Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][S:5][C:6]1[CH:7]=[C:8]([O:28][C:29]2[C:30]([CH3:35])=[N:31][CH:32]=[CH:33][CH:34]=2)[C:9]([NH:12][C:13]2[S:17][N:16]=[C:15]([C@H:18]3[CH2:22][O:21]C4(CCCCC4)[O:19]3)[N:14]=2)=[N:10][CH:11]=1.[ClH:36]>CCO>[ClH:36].[CH3:1][O:2][CH2:3][CH2:4][S:5][C:6]1[CH:7]=[C:8]([O:28][C:29]2[C:30]([CH3:35])=[N:31][CH:32]=[CH:33][CH:34]=2)[C:9]([NH:12][C:13]2[S:17][N:16]=[C:15]([C@H:18]([OH:19])[CH2:22][OH:21])[N:14]=2)=[N:10][CH:11]=1
Reactant: COCCSc1cnc(Nc2nc([C@H]3COC4(CCCCC4)O3)ns2)c(Oc2cccnc2C)c1
Agent: Cl
Solvent: CCO
Product: COCCSc1cnc(Nc2nc([C@H](O)CO)ns2)c(Oc2cccnc2C)c1
Temperature: 60 °C
Yield: 65 %

Procedure:
(S)—N-(5-(2-methoxyethylthio)-3-(2-methylpyridin-3-yloxy)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-amine (1.9 g, 3.68 mmol) was dissolved in EtOH (50 mL) and 6M HCl (3 mL) added and heated to 60° C. for 1.5 hours. The reaction was cooled to ambient temperature and partitioned between CH2Cl2 and saturated aqueous sodium bicarbonate, extracted with CH2Cl2, dried, filtered and concentrated. The residue was purified over silica gel (0 to 10% methanol in EtOAc) to afford (S)-1-(5-(5-(2-methoxyethylthio)-3-(2-methylpyridin-3-yloxy)pyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)ethane-1,2-diol hydrochloride (1.13 g, 2.39 mmol, 65.0% yield) as a white solid after HCl salt formation. Mass Spectrum (apci) m/z=436.1 (M+H−HCl).
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].[Cl-].[Al+3].[Cl-].[Cl-].[CH2:9]([CH:11]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=1)[C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH3:10]>ClCCl>[C:1]([C:22]1[CH:23]=[C:18]([CH2:17][CH:11]([CH2:9][CH3:10])[C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:19]=[CH:20][C:21]=1[O:24][CH3:25])(=[O:3])[CH3:2]
Reactant: CCOC(=O)C(CC)Cc1ccc(OC)cc1
Reactant: CC(=O)Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: CCOC(=O)C(CC)Cc1ccc(OC)c(C(C)=O)c1
Temperature: 0 °C
Reaction time: 8 h
Yield: 48.9 %

Procedure:
Under stirring and cooling with ice, acetyl chloride (1.00 mL, 14.1 mmol) wad added dropwise to a suspension of aluminum chloride (III) (1.78 g, 13.3 mmol) in dichloromethane (30 mL), and then the mixture was stirred for 30 minutes. Next, a solution of ethyl 2-ethyl-3-(4-methoxyphenyl)propanoate (2.10 g, 8.89 mmol) in dichloromethane (10 mL) was added dropwise. After stirring for 1 hour under cooling with ice, the mixture was allowed to stand overnight at room temperature. The reaction mixture was poured in ice water, the dichloro-methane layer was separated. and the aqueous layer was extracted with dichloromethane. The organic layers were combined and washed with water and brine, dried over anhydrous sodium sulfate, and then concentrated. The residue was purified by silica gel column chromatography (eluent n-hexane:ethyl acetate=6:1 v/v) to afford 1.21 g (49%) of the title compound as a yellow oily product.
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:17]([O:18][CH3:19])=[CH:16][CH:15]=[C:14]2[C:10]=1[C:11]([CH3:20])=[CH:12][NH:13]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)([O-:24])C.[K+].O=O.O>CN(C)C=O.C(OCC)(=O)C>[CH2:1]([O:8][C:9]1[C:17]([O:18][CH3:19])=[CH:16][CH:15]=[C:14]2[C:10]=1[C:20](=[O:24])[CH:11]=[CH:12][NH:13]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COc1ccc2[nH]cc(C)c2c1OCc1ccccc1
Reactant: CC(C)(C)[O-]
Agent: O=O
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COc1ccc2[nH]ccc(=O)c2c1OCc1ccccc1
Yield: 10.6 %

Procedure:
4-Benzyloxy-5-methoxy-3-methylindole (3.5 g) was dissolved in dimethylformamide (40 ml), and potassium t-butoxide (3.3 g) was added to the mixture. The resulting mixture was stirred at room temperature under a stream of oxygen for 5 days, poured into water and extraction with ethyl acetate was conducted. The extract was washed with saturated saline and dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (Wako Gel C-200, 80 g). Elution with a mixed solvent of chloroform (92 parts) and methanol (8 parts) gave 5-benzyloxy-6-methoxy-4(1H)-quinolone (compound 4; 390 mg).
Reaction SMILES: [OH-].[Na+].C1(S([N:12]2[C:20]3[CH:19]=[CH:18][N:17]=[C:16]([C:21]4[N:22]=[C:23]([N:43]5[CH2:48][CH2:47][O:46][CH2:45][CH2:44]5)[C:24]5[N:29]=[C:28]([CH2:30][N:31]6[CH2:36][CH2:35][N:34]([C:37]([CH3:42])([CH3:41])[C:38]([NH2:40])=[O:39])[CH2:33][CH2:32]6)[S:27][C:25]=5[N:26]=4)[C:15]=3[CH:14]=[CH:13]2)(=O)=O)C=CC=CC=1>O1CCOCC1>[CH3:42][C:37]([N:34]1[CH2:33][CH2:32][N:31]([CH2:30][C:28]2[S:27][C:25]3[N:26]=[C:21]([C:16]4[C:15]5[CH:14]=[CH:13][NH:12][C:20]=5[CH:19]=[CH:18][N:17]=4)[N:22]=[C:23]([N:43]4[CH2:48][CH2:47][O:46][CH2:45][CH2:44]4)[C:24]=3[N:29]=2)[CH2:36][CH2:35]1)([CH3:41])[C:38]([NH2:40])=[O:39]
Reactant: CC(C)(C(N)=O)N1CCN(Cc2nc3c(N4CCOCC4)nc(-c4nccc5c4ccn5S(=O)(=O)c4ccccc4)nc3s2)CC1
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: CC(C)(C(N)=O)N1CCN(Cc2nc3c(N4CCOCC4)nc(-c4nccc5[nH]ccc45)nc3s2)CC1
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 23 %

Procedure:
A degassed solution of 2-[4-(7-morpholin-4-yl-5-(tributylstannanyl)thiazolo[5,4-d]pyrimidin-2-ylmethyl)piperazin-1-yl]isobutyramide (250 mg, 0.36 mmol), 1-benzenesulfonyl-4-bromo-1H-pyrrolo[3,2-c]pyridine (130 mg, 0.39 mmol), PdCl2{PtBu2(Ph-p-Nme2)}2 (26 mg, 0.036 mmol) and copper(I) thiophene-2-carboxylate (14 mg, 0.07 mmol) in 1,4-dioxane (4 mL) was subjected to microwave irradiation at 140° C. for 20 minutes. The reaction mixture was cooled to ambient temperature and loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was then washed with MeOH and the desired product was subsequently eluted using 2 M NH3 in MeOH. The product was collected and concentrated to give 2-{4-[5-(1-benzenesulfonyl-1H-pyrrolo[3,2-c]pyridin-4-yl)-7-morpholin-4-ylthiazolo[5,4-d]pyrimidin-2-ylmethyl]piperazin-1-yl}isobutyramide as a crude oil. Aqueous NaOH (12.5 M, 0 4 mL) was added to a solution of 2-{4-[5-(1-benzenesulfonyl-1H-pyrrolo[3,2-c]pyridin-4-yl)-7-morpholin-4-yl-thiazolo[5,4-d]pyrimidin-2-ylmethyl]-piperazin-1-yl}isobutyramide in 1,4-dioxane (4 mL) and IMS (4 mL). The reaction mixture was stirred at ambient temperature for 45 min, then concentrated in vacuo. The residue was dissolved in MeOH then loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was then washed with MeOH and the desired product was subsequently eluted using 2 M NH3 in MeOH. The product was collected and concentrated to afford a solid. The solid was purified by flash chromatography (Si—PPC, DCM:MeOH, 100:0 to 98:2 to 96:4) followed by reversed phase HPLC (Phenomenex Luna C-18, 20 mM Et3N in water on a gradient of 20 mM Et3N in acetonitrile 95:5 to 2:98) to afford 169 as a yellow solid (43 mg, 23%). LCMS (method E): RT=5.03 min, [M+H]+=522.2. 1H NMR (CDCl3, 400 MHz) δ 8.55 (d, J=5.6 Hz, 1 H), 7.45-7.40 (m, 2 H), 7.38 (d, J=3.3 Hz, 1 H), 7.11 (d, J=5.3 Hz, 1 H), 5.25 (d, J=5.3 Hz, 1 H), 4.53-4.42 (m, 4 H), 3.90 (m, 6 H), 2.68 (m, 4 H), 2.62 (m, 4 H), 1.25 (s, 6 H)
Reaction SMILES: [CH3:1][C:2]1[O:3][C:4]([C:8]([OH:10])=O)=[C:5]([CH3:7])[N:6]=1.O1CCCC1.C(Cl)(=O)C(Cl)=O.[NH2:22][C:23]1[CH:24]=[C:25]([CH:42]=[CH:43][CH:44]=1)[O:26][C:27]1[CH:28]=[CH:29][C:30]2[N:31]([N:33]=[C:34]([NH:36][C:37]([CH:39]3[CH2:41][CH2:40]3)=[O:38])[N:35]=2)[CH:32]=1>CN(C)C=O.CN(C)C(=O)C>[CH:39]1([C:37]([NH:36][C:34]2[N:35]=[C:30]3[CH:29]=[CH:28][C:27]([O:26][C:25]4[CH:24]=[C:23]([NH:22][C:8]([C:4]5[O:3][C:2]([CH3:1])=[N:6][C:5]=5[CH3:7])=[O:10])[CH:44]=[CH:43][CH:42]=4)=[CH:32][N:31]3[N:33]=2)=[O:38])[CH2:40][CH2:41]1
Reactant: Cc1nc(C)c(C(=O)O)o1
Reactant: Nc1cccc(Oc2ccc3nc(NC(=O)C4CC4)nn3c2)c1
Agent: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: CC(=O)N(C)C
Solvent: C1CCOC1
Product: Cc1nc(C)c(C(=O)Nc2cccc(Oc3ccc4nc(NC(=O)C5CC5)nn4c3)c2)o1
Yield: 70.8 %

Procedure:
In the same manner as in Example 18-4 and using 2,4-dimethyl-1,3-oxazole-5-carboxylic acid (127 mg, 0.904 mmol), tetrahydrofuran (8 mL), oxalyl chloride (118 μL, 1.36 mmol), N-[6-(3-aminophenoxy)[1,2,4]triazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxamide (70.0 mg, 0.226 mmol), N,N-dimethylformamide (1 drop) and N,N-dimethylacetamide (3 mL) as starting materials, the title compound (69.2 mg, 71%) was obtained as a white solid.
Reaction SMILES: [N:1]([C@@H:4]([C@H:8]([C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=1)[C:9]1[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=1)[C:5]([OH:7])=O)=[N+]=[N-].[NH2:22][C:23]1[CH:53]=[CH:52][CH:51]=[C:50]([F:54])[C:24]=1[CH2:25][CH2:26][C@H:27]1[O:32][CH2:31][C@@H:30]([CH2:33][O:34][C:35](=[O:42])[NH:36][CH2:37][C:38]([F:41])([F:40])[F:39])[N:29](C(OC(C)(C)C)=O)[CH2:28]1>>[F:21][C:18]1[CH:19]=[CH:20][C:15]([C@H:8]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=2)[C@@H:4]([C:5]([NH:22][C:23]2[CH:53]=[CH:52][CH:51]=[C:50]([F:54])[C:24]=2[CH2:25][CH2:26][C@H:27]2[O:32][CH2:31][C@@H:30]([CH2:33][O:34][C:35](=[O:42])[NH:36][CH2:37][C:38]([F:39])([F:41])[F:40])[NH:29][CH2:28]2)=[O:7])[NH:1][C:35]([O:34][CH3:33])=[O:42])=[CH:16][CH:17]=1
Reactant: CC(C)(C)OC(=O)N1C[C@@H](CCc2c(N)cccc2F)OC[C@H]1COC(=O)NCC(F)(F)F
Reactant: [N-]=[N+]=N[C@H](C(=O)O)[C@@H](c1ccncc1)c1ccc(F)cc1
Product: COC(=O)N[C@H](C(=O)Nc1cccc(F)c1CC[C@@H]1CN[C@H](COC(=O)NCC(F)(F)F)CO1)[C@@H](c1ccncc1)c1ccc(F)cc1

Procedure:
The title compound was prepared from the product of step 1 and the product of step 4 of Example 99 using the procedures given in steps 2 and 3 of Example 93 and steps 1 and 2 of Example 91. MS (ES) m/z=680 (M+H)+.