Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:9]2[NH:13][C:12](=[O:14])[O:11][N:10]=2)[CH:5]=[CH:6][C:7]=1[CH3:8].Br[C:16]1C=C(C=CC=1C)C(=N)NO.ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]([C:9]2[N:13]([CH3:16])[C:12](=[O:14])[O:11][N:10]=2)[CH:5]=[CH:6][C:7]=1[CH3:8]
Reactant: Cc1ccc(-c2noc(=O)[nH]2)cc1Br
Reactant: Cc1ccc(C(=N)NO)cc1Br
Agent: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: Cc1ccc(-c2noc(=O)n2C)cc1Br
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Step-2: 3-(3-Bromo-4-methylphenyl)-1,2,4-oxadiazol-5(4H)-one: To a 0° C. cooled solution of 3-bromo-N-hydroxy-4-methylbenzimidamide (500 mg, 2.18 mmol, 1.0 eq) in DCM (10 mL) was added triphosgene (250 mg, 0.87 mmol, 0.4 eq) followed by diisopropylethylamine (0.76 mL, 4.46 mmol, 2 eq). The resulting mixture was stirred at room temperature for 3 h. The reaction was cooled back down to room temperature and quenched with water (5 mL) followed by dilution with DCM. The layers were separated and the organic layer was washed with brine (10 mL), dried (Na2SO4) and filtered. The filtrate was evaporated under vacuum to afford 250 mg of the title product as white solid. 1HNMR (400 MHz, DMSO-d6) δ 13.10 (s, 1H, D2O exchangeable), 8.01 (d, J=1.5 Hz, 1H), 7.74 (dd, J=8.0, 1.5 Hz, 1H), 7.56 (d, J=8.0 Hz, 1H) 2.42 (s, 3H); ESI-MS (m/z) 255, 257 [(MH)+, Br79,81]
Reaction SMILES: [ClH:1].CC(C1C=CC=CC=1[N:11]=[C:12]([C:14]1[S:15][C:16]([S:25][CH3:26])=[C:17](N)[C:18]=1C1N=CSC=1)[NH2:13])C.Br.[CH3:28][CH:29]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[NH:37][C:38]1[S:39][CH:40]=[C:41](C2C=C(C(OC)=S)SC=2C)[N:42]=1)[CH3:30]>>[ClH:1].[CH3:30][CH:29]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[NH:37][C:38]1[S:39][CH:40]=[C:41]([C:17]2[CH:18]=[C:14]([C:12]([NH2:13])=[NH:11])[S:15][C:16]=2[S:25][CH3:26])[N:42]=1)[CH3:28]
Reactant: COC(=S)c1cc(-c2csc(Nc3ccccc3C(C)C)n2)c(C)s1
Reactant: CSc1sc(C(N)=Nc2ccccc2C(C)C)c(-c2cscn2)c1N
Agent: Br
Agent: Cl
Product: CSc1sc(C(=N)N)cc1-c1csc(Nc2ccccc2C(C)C)n1
Yield: 88 %

Procedure:
4-(2-{[2-(Methylethyl)phenyl]amino{(1,3-thiazol-4-yl))-5-methylthiothiophene-2-carboxamidine hydrochloride: Methyl 4-(2-{[2-(methylethyl)phenyl]amino}(1,3-thiazol-4-yl))-5-methylthiothiophene-2-carboxylate hydrobromide (33.1 mg, 0.06 mmol) was treated as described in Example 154, step (b) to give 22.4 mg (88%) of 4-(2-{[2-(methylethyl)phenyl]amino}(1,3-thiazol-4-yl))-5-methylthiothiophene-2-carboxamidine hydrochloride. 1H NMR (DMSO-d6, 300 MHz) δ 1.19 (d, 6H, J=6.8 Hz), 2.70 (s, 3H), 3.32 (m, 1H), 7.04 (s, 1H), 7.14-7.25 (m, 2H), 7.35 (dd, 1H, J=1.4, 7.5 Hz), 7.86 (dd, 1H, J=1.4, 7.9 Hz), 8.37 (s, 1H); Mass Spectrum (ESI) m/z calcd. for C18H20N4S3, 388.58 (M+H), found 389.2.
Reaction SMILES: [OH:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[CH:9][N:10]=2)[NH:5][C:4](=[O:19])[C:3]=1[C:20]([O:22]CC)=O.[CH:25]1([NH2:29])[CH2:28][CH2:27][CH2:26]1>C(Cl)Cl>[CH:25]1([NH:29][C:20]([C:3]2[C:4](=[O:19])[NH:5][C:6]3[C:11]([C:2]=2[OH:1])=[N:10][CH:9]=[C:8]([CH2:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:7]=3)=[O:22])[CH2:28][CH2:27][CH2:26]1
Reactant: CCOC(=O)c1c(O)c2ncc(Cc3ccccc3)cc2[nH]c1=O
Reactant: NC1CCC1
Solvent: ClCCl
Product: O=C(NC1CCC1)c1c(O)c2ncc(Cc3ccccc3)cc2[nH]c1=O

Procedure:
This compound was prepared from ethyl 4-hydroxy-2-oxo-7-(phenylmethyl)-1,2-dihydro-1,5-naphthyridine-3-carboxylate and cyclobutylamine employing methods similar to those described in Example 2 and was obtained as a white solid: 1H NMR (d6-DMSO) δ 12.00 (1H, br), 8.23 (1H, br), 7.38-7.25 (6H, m), 4.41 (1H, m, J=7.7 Hz), 4.04 (2H, br s), 2.27 (2H, br m), 1.93 (2H, br m), 1.71 (2H, br m); Anal. Calcd for C20H19N3O3.0.45 CH2Cl2: C, 63.37; H, 5.18; N, 10.84. Found: C, 63.62; H, 5.29; N, 10.97.
Reaction SMILES: [CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][C:12]([O:16][CH3:17])=[CH:13][CH:14]=2)[C@@H:9]([NH:18][C:19]2[N:24]=[CH:23][C:22]([Br:25])=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH3:26])=[O:5])[CH3:2].[H-].[Na+].[F:29][C:30]([F:44])([F:43])[C:31]1[CH:32]=[C:33]([CH:36]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:38]=1)[CH2:34]Br.O>CN(C)C=O.C(OCC)(=O)C>[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][C:12]([O:16][CH3:17])=[CH:13][CH:14]=2)[C@@H:9]([NH:18][C:19]2[N:20]=[C:21]([CH2:34][C:33]3[CH:36]=[C:37]([C:39]([F:41])([F:42])[F:40])[CH:38]=[C:31]([C:30]([F:29])([F:43])[F:44])[CH:32]=3)[C:22]([Br:25])=[CH:23][N:24]=2)[CH2:8][C@H:7]1[CH3:26])=[O:5])[CH3:2]
Reactant: FC(F)(F)c1cc(CBr)cc(C(F)(F)F)c1
Reactant: CCOC(=O)N1c2ccc(OC)nc2[C@@H](Nc2ncc(Br)cn2)C[C@H]1C
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Solvent: CCOC(C)=O
Product: CCOC(=O)N1c2ccc(OC)nc2[C@@H](Nc2ncc(Br)c(Cc3cc(C(F)(F)F)cc(C(F)(F)F)c3)n2)C[C@H]1C
Reaction time: 0.17 h

Procedure:
(2R*,4S*)-4-(5-Bromopyrimidin-2-yl)amino-6-methoxy-2-methyl-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (5.9 g) is dissolved in N,N-dimethylformamide (60 ml), then thereto is added sodium hydride(62.7%, 697 mg) at room temperature, and the mixture is stirred for 10 minutes. After adding 3,5-bis(trifluoromethyl)benzyl bromide (3.85 ml), the mixture is stirred at room temperature for 2 hours. Water and ethyl acetate is added to the reaction solution, the organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is crystallized from diisopropyl ether and hexane to give (2R*,4S*)-4-{[3,5-bis(trifluoromethyl)benzyl]-(5-bromopyrimidin-2-yl)}amino-6-methoxy-2-methyl-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (6.1 g). MS (m/z): 648/650 [M+H]+
Reaction SMILES: [Si]([O:18][C:19]1[CH:48]=[CH:47][C:22]([O:23][CH2:24][C@@H:25]([OH:46])[CH2:26][NH:27][CH2:28][CH2:29][C:30]2[CH:35]=[CH:34][C:33]([NH:36][C:37]3[C:42]([N+:43]([O-:45])=[O:44])=[CH:41][CH:40]=[CH:39][N:38]=3)=[CH:32][CH:31]=2)=[CH:21][CH:20]=1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1>C(Cl)(Cl)Cl>[OH:46][C@@H:25]([CH2:26][NH:27][CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([NH:36][C:37]2[C:42]([N+:43]([O-:45])=[O:44])=[CH:41][CH:40]=[CH:39][N:38]=2)=[CH:32][CH:31]=1)[CH2:24][O:23][C:22]1[CH:47]=[CH:48][C:19]([OH:18])=[CH:20][CH:21]=1
Reactant: CC(C)(C)[Si](Oc1ccc(OC[C@@H](O)CNCCc2ccc(Nc3ncccc3[N+](=O)[O-])cc2)cc1)(c1ccccc1)c1ccccc1
Solvent: ClC(Cl)Cl
Product: O=[N+]([O-])c1cccnc1Nc1ccc(CCNC[C@H](O)COc2ccc(O)cc2)cc1
Yield: 77.8 %

Procedure:
(2S)-1-(4-{[tert-Butyl(diphenyl)silyl]oxy}phenoxy)-3-({4-[(3-nitro-2-pyridinyl)amino]phenethyl}amino)-2-propanol (0.06 g, 0.09 mmol) was reacted according to Procedure H (eluant: 10:1 going to 5:1 chloroform) to give the title compound (0.03 g, 0.07 mmol).