Acetyl chloride → HCID 21069980, compound

HRID 1372320Notes

Reaction equation

HRID 1372320 reaction equation
[NH2:1][C:2]1[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:3]=1[CH2:4][NH:5][C:6]([C:8]1[N:9]=[C:10]2[N:15]([C:16](=[O:26])[C:17]=1[O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH2:14][CH2:13][O:12][C:11]2([CH3:28])[CH3:27])=[O:7].[C:34](Cl)(=[O:36])[CH3:35].C(N(C(C)C)CC)(C)C.C([O-])(O)=O.[Na+]>O1CCCC1>[C:34]([NH:1][C:2]1[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:3]=1[CH2:4][NH:5][C:6]([C:8]1[N:9]=[C:10]2[N:15]([C:16](=[O:26])[C:17]=1[O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH2:14][CH2:13][O:12][C:11]2([CH3:28])[CH3:27])=[O:7])(=[O:36])[CH3:35]

Participants

6

Reactant 4

HCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 21069981HCID 21069981, compound

Product 1

HCID 21069980HCID 21069980, compoundYield 69.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
23 °C

Procedure

To a solution of intermediate 169, N-(2-amino-4-fluorobenzyl)-3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide (0.033 g, 0.073 mmol) in dry tetrahydrofuran (10 mL) was added acetyl chloride (5.7 μL, 0.08 mmol) and diisopropylethylamine (38 μL, 0.22 mmol). The reaction mixture was stirred at 23° C. for 3 h. NaHCO3 (0.25 M, 20 mL) was then added and the organic material extracted with ethyl acetate (3×25 mL). The organic extracts were combined, dried (MgSO4) and concentrated in vacuo. The residue was purified on a Biotage system using a silica gel column with ethyl acetate:Hex (1:2 to 2:1) as eluent to afford the title compound (0.025 g, 69% yield). 1HNMR 400 MHz (MeOD) δ (ppm): 7.66 (1H, dd, J=10.5, 2.8 Hz), 7.43–7.25 (6H, m), 6.87 (1H, ddd, (dt), J=8.8, 2.6 Hz), 5.19 (2H, s), 4.47 (2H, m), 4.08 (2H, t, J=4.9 Hz), 3.99 (2H, t, J=4.9 Hz), 2.19 (3H, s), 1.62 (6H, s). LCMS (M+H)+ m/z 495.

Workup

  1. extractionthe organic material extracted with ethyl acetate (3×25 mL)
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified on a Biotage system

Sources & evidence

ORD record
ord-914b668adb404b01a750ec434a041c22
Source dataset
uspto-grants-2007_01
Patent number
US07157447B2

Reaction notes

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