Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CS(C)=O.C(Cl)(=O)C(Cl)=O.[C:11]([O:14][C@H:15]1[C@H:20]([O:21][C:22](=[O:24])[CH3:23])[C@@H:19]([O:25][C:26](=[O:28])[CH3:27])[C@H:18]([C:29]2[CH:34]=[CH:33][C:32]([C:35]#[N:36])=[C:31]([CH2:37][C:38]3[CH:43]=[CH:42][C:41]([O:44][CH2:45][CH2:46][OH:47])=[CH:40][CH:39]=3)[CH:30]=2)[O:17][C@@H:16]1[CH2:48][O:49][C:50](=[O:52])[CH3:51])(=[O:13])[CH3:12].C(N(CC)CC)C>C(Cl)Cl.CCCCCC>[C:11]([O:14][C@H:15]1[C@H:20]([O:21][C:22](=[O:24])[CH3:23])[C@@H:19]([O:25][C:26](=[O:28])[CH3:27])[C@H:18]([C:29]2[CH:34]=[CH:33][C:32]([C:35]#[N:36])=[C:31]([CH2:37][C:38]3[CH:39]=[CH:40][C:41]([O:44][CH2:45][CH:46]=[O:47])=[CH:42][CH:43]=3)[CH:30]=2)[O:17][C@@H:16]1[CH2:48][O:49][C:50](=[O:52])[CH3:51])(=[O:13])[CH3:12]
Reactant: CC(=O)OC[C@H]1O[C@@H](c2ccc(C#N)c(Cc3ccc(OCCO)cc3)c2)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Agent: O=C(Cl)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: CCCCCC
Solvent: ClCCl
Product: CC(=O)OC[C@H]1O[C@@H](c2ccc(C#N)c(Cc3ccc(OCC=O)cc3)c2)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Reaction time: 0.08 h
Yield: 71.6 %

Procedure:
To a solution of DMSO (0.04 mL, 0.62 mmol) in dry DCM (1.0 mL) under nitrogen atmosphere, was added oxalyl chloride (0.02 mL, 0.28 mmol) at −78° C. The reaction mixture was stirred at this temperature for 5 min followed by addition of a solution of (2R,3R,4R,5S,6S)-2-(acetoxymethyl)-6-(4-cyano-3-(4-(2-hydroxyethoxy)benzyl)phenyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (140 mg, 0.24 mmol), in DCM (1 mL). The reaction mixture was stirred at −78° C. for 30 min followed by addition of triethylamine (0.16 mL, 1.20 mmol) and further stirring at same temperature for 10 min and then at r.t. for 10 min. The reaction mixture was diluted with hexane (50 mL) and filtered to remove the solids. The filterate was dried over Na2SO4 and concentrated in vacuo to afford crude title compound (100 mg, 72%) as viscous oil which was used without purification for the next step.
Reaction SMILES: Br[C:2]1[CH:24]=[CH:23][C:5]2[C:6]3[N:7]([CH:11]=[C:12]([C:14]4[N:18]([CH:19]([CH3:21])[CH3:20])[N:17]=[C:16]([NH2:22])[N:15]=4)[N:13]=3)[CH2:8][CH2:9][O:10][C:4]=2[CH:3]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH:33]1(B2OC(C)(C)C(C)(C)O2)[CH2:35][CH2:34]1>C1COCC1.O.CCOC(C)=O>[CH:33]1([C:2]2[CH:24]=[CH:23][C:5]3[C:6]4[N:7]([CH:11]=[C:12]([C:14]5[N:18]([CH:19]([CH3:21])[CH3:20])[N:17]=[C:16]([NH2:22])[N:15]=5)[N:13]=4)[CH2:8][CH2:9][O:10][C:4]=3[CH:3]=2)[CH2:35][CH2:34]1
Reactant: CC1(C)OB(C2CC2)OC1(C)C
Reactant: CC(C)n1nc(N)nc1-c1cn2c(n1)-c1ccc(Br)cc1OCC2
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Solvent: CCOC(C)=O
Product: CC(C)n1nc(N)nc1-c1cn2c(n1)-c1ccc(C3CC3)cc1OCC2
Temperature: 130 °C
Yield: 23.8 %

Procedure:
A microwave vial was charged with a solution of 5-(9-bromo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-2-yl)-1-isopropyl-1H-1,2,4-triazol-3-amine (100 mg, 0.200 mmol) in 0.500 ml THF and 0.300 mL water. To this solution was added potassium phosphate (164 mg, 0.770 mol) and cyclopropyl boronic acid pinacol ester (308 mg, 1.48 mol). The reaction suspension was degassed by bubbling nitrogen through the stirred mixture via a syringe. After several minutes the syringe was removed and Bis(ditertbutyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (20 mg, 0.026 mmol) was added and the reaction vial was quickly sealed. The sealed vial was flash heated in a microwave at 130° C. for 30 minutes. The cooled reaction was diluted with EtOAc and the organic solution was washed with water×1, saline×1 and dried (Na2SO4) before concentration in vacuo. The crude residue was purified by preparative RP-HPLC to give 16.7 mg of 431 (14% theoretical yield). 1H NMR (400 MHz, DMSO) δ 8.24 (d, J=8.3 Hz, 1H), 7.69 (s, 1H), 6.85 (d, J=8.4 Hz, 1H), 6.74 (s, 1H), 5.73 (dt, J=13.3, 6.8 Hz, 1H), 5.15 (s, 2H), 4.46 (d, J=2.3 Hz, 4H), 2.04-1.86 (m, 1H), 1.40 (d, J=6.6 Hz, 6H), 1.11-0.88 (m, 2H), 0.72 (q, J=4.9 Hz, 2H)
Reaction SMILES: C([Sn](CCCC)(CCCC)C1C=CC=CN=1)CCC.[N:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[C:26]1[N:27]=[C:28]([N:37]2[CH2:41][C@:40]3([CH:46]4[CH2:47][CH2:48][N:43]([CH2:44][CH2:45]4)[CH2:42]3)[O:39][C:38]2=[O:49])[S:29][C:30]=1C1C=CC=CN=1>>[N:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[C:26]1[N:27]=[C:28]([N:37]2[CH2:41][C@:40]3([CH:46]4[CH2:45][CH2:44][N:43]([CH2:48][CH2:47]4)[CH2:42]3)[O:39][C:38]2=[O:49])[S:29][CH:30]=1
Reactant: O=C1O[C@]2(CN3CCC2CC3)CN1c1nc(-c2ccccn2)c(-c2ccccn2)s1
Agent: CCCC[Sn](CCCC)(CCCC)c1ccccn1
Product: O=C1O[C@]2(CN3CCC2CC3)CN1c1nc(-c2ccccn2)cs1

Procedure:
The title compound was prepared by a method analogous to that described in Example 38 using 2-(tri-n-butylstannyl)pyridine. After reverse phase HPLC and conversion to the free base, the title compound, m/z 343 (MH+) and (R)-3′-(4,5-di(2-pyridyl)thiazol-2-yl)spiro[1-azabicyclo[2.2.2]octan-3,5′-oxazolidin]-2′-one, m/e 420 (MH+).
Reaction SMILES: [OH:1][CH:2]1[CH:6]([OH:7])[CH:5]([N:8]2[C:12]3[N:13]=[C:14]([S:27][CH3:28])[N:15]=[C:16]([NH:17][CH:18]4[CH2:20][CH:19]4[C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[C:11]=3[N:10]=[N:9]2)[CH2:4][CH:3]1[C:29]([NH:31][C:32]1C=CC=C[CH:33]=1)=[O:30].[CH3:38][O:39]CCN>>[OH:1][CH:2]1[CH:6]([OH:7])[CH:5]([N:8]2[C:12]3[N:13]=[C:14]([S:27][CH3:28])[N:15]=[C:16]([NH:17][CH:18]4[CH2:20][CH:19]4[C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[C:11]=3[N:10]=[N:9]2)[CH2:4][CH:3]1[C:29]([NH:31][CH2:32][CH2:33][O:39][CH3:38])=[O:30]
Reactant: COCCN
Reactant: CSc1nc(NC2CC2c2ccccc2)c2nnn(C3CC(C(=O)Nc4ccccc4)C(O)C3O)c2n1
Product: COCCNC(=O)C1CC(n2nnc3c(NC4CC4c4ccccc4)nc(SC)nc32)C(O)C1O

Procedure:
The subtitle compound was prepared by the method of example 39, step a) using the product of example 20, step b) and methyoxyethylamine.
Reaction SMILES: C([N:3]([CH2:6][CH3:7])CC)C.CCCP(=O)=O.[Br:14][C:15]1[CH:16]=C[C:18]([O:23][C:24]([F:27])([F:26])[F:25])=[C:19]([CH:22]=1)C=O.Cl.ON.C(=O)(O)[O-].[Na+]>CN(C=O)C>[Br:14][C:15]1[CH:22]=[CH:19][C:18]([O:23][C:24]([F:25])([F:26])[F:27])=[C:7]([CH:16]=1)[C:6]#[N:3]
Reactant: O=Cc1cc(Br)ccc1OC(F)(F)F
Reactant: CCN(CC)CC
Agent: CCCP(=O)=O
Agent: Cl
Agent: NO
Solvent: CN(C)C=O
Product: N#Cc1cc(Br)ccc1OC(F)(F)F
Temperature: 100 °C
Reaction time: 8 h
Yield: 86.5 %

Procedure:
Triethylamine (1.14 mL, 8.18 mmol) and propylphosphonic anhydride (cyclic trimer) (ca. 1.7 M solution in ethyl acetate, 4.8 mL, 8.18 mmol) were added in this order to a solution of 5-bromo-2-(trifluoromethoxy)benzaldehyde (2.00 g, 7.43 mmol) and hydroxyamine hydrochloride (568 mg, 8.18 mmol) in DMF (7.5 mL), and the mixture was stirred at 100° C. for 8 hours. The reaction solution was poured to a saturated sodium bicarbonate aqueous solution, followed by extraction with ethyl acetate. The obtained organic layer was washed with brine and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography [elute: hexane/ethyl acetate=100/0-98/2] to obtain the title compound (1.71 g, yield: 86%).
Reaction SMILES: S(C1C=CC(C)=CC=1)([O-])(=O)=O.[Cl:12][C:13]1[CH:35]=[C:34]([Cl:36])[CH:33]=[CH:32][C:14]=1[O:15][CH:16]([O:23][C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:25]=1[Cl:31])[CH:17](O)[C:18]([CH3:21])([CH3:20])[CH3:19].O>CS(C)=O>[Cl:12][C:13]1[CH:35]=[C:34]([Cl:36])[CH:33]=[CH:32][C:14]=1[O:15][C:16]([O:23][C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:25]=1[Cl:31])=[CH:17][C:18]([CH3:20])([CH3:21])[CH3:19]
Reactant: CC(C)(C)C(O)C(Oc1ccc(Cl)cc1Cl)Oc1ccc(Cl)cc1Cl
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Solvent: CS(C)=O
Solvent: O
Product: CC(C)(C)C=C(Oc1ccc(Cl)cc1Cl)Oc1ccc(Cl)cc1Cl
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
54.6 g (0.1 mole) of the tosylate of 1,1-bis-(2,4-dichlorophenoxy)-3,3-dimethylbutan-2-ol in 200 ml of dry dimethylsulfoxide were mixed with an equimolar amount of potassium tert.-butylate. The mixture was stirred for 30 minutes at room temperature, after which hydrolysis was effected with water, the mixture was extracted twice with the same volume of ethyl acetate, the extracts were dried and the solvent was distilled off under reduced pressure.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-])=O)=[CH:17][C:16]=2[C:24]([F:27])([F:26])[F:25])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>CO.[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([NH2:21])=[CH:17][C:16]=2[C:24]([F:27])([F:25])[F:26])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCC(Oc2ccc([N+](=O)[O-])cc2C(F)(F)F)CC1
Agent: [Pd]
Solvent: CO
Product: CC(C)(C)OC(=O)N1CCC(Oc2ccc(N)cc2C(F)(F)F)CC1
Temperature: 25 °C
Reaction time: 5 h
Yield: 80.3 %

Procedure:
To a solution of 4-(1-t-butoxycarbonylpiperidin-4-yloxy)-3-trifluoromethylnitrobenzene (2.28 g) in methanol (50 ml) was added palladium on carbon (0.20 g) and the mixture was stirred under a hydrogen atmosphere at room temperature for 5 hours. The reaction mixture was filtered and the filtrate concentrated in vacuo. The residue was purified by chromatography on a silica gel column using hexane/ethyl acetate=3/2 as an eluant to give the desired compound (1.69 g, yield 80%) as a pale red oil.
Reaction SMILES: BrC1C=CC(=O)N(CC(O)(C)C)C=1.OC(C)(C)C[C@@:17]1([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[O:22][C:21](=[O:23])[N:20]([C@H](C2C=CC(B3OC(C)(C)C(C)(C)O3)=CC=2)C)[CH2:19][CH2:18]1.C([O-])(O)=O.[Na+]>COCCOC.CCO.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:41]1([CH:17]2[O:22][C:21](=[O:23])[NH:20][CH2:19][CH2:18]2)[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1
Reactant: C[C@@H](c1ccc(B2OC(C)(C)C(C)(C)O2)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: CC(C)(O)Cn1cc(Br)ccc1=O
Agent: O=C([O-])O
Solvent: COCCOC
Solvent: CCO
Product: O=C1NCCC(c2ccccc2)O1
Temperature: 25 °C
Reaction time: 1 h
Yield: 0 %

Procedure:
To a solution of 5-bromo-1-(2-hydroxy-2-methylpropyl)pyridin-2(1H)-one (20 mg, 81.3 mmol) in DME (6 mL) was added Pd(PPh3)4 (10 mg) under nitrogen. The mixture was stirred for 1 h at rt, and a solution of (S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one (38.95 mg, 81.3 mmol) in EtOH (2 mL) and satd aq NaHCO3 (2 mL) were added. The resulting mixture was stirred at 100° C. for 2 h, quenched with water, and extracted with EtOAc. The combined organic layer was dried over anhydrous Na2SO4 and concentrated to give the crude product, which was purified by preparative TLC and preparative HPLC to afford (S)-6-(2-hydroxy-2-methylpropyl)-3-(S)-1-(4-(1-(2-hydroxy-2-methylpropyl)-6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-6-phenyl-1,3-oxazinan-2-one (6.5 mg, 15.5%). LC-MS Method 2 tR=0.99 min, m/z=519; 1H NMR (CDCl3): δ 7.60-7.57 (d, 1H), 7.43 (s, 1H), 7.36-7.26 (m, 5H), 7.15 (d, 2H), 7.01 (d, 2H), 6.70 (d, 1H), 2.85 (m, 1H), 5.69-5.66 (m, 1H), 4.13-4.09 (s, 2H), 4.05-3.98 (s, 1H), 2.89-2.86 (m, 1H), 2.44-2.36 (m, 1H), 2.28-2.16 (m, 5H), 1.58-1.53 (d, 3H), 1.33-1.30 (s, 6H), 1.19 (s, 3H), 1.12 (s, 3H).
Reaction SMILES: [Cl:1][C:2]1[C:3]([NH:13][C:14]2[N:19]=[C:18]([NH:20][CH3:21])[C:17]([C:22]([F:25])([F:24])[F:23])=[CH:16][N:15]=2)=[CH:4][C:5]([O:11][CH3:12])=[C:6]([CH:10]=1)[C:7](O)=[O:8].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:50]([NH:53][NH2:54])(=[O:52])[CH3:51].CCN(C(C)C)C(C)C>ClCCl>[C:50]([NH:53][NH:54][C:7](=[O:8])[C:6]1[CH:10]=[C:2]([Cl:1])[C:3]([NH:13][C:14]2[N:19]=[C:18]([NH:20][CH3:21])[C:17]([C:22]([F:24])([F:23])[F:25])=[CH:16][N:15]=2)=[CH:4][C:5]=1[O:11][CH3:12])(=[O:52])[CH3:51]
Reactant: CC(=O)NN
Reactant: CNc1nc(Nc2cc(OC)c(C(=O)O)cc2Cl)ncc1C(F)(F)F
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CNc1nc(Nc2cc(OC)c(C(=O)NNC(C)=O)cc2Cl)ncc1C(F)(F)F
Temperature: 25 °C
Reaction time: 18 h
Yield: 82.7 %

Procedure:
A suspension of 5-chloro-2-methoxy-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)benzoic acid (144 mg, 50% pure material, 0.19 mmol), HATU (85 mg, 0.22 mmol), acetic hydrazide (16 mg, 0.22 mmol) and DIPEA (81 uL, 0.46 mmol) in dichloromethane (4 mL) was stirred at room temperature for 18 h. The mixture was diluted with dichloromethane (10 mL) and washed with saturated aqueous NaHCO3 solution (10 mL). A solid persisted in the aqueous layer; this was filtered, washed with water and then suspended in methanol. The solid was collected by filtration and dried in a vacuum oven to afford N′-acetoyl-5-chloro-2-methoxy-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)benzohydrazide as a white solid (68 mg, 85%). This was taken through to the next step without further purification.
Reaction SMILES: [CH2:1]([C:7]1([CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])[C:19]2[CH:18]=[C:17]3[CH:20]=[C:21]([CH3:23])[CH2:22][C:16]3=[CH:15][C:14]=2[C:13]2[C:8]1=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].C([Li])CCC.C(N)(C)(C)C.[C:40]([NH:44][Si:45](C1C2C(=CC3C(CCCCCC)(CCCCCC)C4C(C=3C=2)=CC=CC=4)C=C1C)([CH3:47])[CH3:46])([CH3:43])([CH3:42])[CH3:41]>C(OCC)C>[C:40]([NH:44][Si:45]([CH:20]1[C:17]2=[CH:18][C:19]3[C:7]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6])([CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])[C:8]4[C:13]([C:14]=3[CH:15]=[C:16]2[CH:22]=[C:21]1[CH3:23])=[CH:12][CH:11]=[CH:10][CH:9]=4)([CH3:47])[CH3:46])([CH3:43])([CH3:42])[CH3:41]
Reactant: CCCCCCC1(CCCCCC)c2ccccc2-c2cc3c(cc21)C=C(C)C3
Reactant: CCCCCCC1(CCCCCC)c2ccccc2-c2cc3c(cc21)C=C(C)C3[Si](C)(C)NC(C)(C)C
Agent: [Li]CCCC
Solvent: CC(C)(C)N
Solvent: CCOCC
Product: CCCCCCC1(CCCCCC)c2ccccc2-c2cc3c(cc21)C([Si](C)(C)NC(C)(C)C)C(C)=C3
Temperature: 25 °C
Reaction time: 12 h
Yield: 88.9 %

Procedure:
In a 500 mL round flask, 9,9-dihexyl-2-methyl-3,9-dihydrocyclopenta[b]fluorene (40.0 g, 103.5 mmol) was dissolved in 320 mL of diethyl ether, and then the temperature was lowered to −78° C. Then, n-butyllithium (2.5M hexane solution, 42 mL) was slowly injected thereto, followed by stirring at room temperature for 12 hours. After volatile materials were removed by vacuum, 350 mL of n-hexane was added to the mixture to lower the reactor temperature to −78° C., followed by addition of dichlorodimethylsilane (40 g). The temperature was again raised to room temperature, followed by stirring for 24 hours, and then salts were removed through filtering. Then, volatile materials were removed by vacuum. The product was again inputted to a 500 mL round flask, and dissolved in 320 mL of diethyl ether. The temperature was lowered to −78° C., and tert-butylamine (22.7 g, 310.4 mmol) was added thereto. The temperature was raised to room temperature, followed by stirring for 12 hours, and then volatile materials were completely removed by vacuum. Then, 200 mL of n-hexane was added to dissolve the resultant material, and salts were removed through filtering. The solvent was removed, to thereby obtain 48 g of a mixture of N-tert-butyl-1-(9,9-dihexyl-2-methyl-3,9-dihydrocyclopenta[b]fluoren-3-yl)-1,1-dimethylsilanamine and N-tert-butyl-1-(9,9-dihexyl-2-methyl-1,9-dihydrocyclopenta[b]fluoren-1-yl)-1,1-dimethylsilanamine (ratio=˜1:1), (yield: 88.9%), as viscous material.
Reaction SMILES: [NH2:1][C:2]1[CH:13]=[CH:12][C:5]([CH2:6][C@@H:7]([C:9]([OH:11])=[O:10])[NH2:8])=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[CH3:18]O>C(OCC)(=O)C>[CH3:18][O:10][C:9](=[O:11])[C@H:7]([CH2:6][C:5]1[CH:4]=[CH:3][C:2]([NH2:1])=[CH:13][CH:12]=1)[NH2:8]
Reactant: Nc1ccc(C[C@H](N)C(=O)O)cc1
Reactant: CO
Solvent: CCOC(C)=O
Solvent: O=S(Cl)Cl
Product: COC(=O)[C@@H](N)Cc1ccc(N)cc1
Yield: 88.5 %

Procedure:
To a stirred solution of p-aminophenylalanine (2.05 g, 9.9 mmol) in methanol (100ml) at 0° C. was added thionyl chloride (20ml) dropwise. Upon complete addition the reaction mixture was heated under reflux. After 24 hours the reaction mixture was cooled and reduced under pressure to give a brown oil. The brown oil was taken up in ethyl acetate (200 ml) and washed with saturated sodium bicarbonate solution (200 ml). The aqueous layer was further extracted with ethyl acetate (5×200 ml) . The combined organic layer was dried over MgSO4 and reduced under pressure to yield the title compound as a brown solid (1.7 g, 88.5%).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:9]=2/[C:10](=[CH:18]/[C:19]2[NH:20][C:21]([CH3:27])=[CH:22][C:23]=2[C:24](O)=[O:25])/[C:11](=[O:17])[NH:12]3)[CH:5]=[CH:6][CH:7]=1.[CH:28]1([NH:31][C:32]([C@@H:34]2[CH2:39][CH2:38][CH2:37][NH:36][CH2:35]2)=[O:33])[CH2:30][CH2:29]1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C>[CH:28]1([NH:31][C:32]([C@@H:34]2[CH2:39][CH2:38][CH2:37][N:36]([C:24]([C:23]3[CH:22]=[C:21]([CH3:27])[NH:20][C:19]=3/[CH:18]=[C:10]3\[C:11](=[O:17])[NH:12][C:13]4[C:9]\3=[C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=3)[CH:16]=[CH:15][CH:14]=4)=[O:25])[CH2:35]2)=[O:33])[CH2:30][CH2:29]1
Reactant: Cc1cc(C(=O)O)c(/C=C2\C(=O)Nc3cccc(-c4cccc(F)c4)c32)[nH]1
Reactant: O=C(NC1CC1)[C@@H]1CCCNC1
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: ClCCCl
Product: Cc1cc(C(=O)N2CCC[C@@H](C(=O)NC3CC3)C2)c(/C=C2\C(=O)Nc3cccc(-c4cccc(F)c4)c32)[nH]1
Yield: 37.1 %

Procedure:
2-[4-(3-Fluoro-phenyl)-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-5-methyl-1H-pyrrole-3-carboxylic acid (108 mg, 0.3 mmol) was coupled with (R)-piperidine-3-carboxylic acid cyclopropylamide (69.3 mg, 1.5 eq.), HOBt (40.5 mg, 1 eq.), EDC (86 mg, 1.5 eq.) and TEA (0.06 mL) in DMF (1 mL) to give 57 mg (37%) of the titled compound.
Reaction SMILES: [N:1]1[CH:2]=[CH:3][N:4]2[CH:9]=[CH:8][C:7]([C:10]([OH:13])([CH3:12])[CH3:11])=[N:6][C:5]=12.Cl[C:15]1[CH:20]=[CH:19][N:18]=[C:17]([CH:21]([CH3:23])[CH3:22])[N:16]=1.C([O-])([O-])=O.[Cs+].[Cs+].O>O1CCOCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH:21]([C:17]1[N:18]=[C:19]([C:3]2[N:4]3[CH:9]=[CH:8][C:7]([C:10]([OH:13])([CH3:11])[CH3:12])=[N:6][C:5]3=[N:1][CH:2]=2)[CH:20]=[CH:15][N:16]=1)([CH3:23])[CH3:22]
Reactant: CC(C)c1nccc(Cl)n1
Reactant: CC(C)(O)c1ccn2ccnc2n1
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: C1COCCO1
Solvent: O
Product: CC(C)c1nccc(-c2cnc3nc(C(C)(C)O)ccn23)n1
Temperature: 100 °C
Yield: 21.4 %

Procedure:
A mixture of 2-(imidazo[1,2-α]pyrimidin-7-yl)propan-2-ol (Example 21, Step 3) (339 mg, 1.9 mmol), 4-chloro-2-isopropylpyrimidine (300 mg, 1.9 mmol), Cs2CO3 (1.25 g, 3.8 mmol) and tetrakis(triphenylphosphine)-palladium(0) (221 mg, 10 mol %) in 1,4-dioxane (10 ml) was heated at 100° C. under N2 for 18 h. Water (75 ml) was added and the organic products were extracted with CH2Cl2 (3×50 ml). The combined organic layers were concentrated under reduced pressure and then purified by column chromatography on silica, using 10% EtOH/EtOAc as eluent, to yield 2-[3-(2-isopropylpyrimidin-4-yl)imidazo[1,2-α]pyrimidin-7-yl]propan-2-ol (121 mg, 22%): 1H NMR (400 MHz, d6-DMSO) δ 10.21 (1H, d, J 8.1), 8.76 (1H, s), 8.72 (1H, d, J 6.1), 7.88 (1H, d, J 6.1), 7.66 (1H, d, J 8.1), 5.57 (1H, s), 3.24 (1H, septet, J 7.7), 1.53 (6H, s), 1.37 (6H, d, J 7.7); m/z (ES+) 298 (M+H+).
Reaction SMILES: [C:1]1([C:7]2[N:11]3[CH:12]=[CH:13][CH:14]=[N:15][C:10]3=[N:9][C:8]=2[C:16]2[CH:23]=[CH:22][C:19]([CH:20]=O)=[CH:18][CH:17]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.Cl.Cl.[CH3:33][C:34]1[CH:35]=[CH:36][C:37]([C:40]2[NH:44][N:43]=[C:42]([CH:45]3[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]3)[N:41]=2)=[N:38][CH:39]=1.C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C1COCC1.C(Cl)(Cl)Cl>[CH3:33][C:34]1[CH:35]=[CH:36][C:37]([C:40]2[NH:41][C:42]([CH:45]3[CH2:50][CH2:49][N:48]([CH2:20][C:19]4[CH:18]=[CH:17][C:16]([C:8]5[N:9]=[C:10]6[N:15]=[CH:14][CH:13]=[CH:12][N:11]6[C:7]=5[C:1]5[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=5)=[CH:23][CH:22]=4)[CH2:47][CH2:46]3)=[N:43][N:44]=2)=[N:38][CH:39]=1
Reactant: O=Cc1ccc(-c2nc3ncccn3c2-c2ccccc2)cc1
Reactant: Cc1ccc(-c2nc(C3CCNCC3)n[nH]2)nc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: CC(=O)O
Solvent: ClC(Cl)Cl
Product: Cc1ccc(-c2nnc(C3CCN(Cc4ccc(-c5nc6ncccn6c5-c5ccccc5)cc4)CC3)[nH]2)nc1
Reaction time: 0.08 h

Procedure:
To a solution of 0.110 g (0.367 mM) 4-(3-phenylimidazo[1,2-a]pyrimidin-2-yl)benzaldehyde in 3 mL of THF is added triethylamine (2 eq). The reaction mixture is stirred for 5 minutes. To this solution is added 5-methyl-2-[3-(piperidin-4-yl)-1H-1,2,4-triazol-5-yl]pyridine dihydrochloride (Intermediate D) (1.5 eq) followed by acetic acid (2.5 eq). The reaction mixture is stirred for 10 minutes. To this mixture is added NaBH(OAc)3 (6 eq) over a period of 40 minutes. The reaction mixture is stirred overnight. The reaction mixture is quenched with methanol and concentrated. The residue obtained is taken up in chloroform and washed with water, dried and concentrated. The crude is purified on a flash column chromatography to obtain the desired compound
Reaction SMILES: [CH2:1]([N:3]1[C:7]([CH:8](O)[CH2:9][CH:10]([CH3:12])[CH3:11])=[CH:6][C:5]([C:14]2[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=2)=[N:4]1)[CH3:2].[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]([N:34]([CH3:42])[CH2:35][CH2:36][C:37]([O:39]CC)=[O:38])=[O:33])=[CH:28][CH:27]=1>>[CH2:1]([N:3]1[C:7]([CH:8]([NH:25][C:26]2[CH:27]=[CH:28][C:29]([C:32]([N:34]([CH3:42])[CH2:35][CH2:36][C:37]([OH:39])=[O:38])=[O:33])=[CH:30][CH:31]=2)[CH2:9][CH:10]([CH3:12])[CH3:11])=[CH:6][C:5]([C:14]2[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=2)=[N:4]1)[CH3:2]
Reactant: CCOC(=O)CCN(C)C(=O)c1ccc(N)cc1
Reactant: CCn1nc(-c2ccc(OC(F)(F)F)cc2)cc1C(O)CC(C)C
Product: CCn1nc(-c2ccc(OC(F)(F)F)cc2)cc1C(CC(C)C)Nc1ccc(C(=O)N(C)CCC(=O)O)cc1
Yield: 3.3 %

Procedure:
Using 1-{1-ethyl-3-[4-(trifluoromethoxy)phenyl]-1H-pyrazol-5-yl}-3-methylbutan-1-ol (0.39 g) synthesized above and ethyl 3-{[(4-aminophenyl)carbonyl](methyl)amino}propanoate (0.28 g) synthesized in Example 2(2) and in the same manner as in Example 1(7), the title object compound (0.02 g, 4%) was obtained as a white solid.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][C:13]([NH2:16])=[CH:12][CH:11]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2].[N+:17]([C:20]1[CH:25]=[CH:24][C:23]([N:26]=O)=[CH:22][CH:21]=1)([O-])=O.S.[Na]>C(O)C>[NH2:17][C:20]1[CH:25]=[CH:24][C:23]([N:26]=[N:16][C:13]2[CH:14]=[CH:15][C:10]([C:7]3[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:9][CH:8]=3)=[CH:11][CH:12]=2)=[CH:22][CH:21]=1
Reactant: Nc1ccc(-c2ccc([N+](=O)[O-])cc2)cc1
Reactant: O=Nc1ccc([N+](=O)[O-])cc1
Agent: S
Agent: [Na]
Solvent: CCO
Product: Nc1ccc(N=Nc2ccc(-c3ccc([N+](=O)[O-])cc3)cc2)cc1

Procedure:
The preparation of a compound of formula XII in which m is the integer 2 and X is alkoxy and Y is p-nitrophenyl can be carried out, for example, by reacting 4-nitro-4'-aminobiphenyl with 4-nitro-nitrosobenzene, partially reducing the resulting compound with sodium hydrogen sulfide in ethanol according to Houben-Weyl XI/1, 418, to give 4-amino-4'-(p-nitrophenyl)azobenzene, diazotizing this with sodium nitrite and hydrochloric acid, coupling the diazonium salt with phenol and etherifying the resulting compound with a 1-bromoalkane in ethanol in the presence of potassium carbonate and sodium iodide.