Triphenylphosphine → HCID 118318760, compound

HRID 921095Notes

Reaction equation

HRID 921095 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+]=[N-])[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].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCN(C(C)C)C(C)C.[CH2:65]([O:68][C:69]1[CH:74]=[CH:73][CH:72]=[CH:71][C:70]=1[CH2:75][C:76](O)=[O:77])[CH:66]=[CH2:67].C(Cl)(=O)C(Cl)=O>C(Cl)Cl.CN(C=O)C.O.C1COCC1>[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][NH:21][C:76](=[O:77])[CH2:75][C:70]4[CH:71]=[CH:72][CH:73]=[CH:74][C:69]=4[O:68][CH2:65][CH:66]=[CH2:67])[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

9

Reactant 5

HCID 11776TriphenylphosphineHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 1173566699558-25-5HCID 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 118318760HCID 118318760, compoundYield 59.9%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 21881883Oxolane--water (1/1)Solvent

Procedure

A 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 (0.072 g, 0.144 mmol) and Ph3P (0.057 g, 0.216 mmol) in 1:9 (H2O/THF, 5 mL) was stirred at 55° C. for h. Then, cooled in ice-water bath and added DIEA (0.076 ml, 0.432 mmol) followed by freshly prepared acid chloride (To a solution of 2-(2-(allyloxy)phenyl)acetic acid (0.055 g, 0.288 mmol) in CH2Cl2 (5 mL) containing cat amount of DMF was added 2M oxalyl chloride (0.288 ml, 0.576 mmol) at rt. After 1 h, the reaction was concentrated and the residue was dissolved in CH2Cl2 (5 mL) and added to the amine). After the reaction mixture was taken up in Et2O (50 mL), washed with water (2×10 mL), brine (10 mL), dried (MgSO4), filtered, concentrated and the resulting yellow residue purified by prep-HPLC to afford (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-((2-(2-(allyloxy)phenyl)acetamido)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.0559 g, 0.086 mmol, 59.9% yield) as off-white solid. 1H NMR (500 MHz, CDCl3) δ 7.28-7.30 (m, 1H), 7.23-7.27 (m, 1H), 6.96 (dt, J=1.0, 7.5 Hz, 1H), 6.89 (d, J=8.2 Hz, 1H), 6.29 (s, 1H), 6.25 (t, J=5.0 Hz, 1H), 5.92-6.06 (m, 2H), 5.88 (br. s., 1H), 5.44 (d, J=17.0 Hz, 1H), 5.33 (qd, J=1.6, 17.3 Hz, 1H), 5.17-5.21 (m, 2H), 4.60 (dd, J=3.8, 5.4 Hz, 2H), 4.56 (td, J=1.6, 5.2 Hz, 2H), 4.13-4.26 (m, 2H), 4.00 (d, J=4.9 Hz, 2H), 3.68 (s, 2H), 2.59 (s, 3H), 1.82-2.01 (m, 3H), 1.64-1.72 (m, 1H), 1.34 (s, 3H), 1.21-1.25 (m, 12H). LCMS (M+H)=648.7.

Workup

  1. concentrationthe reaction was concentrated
  2. dissolutionthe residue was dissolved in CH2Cl2 (5 mL)
  3. additionadded to the amine)
  4. washwashed with water (2×10 mL), brine (10 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customthe resulting yellow residue purified by prep-HPLC

Sources & evidence

ORD record
ord-a3f88fd755664181b708ad56f54252ed
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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