Diisopropylethylamine → (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-((4-(3-hydroxyphenyl)-1H-1,2,3-triazol-1-yl)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

HRID 921082Notes

Reaction equation

HRID 921082 reaction equation
[CH2:1]([O:4][C:5]1([CH3:36])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[N:17]=[C:18]([CH2:20][N:21]=[N+:22]=[N-:23])[CH:19]=[C:15]3[N:14]=[C:13]([CH3:24])[C:12]=2[C@H:25]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:7][CH2:6]1)[CH:2]=[CH2:3].[C:37]([C:39]1[CH:40]=[C:41]([OH:45])[CH:42]=[CH:43][CH:44]=1)#[CH:38].CCN(C(C)C)C(C)C>C1COCC1.CCOCC.[Cu]I>[CH2:1]([O:4][C:5]1([CH3:36])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[N:17]=[C:18]([CH2:20][N:21]4[CH:38]=[C:37]([C:39]5[CH:44]=[CH:43][CH:42]=[C:41]([OH:45])[CH:40]=5)[N:23]=[N:22]4)[CH:19]=[C:15]3[N:14]=[C:13]([CH3:24])[C:12]=2[C@H:25]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:7][CH2:6]1)[CH:2]=[CH2:3]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 139144m-EthynylphenolHCID 118318736(S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(azidomethyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

Product 1

HCID 118318750(S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-((4-(3-hydroxyphenyl)-1H-1,2,3-triazol-1-yl)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetateYield 61%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred clear yellow solution of (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(azidomethyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.070 g, 0.140 mmol), 3-ethynylphenol (0.083 g, 0.701 mmol) and DIEA (0.122 ml, 0.701 mmol) in THF (5 mL) was added CuI (0.053 g, 0.280 mmol) at rt. After 28 h, the reaction mixture was diluted with Et2O (50 mL), washed with water (2×10 mL), brine (10 mL), dried (MgSO4), filtered and concentrated to give yellow oil which was purified by prep-HPLC to afford (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-((4-(3-hydroxyphenyl)-1H-1,2,3-triazol-1-yl)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.0528 g, 0.085 mmol, 61.0% yield) as off-white solid. 1H NMR (500 MHz, CDCl3) δ 7.75-7.99 (m, 2H), 7.52 (t, J=1.8 Hz, 1H), 7.22-7.30 (m, 2H), 6.84-6.89 (m, 1H), 6.51 (s, 1H), 5.97-6.07 (m, 1H), 5.86 (br. s., 1H), 5.78 (s, 2H), 5.44 (d, J=16.7 Hz, 1H), 5.19 (dd, J=1.6, 10.4 Hz, 1H), 4.14-4.29 (m, 2H), 4.00 (d, J=4.7 Hz, 2H), 2.62 (s, 3H), 1.82-2.03 (m, 3H), 1.65-1.73 (m, 1H), 1.31 (s, 3H), 1.24 (t, J=7.1 Hz, 3H), 1.23 (s, 9H). LCMS (M+H)=618.6.

Workup

  1. washwashed with water (2×10 mL), brine (10 mL)
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give yellow oil which
  6. customwas purified by prep-HPLC

Sources & evidence

ORD record
ord-d216cbbadc124a91b8610fa80006cce9
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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