Allyl Alcohol → (2S)-Methyl 2-(7-(4-allylchroman-6-yl)-2-(2'-(allyloxy)-[1,1'-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

HRID 1400716Notes

Reaction equation

HRID 1400716 reaction equation
[CH2:1]([CH:4]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:14]3[N:19]4[N:20]=[C:21]([C:23]5[CH:24]=[C:25]([C:29]6[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=6[OH:35])[CH:26]=[CH:27][CH:28]=5)[CH:22]=[C:18]4[N:17]=[C:16]([CH3:36])[C:15]=3[C@H:37]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])[C:38]([O:40][CH3:41])=[O:39])[CH:12]=2)[O:7][CH2:6][CH2:5]1)[CH:2]=[CH2:3].[CH2:47](O)[CH:48]=[CH2:49].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[CH2:1]([CH:4]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:14]3[N:19]4[N:20]=[C:21]([C:23]5[CH:24]=[C:25]([C:29]6[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=6[O:35][CH2:49][CH:48]=[CH2:47])[CH:26]=[CH:27][CH:28]=5)[CH:22]=[C:18]4[N:17]=[C:16]([CH3:36])[C:15]=3[C@H:37]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])[C:38]([O:40][CH3:41])=[O:39])[CH:12]=2)[O:7][CH2:6][CH2:5]1)[CH:2]=[CH2:3]

Participants

6

Reactant 4

HCID 7858Allyl AlcoholHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 86710768HCID 86710768, compound

Product 1

HCID 89971576(2S)-Methyl 2-(7-(4-allylchroman-6-yl)-2-(2'-(allyloxy)-[1,1'-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetateYield 105.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (2S)-methyl 2-(7-(4-allylchroman-6-yl)-2-(2′-hydroxy-[1,1′-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.350 g, 0.567 mmol) in dry THF (12 ml) was treated sequentially with allyl alcohol (0.116 ml, 1.700 mmol), Ph3P (0.446 g, 1.700 mmol) and DEAD (0.269 ml, 1.700 mmol), and the reaction was stirred for 2 h. The reaction was concentrated, and the residue was purified by biotage (24 g SiO2, 0% (3 CV), 0-60% (15 CV), 60% (2 CV), EtOAc in hexane). The residue after concentration was taken up in Et2O (20 mL) and washed with water (2×20 mL) to remove residual allyl alcohol, then dried (MgSO4), filtered, and concentrated, affording the desired product (0.4 g, 0.6 mmol, quant.) as a viscous clear oil. 1H NMR (500 MHz, CDCl3) δ 8.11-8.04 (m, 1H), 7.90-7.84 (m, 1H), 7.58-7.36 (m, 5H), 7.35-7.29 (m, 1H), 7.06 (t, J=7.4 Hz, 1H), 7.02-6.93 (m, 2H), 6.90 (s, 1H), 6.04-5.91 (m, 1H), 5.90-5.78 (m, 1H), 5.37-5.30 (m, 4H), 5.27-5.13 (m, 4H), 5.12-5.02 (m, 2H), 4.55 (d, J=4.9 Hz, 2H), 4.30 (br. s., 2H), 3.82 (s, 3H), 2.68-2.63 (m, 3H), 1.01-0.93 (m, 9H). LCMS (M+H)=658.6.

Workup

  1. concentrationThe reaction was concentrated
  2. customthe residue was purified by biotage (24 g SiO2, 0% (3 CV), 0-60% (15 CV), 60% (2 CV), EtOAc in hexane)
  3. concentrationThe residue after concentration
  4. washwashed with water (2×20 mL)
  5. customto remove residual allyl alcohol
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-645f8df0852e4eecbdcd721e0e80999d
Source dataset
uspto-grants-2014_12
Patent number
US08906929B2

Reaction notes

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