Isopropanol → HCID 44816299, compound

HRID 1697889Notes

Reaction equation

HRID 1697889 reaction equation
[CH2:1]([NH:3][C:4](=[O:34])[NH:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:13]=[C:14]([N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[C:15]3[CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18][C:16]=3[N:17]=2)=[CH:8][CH:7]=1)[CH3:2].C(O)(C(F)(F)F)=O.C(O)(C)C.C(=O)([O-])[O-]>ClCCl.C1(C)C=CC=CC=1>[CH2:1]([NH:3][C:4]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:13]=[C:14]([N:28]3[CH2:29][CH2:30][O:31][CH2:32][CH2:33]3)[C:15]3[CH2:20][NH:19][CH2:18][C:16]=3[N:17]=2)=[CH:8][CH:7]=1)=[O:34])[CH3:2]

Participants

7

Reactant 4

HCID 3776IsopropanolHCID 6422Trifluoroacetic acidHCID 19660Carbonate IonHCID 46912801HCID 46912801, compound

Product 1

HCID 44816299HCID 44816299, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

Step 3—Synthesis of d: tert-butyl 2-(4-(3-ethylureido)phenyl)-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (c, 1.74 mmol) was dissolved in dichloromethane (5 mL), then TFA (3 mL) was added. The mixture was stirred at room temperature for 2 hours. Isopropanol and toluene were added and the resulting mixture was concentrated in vacuo. The resulting residue was azeotroped with toluene two more times. Methanol and methylene chloride (4 mL each) were added to the resulting residue, then PS-carbonate (2.5-3.5 mmol N/gram resin, 1.45 g) was added. The mixture was stirred at room temperature until the pH reached >7 (˜1 hr). The mixture was filtered, the resin was washed with methanol and dichloromethane. The filtrate was concentrated to provide 1-ethyl-3-(4-(4-morpholino-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea as a free amine, which was used in the next step. An aliquot was purified by reverse-phase HPLC to give the pure desired product: 1H NMR (400 MHz, DMSO) δ 9.57 (s, 1H), 8.75 (s, 1H), 8.19 (d, J=8.9, 2H), 7.50 (d, J=8.9, 2H), 6.38-6.08 (m, 1H), 4.71 (s, 2H), 4.38 (s, 2H), 3.72 (s, 8H), 3.24-3.03 (m, 2H), 1.06 (t, J=7.2, 3H); LC-MS: m/z=+369 (M+H)+.

Workup

  1. concentrationthe resulting mixture was concentrated in vacuo
  2. customThe resulting residue was azeotroped with toluene two more times
  3. additionMethanol and methylene chloride (4 mL each) were added to the resulting residue
  4. stirringThe mixture was stirred at room temperature until the pH
  5. custom>7 (˜1 hr)
  6. filtrationThe mixture was filtered
  7. washthe resin was washed with methanol and dichloromethane
  8. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-3de7189012594c4cb5434f09ca7d12fe
Source dataset
uspto-grants-2012_04
Patent number
US08163763B2

Reaction notes

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