Diisopropylethylamine → 8-(6-(2,5-dihydro-1H-pyrrol-2-yl)benzo[d][1,3]dioxol-5-ylthio)-9-(3-(isopropylamino)propyl)-9H-purin-6-amine

HRID 521601Notes

Reaction equation

HRID 521601 reaction equation
[CH3:1][CH:2]([NH:4][CH2:5][CH2:6][CH2:7][N:8]1[C:17]([S:18][C:19]2[CH:24]=[C:23]3[O:25][CH2:26][O:27][C:22]3=[CH:21][C:20]=2I)=[N:16][C:10]2[C:11]([NH2:15])=[N:12][CH:13]=[N:14][C:9]1=2)[CH3:3].C([N:36]1[CH:40]=[CH:39][CH2:38][CH2:37]1)(OC(C)(C)C)=O.CCN(C(C)C)C(C)C>CN1C(=O)CCC1.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>[NH:36]1[CH2:40][CH:39]=[CH:38][CH:37]1[C:20]1[C:19]([S:18][C:17]2[N:8]([CH2:7][CH2:6][CH2:5][NH:4][CH:2]([CH3:3])[CH3:1])[C:9]3[C:10]([N:16]=2)=[C:11]([NH2:15])[N:12]=[CH:13][N:14]=3)=[CH:24][C:23]2[O:25][CH2:26][O:27][C:22]=2[CH:21]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 9549213ZelavespibHCID 10844857tert-Butyl 2,3-dihydro-1H-pyrrole-1-carboxylate

Product 1

HCID 671169188-(6-(2,5-dihydro-1H-pyrrol-2-yl)benzo[d][1,3]dioxol-5-ylthio)-9-(3-(isopropylamino)propyl)-9H-purin-6-amineYield 23%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of PU-H71 (30 mg, 0.0585 mmol) and N-Boc-2,3-dihydro-1H-pyrrole (19.8 mg, 20.2 μL, 0.117 mmol) in NMP (1.5 mL) was evacuated and back filled with nitrogen. This was repeated four times, then DIEA (15.1 mg, 21 μL, 0.117 mmol) and Pd(PPh3)4 (13.5 mg, 0.0117 mmol) were added and the reaction mixture was heated under nitrogen at 100° C. for 20 h. Solvent was removed under reduced pressure and the resulting residue was purified by preparatory TLC (CH2Cl2:MeOH—NH3 (7N), 15:1) and the resulting residue was dissolved into 2 mL of CH2Cl2:TFA (4:1) and stirred for 1 h. Solvent was removed under reduced pressure and the resulting residue was purified by preparatory TLC (CH2Cl2:MeOH—NH3 (7N), 10:1) to give 6.0 mg (23%) of DZ3-141. 1H NMR (500 MHz, CDCl3/MeOH-d4) δ 8.19 (s, 1H), 6.98 (s, 2H), 6.04 (m, 1H), 6.01 (s, 2H), 5.74 (m, 1H), 5.62 (d, J=2.0 Hz, 1H), 4.31 (t, J=6.9 Hz, 2H), 3.81-3.88 (m, 1H), 3.89-3.95 (m, 1H), 2.87 (septet, J=6.3 Hz, 1H), 2.68 (t, J=6.7 Hz, 2H), 2.14 (m, 2H), 1.15 (d, J=6.3 Hz, 6H); HRMS (ESI) m/z [M+H]+ calcd. for C22H28N7O2S, 454.2025; found. 454.2046; HPLC: method A Rt=5.27, method B Rt=2.72.

Workup

  1. additionback filled with nitrogen
  2. customSolvent was removed under reduced pressure
  3. customthe resulting residue was purified by preparatory TLC (CH2Cl2:MeOH—NH3 (7N), 15:1)
  4. dissolutionthe resulting residue was dissolved into 2 mL of CH2Cl2:TFA (4:1)
  5. customSolvent was removed under reduced pressure
  6. customthe resulting residue was purified by preparatory TLC (CH2Cl2:MeOH—NH3 (7N), 10:1)

Sources & evidence

ORD record
ord-677532de9a1a43c987bc2cfee4b743ce
Source dataset
uspto-grants-2016_05
Patent number
US09328114B2

Reaction notes

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