (1.6 g, 8.4 mmol), anhydrous copper acetate (0.762 g, 4.2 mmol) and molecular sieves 4A (5 g) in dichloromethane (24 mL), and the resulting reaction solution was stirred overnight at room temperature. After the resulting solution was filtered through Celite, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (n-hexane:ethyl acetate=4:1), to thereby yield 1.5 g of the title compound.
Reaction SMILES: [Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([N:9]2[C:14](=[O:15])[CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[N:11]=[C:10]2[O:20][CH3:21])=[C:4]([F:22])[CH:3]=1.[CH3:23][O:24][CH2:25]Cl.C(=O)([O-])[O-].[Na+].[Na+]>CC(C)=O>[Cl:1][C:2]1[C:7]([O:8][CH2:23][O:24][CH3:25])=[CH:6][C:5]([N:9]2[C:14](=[O:15])[CH:13]=[C:12]([C:16]([F:18])([F:17])[F:19])[N:11]=[C:10]2[O:20][CH3:21])=[C:4]([F:22])[CH:3]=1
Reactant: COc1nc(C(F)(F)F)cc(=O)n1-c1cc(O)c(Cl)cc1F
Reactant: COCCl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(C)=O
Product: COCOc1cc(-n2c(OC)nc(C(F)(F)F)cc2=O)c(F)cc1Cl

Procedure:
using 1-(4-chloro-2-fluoro-5-hydroxyphenyl)-2-methoxy-4-trifluoromethyl-6(1H)-pyrimidinone and chlorodimethyl ether with sodium carbonate in acetone there is obtained 1-[4-chloro-2-fluoro-5-(methoxymethoxy) -phenyl]-2-methoxy-4-trifluoromethyl-6(1H)-pyrimidinone, m.p. 97°-98° C.;
Reaction SMILES: [CH3:1][C:2]([CH3:17])([CH3:16])[C:3]#[C:4][C:5]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[CH:8]=[C:7]([F:14])[C:6]=1[NH2:15].N1C=CC=CC=1.[C:24](Cl)(=[O:28])[CH2:25][CH2:26][CH3:27]>C(Cl)Cl>[CH3:1][C:2]([CH3:17])([CH3:16])[C:3]#[C:4][C:5]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[CH:8]=[C:7]([F:14])[C:6]=1[NH:15][C:24](=[O:28])[CH2:25][CH2:26][CH3:27]
Reactant: CCCC(=O)Cl
Reactant: CC(C)(C)C#Cc1cc([N+](=O)[O-])cc(F)c1N
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCCC(=O)Nc1c(F)cc([N+](=O)[O-])cc1C#CC(C)(C)C
Temperature: 0 °C
Reaction time: 5 h
Yield: 61.4 %

Procedure:
To a solution of 2-(3,3-dimethyl-but-1-ynyl)-6-fluoro-4-nitro-phenylamine (4.0 g, 17 mmol) and pyridine (2.7 g, 34 mmol) in anhydrous CH2Cl2 (30 mL) was added and butyryl chloride (1.8 g, 17 mmol) dropwise at 0° C. After stirring for 5 h at 0° C., the reaction mixture was poured into ice (50 g) and extracted with CH2Cl2 (30 mL×3). The combined organic extracts were dried over anhydrous Na2SO4 and evaporated under vacuum to give N-[2-(3,3-dimethyl-but-1-ynyl)-6-fluoro-4-nitro-phenyl]-butyramide (3.2 g, 62%), which was used in the next step without further purification. 1H NMR (300 MHz, DMSO) δ 8.10 (dd, J=1.5, 2.7 Hz, 1H), 7.95 (dd, J=2.4, 9.6 Hz, 1H), 7.22 (brs, 1H), 2.45 (t, J=7.5 Hz, 2H), 1.82 (m, 2H), 1.36 (s, 9H), 1.06 (t, J=7.5 Hz, 3H).