Triphenylphosphine → (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-((2-allylphenoxy)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

HRID 921098Notes

Reaction equation

HRID 921098 reaction equation
[CH2:1]([O:4][C:5]1([CH3:34])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[N:17]=[C:18]([CH2:20][OH:21])[CH:19]=[C:15]3[N:14]=[C:13]([CH3:22])[C:12]=2[C@H:23]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:7][CH2:6]1)[CH:2]=[CH2:3].[CH2:35]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1O)[CH:36]=[CH2:37].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1.CCOCC>[CH2:1]([O:4][C:5]1([CH3:34])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[N:17]=[C:18]([CH2:20][O:21][C:39]4[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=4[CH2:35][CH:36]=[CH2:37])[CH:19]=[C:15]3[N:14]=[C:13]([CH3:22])[C:12]=2[C@H:23]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:7][CH2:6]1)[CH:2]=[CH2:3]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 156242-AllylphenolHCID 5462977Diethyl azodicarboxylateHCID 118318735(S)-Ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(hydroxymethyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

Product 1

HCID 118318772(S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-((2-allylphenoxy)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetateYield 19.77%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(hydroxymethyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.190 g, 0.320 mmol), 2-allylphenol (0.084 ml, 0.641 mmol) and Ph3P (0.126 g, 0.480 mmol) in THF (5 mL) was added DEAD (0.101 ml, 0.641 mmol) at 0° C. The reaction was slowly warming to rt over 3 h and after 1 h at rt, diluted with Et2O (50 mL), washed with water (2×10 mL), brine (10 mL), dried (MgSO4), filtered, concentrated and the resulting yellow residue purified by flash chromatography using 10 and 20% EtOAc/Hex to afford (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-((2-allylphenoxy)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.0374 g, 0.063 mmol, 19.77% yield) as colorless paste. 1H NMR (500 MHz, CDCl3) δ 7.17-7.23 (m, 2H), 7.08 (d, J=7.9 Hz, 1H), 6.94 (t, J=7.4 Hz, 1H), 6.63 (s, 1H), 6.00-6.10 (m, 2H), 5.88-5.98 (m, 1H), 5.44-5.55 (m, 1H), 5.31 (s, 2H), 5.22 (dd, J=1.3, 10.4 Hz, 1H), 4.15-4.27 (m, 2H), 4.00-4.06 (m, 2H), 3.47 (d, J=6.5 Hz, 2H), 2.62 (s, 3H), 1.88-2.06 (m, 3H), 1.68-1.77 (m, 2H), 1.37 (br. s., 3H), 1.21-1.28 (m, 12H). LCMS (M+H)=591.6.

Workup

  1. washwashed with water (2×10 mL), brine (10 mL)
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customthe resulting yellow residue purified by flash chromatography

Sources & evidence

ORD record
ord-9bf9816ac0344c2c852ec20ec566cece
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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