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

HRID 921086Notes

Reaction equation

HRID 921086 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].[CH2:37]([O:40][C:41]1([C:47]#[CH:48])[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]1)[CH:38]=[CH2:39].O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+]>CO>[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:48]=[C:47]([C:41]5([O:40][CH2:37][CH:38]=[CH2:39])[CH2:42][CH2:43][CH2:44][CH2:45][CH2:46]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

5

Reactant 3

HCID 11051992Cyclohexane, 1-ethynyl-1-(2-propenyloxy)-HCID 23667548Sodium AscorbateHCID 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 118318747(S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-((4-(1-(allyloxy)cyclohexyl)-1H-1,2,3-triazol-1-yl)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetateYield 36%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture 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 (0.06 g, 0.120 mmol), 1-(allyloxy)-1-ethynylcyclohexane (0.039 g, 0.240 mmol), Cu(II)SO4.5H2O (3.00 mg, 0.012 mmol) and (+)-sodium L-ascorbate (0.024 g, 0.120 mmol) in MeOH (2 mL) was stirred for 16 h at rt. Then, purified by prep-HPLC to afford (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-((4-(1-(allyloxy)cyclohexyl)-1H-1,2,3-triazol-1-yl)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.0287 g, 0.043 mmol, 36.0% yield) as pale yellow paste. 1H NMR (500 MHz, CDCl3) δ 7.56 (s, 1H), 6.41 (s, 1H), 5.99-6.08 (m, 1H), 5.90 (br. s., 1H), 5.82 (tdd, J=5.3, 10.5, 17.2 Hz, 1H), 5.73 (s, 2H), 5.47 (d, J=16.4 Hz, 1H), 5.17-5.23 (m, 2H), 5.01-5.06 (m, 1H), 4.12-4.28 (m, 2H), 4.00-4.03 (m, 2H), 3.74 (td, J=1.5, 5.4 Hz, 2H), 2.61 (s, 3H), 1.90-2.06 (m, 6H), 1.67-1.75 (m, 4H), 1.54-1.61 (m, 1H), 1.44-1.52 (m, 2H), 1.35 (s, 3H), 1.23-1.25 (m, 12H). LCMS (M+H)=664.7.

Workup

  1. customThen, purified by prep-HPLC

Sources & evidence

ORD record
ord-cf77b18dc2c5409db45cd7ee54772c0b
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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