Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]#[N:9])[CH:5]=[CH:4][N:3]=1.[CH3:10][C@H:11]1[CH2:16][N:15]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20](B3OC(C)(C)C(C)(C)O3)[CH:19]=2)[CH2:14][CH2:13][N:12]1[C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34].C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:8]([C:6]1[CH:5]=[CH:4][N:3]=[C:2]([C:22]2[CH:23]=[C:18]([CH2:17][N:15]3[CH2:14][CH2:13][N:12]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[C@@H:11]([CH3:10])[CH2:16]3)[CH:19]=[CH:20][CH:21]=2)[CH:7]=1)#[N:9]
Reactant: C[C@H]1CN(Cc2cccc(B3OC(C)(C)C(C)(C)O3)c2)CCN1C(=O)OC(C)(C)C
Reactant: N#Cc1ccnc(Cl)c1
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: O
Solvent: C1COCCO1
Product: C[C@H]1CN(Cc2cccc(-c3cc(C#N)ccn3)c2)CCN1C(=O)OC(C)(C)C
Temperature: 140 °C
Yield: 93.4 %

Procedure:
To 2-chloro-4-pyridinecarbonitrile (0.416 g, 3 mmol) was added 1,1-dimethylethyl (2S)-2-methyl-4-{[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl}-1-piperazinecarboxylate (1.499 g, 3.60 mmol) followed by K2CO3 (1.244 g, 9.00 mmol) and Pd(Ph3P)4 (0.139 g, 0.120 mmol) in 1,4-dioxane (15.00 mL) and water (5.00 mL). The mixture was heated in a microwave oven for 30 min at 140° C. The organic layer was collected and the aqueous layer was extracted once with EtOAc (3 mL). The combined organic layers were filtered, concentrated on Glas-Col, redissolved in hexane/DCM (3:1, 4 mL), loaded onto Redisep silica gel column (12 g) and purified with Combiflash chromatography. Fractions were collected and the solvent was removed under reduced pressure to afford 1.10 g (94%) of the title compound. LC-MS m/z 393 (M+H)+.
Reaction SMILES: [O:1]=[CH:2][C@H:3]([C@@H:5]([C@@H:7]([CH2:9][OH:10])[OH:8])[OH:6])[OH:4].[CH2:11](O)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(Cl)(=O)C>CC(OC)(C)C>[CH2:11]([C@@:3]([C@@H:5]([C@@H:7]([CH2:9][OH:10])[OH:8])[OH:6])([OH:4])[CH:2]=[O:1])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: O=C[C@@H](O)[C@H](O)[C@H](O)CO
Reactant: OCc1ccccc1
Solvent: COC(C)(C)C
Solvent: CC(=O)Cl
Product: O=C[C@](O)(Cc1ccccc1)[C@H](O)[C@H](O)CO
Temperature: 35 °C
Reaction time: 8 h

Procedure:
D-Arabinose (50 kg, 330.04 moles) and benzyl alcohol (132.2 kg, 4.33 equivalents) were stirred and heated to 35° C. Acetyl chloride (10.9 kg, 0.42 equivalents), keeping the temperature <45° C., then stirred 50° C. overnight. The mixture was cooled to 20° C. and diluted with MTBE (600 kg). The mixture was stirred for 0.5−5 h. The solids were collected by filtration and washed with MTBE (2×40 kg). The material was dried in a filter drier. 2-Benzyl-D-arabinose was obtained as an off-white solid, 70.9 kg (88.6%). 1H NMR (300 MHz, DMSO-d6): δ 7.32 (m, 5H), 4.76 (s, 1H), 4.66 (d, J=12 Hz, 1H), 4.59 (m, 3H), 4.45 (d, J =12 Hz, 1H), 3.70 (m, 4H), 3.47(dd, J=12, 3 Hz, 1H).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]2[CH:10]=[CH:9][N:8]([Si](C(C)C)(C(C)C)C(C)C)[C:5]2=[N:6][CH:7]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O>O1CCCC1>[CH3:1][C:2]1[CH:3]=[C:4]2[CH:10]=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1
Reactant: Cc1cnc2c(ccn2[Si](C(C)C)(C(C)C)C(C)C)c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: O
Product: Cc1cnc2[nH]ccc2c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To 5-Methyl-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (100, 0.160 g, 0.55 mmol) in tetrahydrofuran (3.0 mL) was added tetra-n-butylammonium fluoride (0.145 g, 0.55 mmol). The reaction was stirred for 1 hour at room temperature. The reaction was poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 3% methanol in dichloromethane to provide light yellow solid (101, 0.07 g, 95%). MS (ESI) [M+H+]+=133.2.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][N:10]=2)[N:5]=[CH:4][C:3]=1[NH-:12].ClC1C2C(=CC=CC=2)[N:17]=[CH:16]C=1[NH-].Cl.NO>>[NH:17]1[C:2]2[C:11]3[N:10]=[CH:9][CH:8]=[CH:7][C:6]=3[N:5]=[CH:4][C:3]=2[N:12]=[CH:16]1
Reactant: [NH-]c1cnc2ccccc2c1Cl
Reactant: [NH-]c1cnc2cccnc2c1Cl
Agent: Cl
Agent: NO
Product: c1cnc2c(c1)ncc1nc[nH]c12

Procedure:
In step (7) of Reaction Scheme II, an N-(4-chloro[1,5]naphthyridin-3-yl)amide or N-(4-chloroquinolin-3-yl)amide of Formula XXXII is reacted with a hydroxylamine hydrochloride of Formula R1ONH2.HCl and cyclized to provide a 1H-imidazo[4,5-c][1,5]naphthyridine or a 1H-imidazo[4,5-c]quinoline of Formula XXXIII. The reaction can be carried out using the method described in step (3) of Reaction Scheme I.
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[NH:10][CH:9]=2)[CH2:4][CH2:3]1.[C:17](Cl)(=[O:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>>[C:17]([N:10]1[C:11]2[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:8]([CH:5]2[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]2)=[CH:9]1)(=[O:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: CN1CCC(c2c[nH]c3ccccc23)CC1
Reactant: O=C(Cl)c1ccccc1
Product: CN1CCC(c2cn(C(=O)c3ccccc3)c3ccccc23)CC1

Procedure:
(28.1 mg, 88%); from 3-(1-methyl-4-piperidinyl)-1H-indole (Example 5d, 21.5 mg, 0.10 mmol) and benzoyl chloride (21.1 mg, 0.15 mmol), HRMS-FAB+ for C21H21N2O, calculated MH+ : 319.18103; found: 319.18293.
Reaction SMILES: [Br:1][C:2]1[CH:15]=[CH:14][C:5]2[NH:6][C:7](=[O:13])[N:8]([CH3:12])[S:9](=[O:11])(=[O:10])[C:4]=2[CH:3]=1.C([O-])([O-])=O.[K+].[K+].[CH3:22][Si:23]([CH2:26][CH2:27][O:28][CH2:29]Cl)([CH3:25])[CH3:24].O>CN(C=O)C>[Br:1][C:2]1[CH:15]=[CH:14][C:5]2[N:6]([CH2:29][O:28][CH2:27][CH2:26][Si:23]([CH3:25])([CH3:24])[CH3:22])[C:7](=[O:13])[N:8]([CH3:12])[S:9](=[O:10])(=[O:11])[C:4]=2[CH:3]=1
Reactant: CN1C(=O)Nc2ccc(Br)cc2S1(=O)=O
Reactant: C[Si](C)(C)CCOCCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CN1C(=O)N(COCC[Si](C)(C)C)c2ccc(Br)cc2S1(=O)=O
Temperature: 75 °C
Reaction time: 4 h

Procedure:
To a solution of compound 42a (616 mg, 2.10 mmol) in DMF (5 mL) was added K2CO3 (1.0 g, 7.2 mmol) and SEM-Cl (563 μL, 3.17 mmol). The resulting mixture was stirred at 75° C. for 4 h, allowed to cool to rt and treated with water (20 mL). The reaction mixture was then extracted with DCM (3×20 mL). The combined DCM layers were dried over Na2SO4, filtered, and concentrated to obtain a residue which was purified by flash column chromatography on silica gel (0-50% EtOAc/hexanes) to obtain compound 42b. 1H-NMR (400 MHz, CDCl3) δ (ppm): 7.99 (d, J=2.0 Hz, 1H), 7.74 (dd, J=9.1, 2.5 Hz, 1H), 7.51 (d, J=9.1 Hz, 1H), 5.42 (s, 2H), 3.71-3.77 (m, 2H), 3.35 (s, 3H), 0.91-0.98 (m, 2H), 0.01 (s, 9H).
Reaction SMILES: S(Cl)(Cl)=O.[OH:5][C:6]1[N:7]=[CH:8][C:9]([C:12]([OH:14])=[O:13])=[N:10][CH:11]=1.[CH3:15]O>>[CH3:15][O:13][C:12]([C:9]1[CH:8]=[N:7][C:6]([OH:5])=[CH:11][N:10]=1)=[O:14]
Reactant: CO
Reactant: O=C(O)c1cnc(O)cn1
Solvent: O=S(Cl)Cl
Product: COC(=O)c1cnc(O)cn1
Reaction time: 0.5 h
Yield: 65 %

Procedure:
Thionyl chloride (152 mL, 2.08 mol) was added dropwise at 20° C. to methanol (5 L). After the addition was completed, the mixture was stirred at this temperature for 30 minutes. Then 5-hydroxy-pyrazine-2-carboxylic acid (100 g, 714 mmol) was added, and the mixture was heated at reflux for 2 hours. The reaction mixture was concentrated in vacuo, and the residue was recrystallised from methanol (400 mL) to give 71 g (464 mmol) of the title compound in 65% yield.
Reaction SMILES: [CH2:1]([NH:3][CH:4]1[CH2:9][CH2:8][S:7](=[O:11])(=[O:10])[C:6]2[S:12][C:13]([S:15]([NH2:18])(=[O:17])=[O:16])=[CH:14][C:5]1=2)[CH3:2].C(N(CC)CC)C.[C:26](Cl)(=[O:28])[CH3:27].C([O-])(O)=O.[Na+]>C1COCC1>[CH2:1]([N:3]([CH:4]1[CH2:9][CH2:8][S:7](=[O:10])(=[O:11])[C:6]2[S:12][C:13]([S:15]([NH2:18])(=[O:16])=[O:17])=[CH:14][C:5]1=2)[C:26](=[O:28])[CH3:27])[CH3:2]
Reactant: CCNC1CCS(=O)(=O)c2sc(S(N)(=O)=O)cc21
Reactant: CC(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CCN(C(C)=O)C1CCS(=O)(=O)c2sc(S(N)(=O)=O)cc21
Reaction time: 2 h
Yield: 81.1 %

Procedure:
To a mixture of 4-(N-ethylamino)-5,6-dihydro-4H-thieno[2,3-b]thiopyran-2-sulfonamide-7,7-dioxide (1.2 g, 0.0035 mol) in THF (30 ml) and triethylamine (1.1 ml, 0.79 g, 0.0078 mol) under N2 was added dropwise at room temperature a solution of acetyl chloride (0.26 ml, 0.28 g, 0.0036 mol) in THF (15 ml). After 2 hours, the mixture was poured into a saturated solution of NaHCO3 and extracted with ethyl acetate (3x). The organic extracts were dried, filtered and concentrated to dryness to yield 1.0 g (83%) of product.
Reaction SMILES: [NH2:1][C:2]1[S:6][CH:5]=[C:4]([C:7]#[N:8])[C:3]=1[C:9]1[NH:13][CH:12]=[N:11][N:10]=1.Cl.[O:15]=[C:16]1[CH2:25][CH2:24][C:23]2[C:18](=[CH:19][CH:20]=[CH:21][N:22]=2)[N:17]1[CH2:26][C:27](O)=[O:28]>>[C:7]([C:4]1[C:3]([C:9]2[N:13]=[CH:12][NH:11][N:10]=2)=[C:2]([NH:1][C:27](=[O:28])[CH2:26][N:17]2[C:18]3[C:23](=[N:22][CH:21]=[CH:20][CH:19]=3)[CH2:24][CH2:25][C:16]2=[O:15])[S:6][CH:5]=1)#[N:8]
Reactant: N#Cc1csc(N)c1-c1nnc[nH]1
Reactant: O=C(O)CN1C(=O)CCc2ncccc21
Agent: Cl
Product: N#Cc1csc(NC(=O)CN2C(=O)CCc3ncccc32)c1-c1nc[nH]n1

Procedure:
The title compound was synthesized according to protocol A from 5-amino-4-(4H-1,2,4-triazol-3-yl)thiophene-3-carbonitrile (69 mg, 0.364 mmol) and 2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetic acid hydrochloride (89 mg, 0.367 mmol). HPLC purification afforded desired product as a white solid. LCMS method [11], retention time=6.22 min; MS(ESI) 380.1 (MH+); 1H NMR (300 MHz, CD3OD) δ 8.52 (s, 1H), 8.28 (d, J=5.2 Hz, 1H), 7.88 (s, 1H), 7.82 (d, J=8.4 Hz, 1H), 7.55 (dd, J=8.4, 5.3 Hz, 1H), 5.01 (s, 2H), 3.37 (t, J=7.6 Hz, 2H), 2.99 (t, J=7.6 Hz, 2H).
Reaction SMILES: [Br:1][C:2]1[N:7]=[CH:6][C:5]([C:8](=[O:14])[C:9](OCC)=[O:10])=[CH:4][CH:3]=1.[BH4-].[Na+]>C(O)C.C(OCC)(=O)C>[Br:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]([OH:14])[CH2:9][OH:10])=[CH:4][CH:3]=1
Reactant: CCOC(=O)C(=O)c1ccc(Br)nc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: CCOC(C)=O
Product: OCC(O)c1ccc(Br)nc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 76.9 %

Procedure:
To a solution of ethyl (6-bromopyridin-3-yl)(oxo)acetate (1.00 g) in ethanol (20 mL) was slowly added sodium borohydride (250 mg). The reaction mixture was stirred at room temperature for 4 hr, diluted with ethyl acetate and washed with water. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated to give the title compound (650 mg, yield 77%) as a colorless oil. MS: 220 (MH+).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][NH:4][CH2:5][CH2:6][OH:7].[F:8][C:9]([F:16])([F:15])[C:10](OCC)=[O:11]>CCOCC>[F:8][C:9]([F:16])([F:15])[C:10]([NH:1][CH2:2][CH2:3][NH:4][CH2:5][CH2:6][OH:7])=[O:11]
Reactant: NCCNCCO
Reactant: CCOC(=O)C(F)(F)F
Solvent: CCOCC
Product: O=C(NCCNCCO)C(F)(F)F
Temperature: 25 °C
Reaction time: 2 h
Yield: 70.8 %

Procedure:
2-(2-aminoethylamino)ethanol (10 g, 96.01 mmol) was added via syringe to a stirred solution of ethyl trifluoroacetate (13.64 g, 96.01 mmol) in dry Et2O (30 mL) at 0° C. The resulting solution was stirred at room temperature for 2 hours by which time a white precipitate had formed. The precipitate was removed by filtration, washed with Et2O (100 mL), and dried in vacuo for 3 hours to afford the title compound (13.6 g, 100%). 1H NMR (300 MHz, CDCl3) δ (t, J=5.1 Hz, 2H), 3.45 (t, J=5.6 Hz, 2H), 2.86 (t, J=5.6 Hz, 2H), 2.78 (t, J=4.9 Hz, 2H), 2.22 (br s, 2H); mass spectrum (API-TIS) m/z 201 (M+H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][C:23]=1[Cl:24])[CH2:5][NH:6][C:7]([NH:9][C:10]1[S:11][CH:12]=[C:13]([CH2:15][O:16][CH2:17][CH2:18][S:19][CH3:20])[N:14]=1)=[O:8].ClC1C=CC=C(C(OO)=[O:33])C=1.C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][C:23]=1[Cl:24])[CH2:5][NH:6][C:7]([NH:9][C:10]1[S:11][CH:12]=[C:13]([CH2:15][O:16][CH2:17][CH2:18][S:19]([CH3:20])=[O:33])[N:14]=1)=[O:8]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CSCCOCc1csc(NC(=O)NCc2ccc(Cl)c(Cl)c2)n1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: CS(=O)CCOCc1csc(NC(=O)NCc2ccc(Cl)c(Cl)c2)n1
Temperature: 0 °C
Reaction time: 8 h
Yield: 11.6 %

Procedure:
1-(3,4-Dichlorobenzyl)-3-(4-((2-(methylthio)ethoxy)methyl)thiazol-2-yl)urea (Example 26) (0.98 mmol, 0.4 g) was dissolved in CHCl3 (10 mL) and cooled to 0° C. 3-Chloroperbenzoic acid (1 eq, 0.98 mmol, 0.17 g) was added and the mixture was stirred at room temperature overnight. LC-MS indicated the product was a mixture of sulfoxide and sulfone. Sodium bicarbonate (saturated, 10 mL) was added and the phases were separated. The aqueous phase was extracted with CH2Cl2 (2×20 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated to give an oil. Purification by preparative HPLC yielded 0.048 g of the title compound as a white solid. 1H NMR (300 MHz, CD3OD): δ 7.49-7.45 (m, 2H), 7.25 (m, 1H), 6.85 (s, 1H), 4.87 (s, 2H), 4.45 (s, 2H), 3.86 (m, 2H), 3.11-2.91 (m, 2H), 2.65 (s, 3H).
Reaction SMILES: Cl[C:2]1[N:3]=[C:4]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[C:5]2[S:10][C:9]([N:11]3[CH2:15][CH2:14][O:13][C:12]3=[O:16])=[CH:8][C:6]=2[N:7]=1.CC1(C)C(C)(C)OB([C:31]2[CH:39]=[CH:38][CH:37]=[C:36]3[C:32]=2[CH:33]=[N:34][NH:35]3)O1>>[NH:35]1[C:36]2[C:32](=[C:31]([C:2]3[N:3]=[C:4]([N:17]4[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)[C:5]4[S:10][C:9]([N:11]5[CH2:15][CH2:14][O:13][C:12]5=[O:16])=[CH:8][C:6]=4[N:7]=3)[CH:39]=[CH:38][CH:37]=2)[CH:33]=[N:34]1
Reactant: O=C1OCCN1c1cc2nc(Cl)nc(N3CCOCC3)c2s1
Reactant: CC1(C)OB(c2cccc3[nH]ncc23)OC1(C)C
Product: O=C1OCCN1c1cc2nc(-c3cccc4[nH]ncc34)nc(N3CCOCC3)c2s1

Procedure:
3-(2-Chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)oxazolidin-2-one (46 mg) was coupled to 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole via Procedure A. The product was purified by reverse phase HPLC to yield 8.6 mg of 439. MS (Q1) 423 (M)+
Reaction SMILES: [PH:1](=[O:4])([OH:3])[OH:2].[CH2:5]([C:7]([CH2:35][CH3:36])([CH:9]([OH:34])[C:10]1[N:14]=[CH:13][N:12]([C:15]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[N:11]=1)[CH3:8])[CH3:6].[Br:37][CH2:38][C:39](Br)=[O:40]>>[PH:1](=[O:2])([OH:4])[OH:3].[CH2:35]([C:7]([CH2:5][CH3:6])([CH:9]([O:34][C:39](=[O:40])[CH2:38][Br:37])[C:10]1[N:14]=[CH:13][N:12]([C:15]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[N:11]=1)[CH3:8])[CH3:36]
Reactant: CCC(C)(CC)C(O)c1ncn(C(c2ccccc2)(c2ccccc2)c2ccccc2)n1
Reactant: O=C(Br)CBr
Agent: O=[PH](O)O
Product: CCC(C)(CC)C(OC(=O)CBr)c1ncn(C(c2ccccc2)(c2ccccc2)c2ccccc2)n1
Yield: 32.3 %

Procedure:
Diethyl 3-hydroxy-3(1-trityl-1,2,4-triazol-3-yl)propane phosphonate (1.0 g, prepared as described in Example 24) was acylated with bromoacetyl bromide (0.50 g) in a manner similar to the acetylation described in Example 26. Diethyl 3(bromoacetoxy)-3(1-trityl-1,2,4-triazol-3-yl)propane phosphonate (0.40 g) was isolated as a colourless gum. NMR (CDCl3): δ 1.3(6H,t), 1.7-1.9(2H,m), 2.3(2H,m), 3.8-3.95(2H,m), 4.1(4H,m), 6.0(1H,t), 7.1-7.3(15H,m), 7.9(1H,2 xs). FAB M/S: MH+ 626,628. IR: 1746 cm -1, carbonyl.
Reaction SMILES: [Br:1][C:2]1[C:7]2[CH:8]=[CH:9][NH:10][C:6]=2[C:5]([Br:11])=[CH:4][N:3]=1.IC.[C:14](=O)([O-])[O-].[K+].[K+]>CC(C)=O>[Br:1][C:2]1[C:7]2[CH:8]=[CH:9][N:10]([CH3:14])[C:6]=2[C:5]([Br:11])=[CH:4][N:3]=1
Reactant: O=C([O-])[O-]
Reactant: Brc1ncc(Br)c2[nH]ccc12
Agent: [K+]
Solvent: CC(C)=O
Solvent: CI
Product: Cn1ccc2c(Br)ncc(Br)c21
Yield: 69.8 %

Procedure:
A mixture of 4,7-dibromo-1H-pyrrolo[3,2-c]pyridine (1.35 g), iodomethane (609 ul) and anhydrous potassium carbonate (1.35 g) in dry acetone (90 ml) was refluxed overnight. The mixture was evaporated and the residue added to ethyl acetate (60 ml) and water (60 ml). The organic layer was washed with water then brine, dried (MgSO4) and evaporated. Purification of the residue by chromatography on silica gel, eluting with dichloromethane, gave the title compound (0.99 g)
Reaction SMILES: [CH:1]1([C:7]2[CH:13]=[CH:12][C:10]([NH2:11])=[CH:9][C:8]=2[N+:14]([O-:16])=[O:15])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CCN(CC)CC.[C:24](OC(=O)C)(=[O:26])[CH3:25]>C(Cl)Cl>[CH:1]1([C:7]2[CH:13]=[CH:12][C:10]([NH:11][C:24](=[O:26])[CH3:25])=[CH:9][C:8]=2[N+:14]([O-:16])=[O:15])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: Nc1ccc(C2CCCCC2)c([N+](=O)[O-])c1
Reactant: CC(=O)OC(C)=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(=O)Nc1ccc(C2CCCCC2)c([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 92.7 %

Procedure:
To a solution of 4-cyclohexyl-3-nitro-aniline (1.54 g, 6.99 mmol) in DCM (15 mL) was added Et3N (1.9 mL, 13.63 mmol), followed by the addition of acetic anhydride (3.3 mL, 34.98 mmol). The reaction mixture was stirred at room temperature for 2 h, quenched with water, the layers separated and the organic layer was washed with 0.1N HCl, followed by washing with H2O. The organic layer was dried over MgSO4, filtered and concentrated to obtain N-(4-cyclohexyl-3-nitrophenyl)acetamide (1.7 g, 93%). 1H NMR (400 MHz, CDCl3) δ 7.91 (d, J=2.2 Hz, 1H), 7.69 (dd, J=8.6, 2.2 Hz, 1H), 7.52 (s, 1H), 7.40 (d, J=8.6 Hz, 1H), 3.01-2.87 (m, 1H), 2.22 (s, 3H), 1.95-1.78 (m, 5H), 1.42 (t, J=10.4 Hz, 4H), 1.32-1.21 (m, 1H).
Reaction SMILES: C1(C)C=CC=CC=1.S(=O)(=O)(O)O.[Cl:13][C:14]1[CH:22]=[C:21]([Cl:23])[CH:20]=[C:16]([C:17]([OH:19])=[O:18])[C:15]=1[OH:24].[C:25](OC(=O)C)(=[O:27])[CH3:26]>O>[C:25]([O:24][C:15]1[C:14]([Cl:13])=[CH:22][C:21]([Cl:23])=[CH:20][C:16]=1[C:17]([OH:19])=[O:18])(=[O:27])[CH3:26]
Reactant: O=C(O)c1cc(Cl)cc(Cl)c1O
Reactant: CC(=O)OC(C)=O
Agent: O=S(=O)(O)O
Solvent: Cc1ccccc1
Solvent: O
Product: CC(=O)Oc1c(Cl)cc(Cl)cc1C(=O)O
Temperature: 65 °C
Reaction time: 0.5 h
Yield: 82.7 %

Procedure:
A 1 L, round-bottom, three neck flask equipped with: a mechanical stirrer, a thermometer and a 125 mL dropping funnel with pressure equilibration was placed in a water bath maintained at 65° C. The following reagents were subsequently charged to the flask with an efficient stirring: 250 mL of dry toluene, 2.5 mL of concentrated sulfuric acid and 207 g of well ground, solid 3,5-dichlorosalicylic acid, which forms a mobile suspension. When the temperature of this constantly stirred mixture reached 60° C. (with the water bath temperature maintained at 65° C.) a drop-wise addition of 108 g (100 mL) of acetic anhydride was initiated and completed within 30 min. During the acetic anhydride addition the temperature of the reaction mixture was not allowed to exceed 75° C. After completing the addition, the mixture was stirred and heated to 70° C. for another 4 h. After this time, the agitation was stopped and the mixture cooled over night to room temperature. The white crystals that separated from the mixture were filtered off, washed with 2×10 mL of ice-cold toluene and vacuum dried at 50° C. to yield 206 g (82.7% yield) of 2-acetoxy-3,5-dichlorobenzoic acid. An additional 30.6 g (12.3%% yield) of the product was recovered by: concentrating the filtrate to ½ of the original volume, cooling the solution in an ice-water bath, filtering off the crystalline product and vacuum drying it at 50° C.
Reaction SMILES: [NH2:1][C:2]1[N:11]=[C:10]([NH2:12])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([N+:14]([O-])=O)[C:8]=2[Cl:13])[N:3]=1>[Pt].COCCO.C(O)C>[NH2:1][C:2]1[N:11]=[C:10]([NH2:12])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([NH2:14])[C:8]=2[Cl:13])[N:3]=1
Reactant: Nc1nc(N)c2c(Cl)c([N+](=O)[O-])ccc2n1
Agent: [Pt]
Solvent: COCCO
Solvent: CCO
Product: Nc1nc(N)c2c(Cl)c(N)ccc2n1

Procedure:
This compound was prepared in a manner analogous to that of Example 13, using 11.0 grams (0.049 mole) of 2,4-diamino-5-chloro-6-nitroquinazoline and 1.0 gram of 10% platinum on carbon in 70 mL of 2-methoxyethanol and 130 mL of ethanol, yielding 2,4,6-triamino-5-chloroquinazoline.
Reaction SMILES: [F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].I[CH3:14]>CN(C)C=O>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][N:8]2[CH3:14])=[CH:4][CH:3]=1
Reactant: Fc1ccc2cc[nH]c2c1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cn1ccc2ccc(F)cc21
Temperature: 25 °C
Reaction time: 15 h
Yield: 47.6 %

Procedure:
In an oven dried, nitrogen purged, 3 neck, 50 mL round bottom flask, 1.00 g (7.40 mmol) of 6-fluoroindole in 10 mL of dry dimethylformamide is reacted with 0.335 g (8.88 mmol) of 60% sodium hydride dispersed in mineral oil at room temperature for 4 h. 0.553 mL (8.88 mmol) of iodomethane is added and the reaction is allowed to stir at room temperature 15 h. The reaction is quenched with 50 mL of water, extracted 3×50 mL of ethyl acetate, dried (MgSO4), and concentrated. The crude product is purified by chromatography using hexanes:ethyl acetate as a solvent system to obtain 0.525 g of the title compound, 48% yield. MS, ES=; 1H NMR (DMSO-d6) δ 7.523-7.488 (m, 1H); 7.300-7.292 (m, 2H); 6.852-6.825 (m, 1H); 6.411-6.409 (m, 1H); 3.767 (s, 3H) ppm.
Reaction SMILES: O=C1[NH:7]C=C(C2C=CC(C(O)=O)=CN=2)C=C1.[F:17][C:18]([F:23])([F:22])[C:19]([OH:21])=[O:20].Cl[C:25]1[C:30]2[CH:31]=[C:32]([CH:34]3[CH2:39][CH2:38][N:37]([C:40]([C:42]4[CH:43]=[CH:44][C:45]([C:48]5[CH:53]=[CH:52][C:51](=[O:54])[NH:50][CH:49]=5)=[N:46][CH:47]=4)=[O:41])[CH2:36][CH2:35]3)[NH:33][C:29]=2[CH:28]=[CH:27][N:26]=1>>[F:17][C:18]([F:23])([F:22])[C:19]([OH:21])=[O:20].[NH2:7][C:25]1[C:30]2[CH:31]=[C:32]([CH:34]3[CH2:39][CH2:38][N:37]([C:40]([C:42]4[CH:43]=[CH:44][C:45]([C:48]5[CH:53]=[CH:52][C:51](=[O:54])[NH:50][CH:49]=5)=[N:46][CH:47]=4)=[O:41])[CH2:36][CH2:35]3)[NH:33][C:29]=2[CH:28]=[CH:27][N:26]=1
Reactant: O=C(c1ccc(-c2ccc(=O)[nH]c2)nc1)N1CCC(c2cc3c(Cl)nccc3[nH]2)CC1
Reactant: O=C(O)c1ccc(-c2ccc(=O)[nH]c2)nc1
Solvent: O=C(O)C(F)(F)F
Product: Nc1nccc2[nH]c(C3CCN(C(=O)c4ccc(-c5ccc(=O)[nH]c5)nc4)CC3)cc12

Procedure:
The title compound is prepared as described in EXAMPLE 44, parts A and B, but with 6′-oxo-1′,6′-dihydro-[2,3′]bipyridinyl-5-carboxylic acid, and 5-[4-(4-chloro-1H-pyrrolo[3,2-c]pyridin-2-yl)piperidine-1-carbonyl]-1′H-[2,3′]bipyridinyl-6′-one trifluoroacetate as starting materials, respectively. 1H NMR (d4-MeOH) δ 8.67-8.65 (m, 1H), 8.32 (dd, 1H), 8.25 (d, 1H), 7.92 (dd, 1H), 7.85 (dd, 1H), 7.40 (d, 1H), 6.94 (d, 1H), 6.68-6.63 (m, 2H), 4.85-4.70 (m, 1H), 3.99-3.82 (m, 1H), 3.42-3.03 (m, 3H), 2.24-2.06 (m, 2H), 1.88-1.68 (m, 2H). ESI MS (M+1)+: 415.