Tetrahydrofuran → 2-[5-(3,4-Diamino-5-tetrahydrofuran-2-yl-phenyl)pyrimidin-2-yl]propan-2-ol

HRID 869097Notes

Reaction equation

HRID 869097 reaction equation
[NH2:1][C:2]1[C:7]([CH:8]2[CH2:12][CH2:11][CH2:10][O:9]2)=[CH:6][C:5]([C:13]2[CH:14]=[N:15][C:16]([C:19]([OH:22])([CH3:21])[CH3:20])=[N:17][CH:18]=2)=[CH:4][C:3]=1[N+:23]([O-])=O.C1COCC1.CCN(CC)CC>[Pd].CO>[NH2:23][C:3]1[CH:4]=[C:5]([C:13]2[CH:18]=[N:17][C:16]([C:19]([OH:22])([CH3:20])[CH3:21])=[N:15][CH:14]=2)[CH:6]=[C:7]([CH:8]2[CH2:12][CH2:11][CH2:10][O:9]2)[C:2]=1[NH2:1]

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 681081992-[5-(4-Amino-3-nitro-5-tetrahydrofuran-2-yl-phenyl)pyrimidin-2-yl]propan-2-ol

Product 1

HCID 681083372-[5-(3,4-Diamino-5-tetrahydrofuran-2-yl-phenyl)pyrimidin-2-yl]propan-2-olYield 105.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a suspension of 2-[5-(4-amino-3-nitro-5-tetrahydrofuran-2-yl-phenyl)pyrimidin-2-yl]propan-2-ol (8) (30.10 g, 87.41 mmol) and THF (90 mL) in a Parr bottle under nitrogen was added a slurry of 5% palladium on carbon (3.01 g, 50% wet, 0.707 mmol, Aldrich 330116) in MeOH (90 mL, JT-Baker 909333), followed by NEt3 (24.37 mL, 174.8 mmol, Sigma-Aldrich 471283). Placed the vessel on a Parr shaker and saturated with H2. Added 45 psi H2 and shook until consumption was complete (HPLC showed complete conversion). The reaction mixture was purged with nitrogen, filtered through Celite™ and rinsed with EtOAc. The filtrate was re-filtered through a 0.5 micron glass fiber filter paper sandwiched between two P5 papers, and concentrated under reduced pressure giving (9) as a light brown foam (28.96 g, 98% yield; 93% NMR purity). LCMS (C18 column eluting with 10-90% CH3CN/water gradient over 5 minutes with formic acid modifier) M+1: 315.32 (1.54 min). 1H NMR (300 MHz, CDCl3) δ 8.83 (s, 2H), 6.92 (d, J=1.8 Hz, 1H), 6.88 (d, J=1.8 Hz, 1H), 4.90 (dd, J=7.9, 6.2 Hz, 1H), 4.72 (s, 1H), 4.18 (s, 2H), 4.17-4.08 (m, 1H), 3.99-3.89 (m, 1H), 3.46 (s, 2H), 2.34-2.19 (m, 1H), 2.17-2.05 (m, 3H), 1.63 (s, 6H) ppm.

Workup

  1. additionAdded 45 psi H2
  2. customThe reaction mixture was purged with nitrogen
  3. filtrationfiltered through Celite™
  4. washrinsed with EtOAc
  5. filtrationThe filtrate was re-filtered through a 0.5 micron glass fiber
  6. filtrationfilter paper
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ec74bc942e144d77a0eda3200c132b9b
Source dataset
uspto-grants-2015_03
Patent number
US08969359B2

Reaction notes

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