Water → (S)-2-(3-Aminopyrrolidin-1-yl)-9-isopropyl-N-(4-(4-methylpiperazin-1-yl)phenyl)-9H-purin-6-amine

HRID 928157Notes

Reaction equation

HRID 928157 reaction equation
[CH:1]([N:4]1[CH:12]=[N:11][C:10]2[C:5]1=[N:6][C:7]([N:27]1[CH2:31][CH2:30][C@H:29]([NH:32]C(=O)OC(C)(C)C)[CH2:28]1)=[N:8][C:9]=2[NH:13][C:14]1[CH:19]=[CH:18][C:17]([N:20]2[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]2)=[CH:16][CH:15]=1)([CH3:3])[CH3:2].C(O)(C(F)(F)F)=O.O>C(Cl)Cl>[NH2:32][C@H:29]1[CH2:30][CH2:31][N:27]([C:7]2[N:6]=[C:5]3[C:10]([N:11]=[CH:12][N:4]3[CH:1]([CH3:3])[CH3:2])=[C:9]([NH:13][C:14]3[CH:15]=[CH:16][C:17]([N:20]4[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]4)=[CH:18][CH:19]=3)[N:8]=2)[CH2:28]1

Participants

5

Reactant 3

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 118081947HCID 118081947, compound

Product 1

HCID 118073535(S)-2-(3-Aminopyrrolidin-1-yl)-9-isopropyl-N-(4-(4-methylpiperazin-1-yl)phenyl)-9H-purin-6-amineYield 111%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-tert-butyl (1-(9-isopropyl-6-((4-(4-methylpiperazin-1-yl)phenyl)amino)-9H-purin-2-yl)pyrrolidin-3-yl)carbamate (1.40 g, 2.61 mmol) in DCM (30 mL) was added TFA (2.11 mL, 21 mmol). The reaction vial was capped and stirred for 3 hr. The volatiles were then removed and methanol (50 mL) and aqueous LiOH (2 M, 20 mL) were added and the mixture stirred for 16 hr. The volatiles were removed to give a white solid residue. Water (30 mL) was added and the mixture was sonicated to give a white suspension. The solid was collected by filtration and dried to give the title product as a white solid (1.26 g, 111% yield, ˜90% purity). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.10 (br. s., 1 H) 7.76-7.94 (m, 3 H) 6.87 (d, J=8.80 Hz, 2 H) 4.60 (dt, J=13.33, 6.66 Hz, 1 H) 3.58-3.72 (m, 2 H) 3.51 (dd, J=10.64, 5.99 Hz, 2 H) 3.06 (br. s., 4 H) 2.45 (br. s., 4 H) 2.22 (s, 3 H) 1.95-2.10 (m, 2 H) 1.58-1.73 (m, 3 H) 1.50 (d, J=6.72 Hz, 6 H). m/z (APCI+) for C23H33N9 436.4 (M+H)+.

Workup

  1. customThe reaction vial was capped
  2. customThe volatiles were then removed
  3. additionmethanol (50 mL) and aqueous LiOH (2 M, 20 mL) were added
  4. stirringthe mixture stirred for 16 hr
  5. customThe volatiles were removed
  6. customto give a white solid residue
  7. customthe mixture was sonicated
  8. customto give a white suspension
  9. filtrationThe solid was collected by filtration
  10. customdried

Sources & evidence

ORD record
ord-8df2963483fe470b8291b71f2096ab3a
Source dataset
uspto-grants-2016_03
Patent number
US09290496B2

Reaction notes

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