Diisopropylethylamine → HCID 21070034, compound

HRID 348176Notes

Reaction equation

HRID 348176 reaction equation
[CH2:1]([O:8][C:9]1[C:18](=[O:19])[N:17]2[C:12]([C:13]([CH3:21])([CH3:20])[O:14][CH2:15][CH2:16]2)=[N:11][C:10]=1[C:22]([OH:24])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[S:26]1[CH:30]=[CH:29][C:28]2[CH:31]=[CH:32][CH:33]=[C:34]([CH2:35][NH2:36])[C:27]1=2.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CC#N.CN(C)C=O>[S:26]1[CH:30]=[CH:29][C:28]2[CH:31]=[CH:32][CH:33]=[C:34]([CH2:35][NH:36][C:22]([C:10]3[N:11]=[C:12]4[N:17]([C:18](=[O:19])[C:9]=3[O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH2:16][CH2:15][O:14][C:13]4([CH3:20])[CH3:21])=[O:24])[C:27]1=2

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 210698583-(Benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxylic acidHCID 21069938HCID 21069938, compound

Product 1

HCID 21070034HCID 21070034, compoundYield 220.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
23 °C

Procedure

To a solution of intermediate 27, 3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxylic acid (0.200 g, 0.60 mmol) in CH3CN:dimethylformamide (30 mL: 5 mL) was added intermediate 139, benzo[b]thiophen-7-ylmethanamine hydrochloride (0.069 g, 0.266 mmol), benzotriazole-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBOP) (0.347 g, 0.670 mmol) and diisopropylethylamine (420 μL, 2.40 mmol). The reaction mixture was stirred at 23° C. for 60 h. The solvents were then removed in vacuo and 1N HCl (50 mL) added. This was extracted with ethyl acetate (2×50 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo. The residue was purified on a Biotage system using a silica gel column with hexane:ethyl acetate (1:1) to (1:5) gradient as eluent to afford the title compound (0.279 g, 87% yield): 1H NMR (400 MHz, DMSO-d6) δ: 9.11 (1H, dd, J=5.6 Hz), 7.81 (1H, m), 7.77 (1H, d, J=5.6 Hz), 7.52 (1H, d, J=5.6 Hz), 7.48–7.26 (6H, m), 5.09 (2H, s), 4.67 (2H, d, J=5.2 Hz), 4.04 (2H, m), 3.90 (2H, m), 1.58 (6H, s), LCMS (M+H)+ m/z 476.

Workup

  1. customThe solvents were then removed in vacuo and 1N HCl (50 mL)
  2. additionadded
  3. extractionThis was extracted with ethyl acetate (2×50 mL)
  4. dry with materialThe combined organic extracts were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified on a Biotage system

Sources & evidence

ORD record
ord-fbf00f36fd3c487e93cc084ff2c689a3
Source dataset
uspto-grants-2007_02
Patent number
US07176196B2

Reaction notes

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