Sodium Nitrite → HCID 178461657, compound

HRID 2046002Notes

Reaction equation

HRID 2046002 reaction equation
N[C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([C@@H:14]([N:16]3[CH2:21][CH2:20][C@@:19]([C:26]4[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=4)([CH2:22][CH2:23][CH2:24][OH:25])[O:18][C:17]3=[O:33])[CH3:15])=[CH:10][CH:9]=2)[CH:5]=[CH:4][N:3]=1.N([O-])=[O:35].[Na+]>CC(O)=O.O>[F:32][C:29]1[CH:30]=[CH:31][C:26]([C@:19]2([CH2:22][CH2:23][CH2:24][OH:25])[O:18][C:17](=[O:33])[N:16]([C@H:14]([C:11]3[CH:10]=[CH:9][C:8]([C:6]4[CH:5]=[CH:4][N:3]=[C:2]([OH:35])[N:7]=4)=[CH:13][CH:12]=3)[CH3:15])[CH2:21][CH2:20]2)=[CH:27][CH:28]=1

Participants

5

Reactant 2

HCID 23668193Sodium NitriteHCID 58109315HCID 58109315, compound

Product 1

HCID 178461657HCID 178461657, compoundYield 8%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (R)-3-((S)-1-(4-(2-aminopyrimidin-4-yl)phenyl)ethyl)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-1,3-oxazinan-2-one (40 mg, 0.089 mmol) in CH3COOH (0.3 mL) and H2O (0.13 mL) was added an aqueous solution of NaNO2 (2 mol/L, 0.5 mL) dropwise at 0° C. The reaction was stirred for 10 min at this temperature before heating at 60° C. for 3 h. After the mixture was evaporated to dryness, the mixture was adjusted pH 9 with aqueous NaHCO3 solution. The mixture was extracted with EtOAc, and the organic layer was dried and concentrated to give the residue, which was purified by preparative TLC to give (R)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-3-((S)-1-(4-(2-hydroxypyrimidin-4-yl)phenyl)ethyl)-1,3-oxazinan-2-one (3.18 mg, 8%). LC-MS Method 2 tR=0.87 min, m/z=452. 1H NMR (CD3OD): 1.19-1.23 (m, 2H), 1.48 (d, 3H), 1.82-1.86 (m, 2H), 2.05-2.41 (m, 3H), 3.01-3.10 (m, 1H), 3.37 (t, 2H), 5.50 (q, 1H), 6.90 (d, 1H), 6.95-7.02 (m, 4H), 7.18-7.22 (m, 2H), 7.00-7.05 (m, 3H), 7.21-7.24 (m, 2H), 7.80 (d, 2H).

Workup

  1. customAfter the mixture was evaporated to dryness
  2. extractionThe mixture was extracted with EtOAc
  3. customthe organic layer was dried
  4. concentrationconcentrated
  5. customto give the residue, which
  6. customwas purified by preparative TLC

Sources & evidence

ORD record
ord-654104d7bf3640019c37b98cc8934d0d
Source dataset
uspto-grants-2013_11
Patent number
US08592410B2

Reaction notes

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