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

HRID 1404528Notes

Reaction equation

HRID 1404528 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). The vessel was placed on a Parr shaker and saturated with H2. After adding 45 psi H2, the vessel was shaken 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. additionAfter adding 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-04bbaf5b85664f339c7414f6f8bafbf6
Source dataset
uspto-grants-2014_12
Patent number
US08912326B2

Reaction notes

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