Diisopropylethylamine → methyl N-{(2R,3R)-3-[(2S)-1-{(3R,4S,5S)-4-[(N-{[(2S)-1-(tert-butoxycarbonyl)-2-methylpiperidin-2-yl]carbonyl}-L-valyl)(methyl)amino]-3-methoxy-5-methylheptanoyl}pyrrolidin-2-yl]-3-methoxy-2-methylpropanoyl}-L-phenylalaninate

HRID 2282884Notes

Reaction equation

HRID 2282884 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@@:9]1([CH3:17])[C:14]([OH:16])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:51][O:52][C@@H:53]([C@@H:71]1[CH2:75][CH2:74][CH2:73][N:72]1[C:76](=[O:95])[CH2:77][C@@H:78]([O:93][CH3:94])[C@@H:79]([N:84]([CH3:92])[C:85](=[O:91])[C@H:86]([CH:88]([CH3:90])[CH3:89])[NH2:87])[C@@H:80]([CH3:83])[CH2:81][CH3:82])[C@@H:54]([CH3:70])[C:55]([NH:57][C@H:58]([C:66]([O:68][CH3:69])=[O:67])[CH2:59][C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1)=[O:56]>ClCCl.CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@:9]1([C:14]([NH:87][C@H:86]([C:85]([N:84]([CH3:92])[C@@H:79]([C@@H:80]([CH3:83])[CH2:81][CH3:82])[C@H:78]([O:93][CH3:94])[CH2:77][C:76]([N:72]1[CH2:73][CH2:74][CH2:75][C@H:71]1[C@H:53]([O:52][CH3:51])[C@@H:54]([CH3:70])[C:55]([NH:57][C@H:58]([C:66]([O:68][CH3:69])=[O:67])[CH2:59][C:60]1[CH:61]=[CH:62][CH:63]=[CH:64][CH:65]=1)=[O:56])=[O:95])=[O:91])[CH:88]([CH3:89])[CH3:90])=[O:16])[CH3:17])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27281686HCID 27281686, compoundHCID 86685744methyl N-{(2R,3R)-3-methoxy-3-[(2S)-1-{(3R,4S,5S)-3-methoxy-5-methyl-4-[methyl(L-valyl)amino]heptanoyl}pyrrolidin-2-yl]-2-methylpropanoyl}-L-phenylalaninate

Product 1

HCID 86685752methyl N-{(2R,3R)-3-[(2S)-1-{(3R,4S,5S)-4-[(N-{[(2S)-1-(tert-butoxycarbonyl)-2-methylpiperidin-2-yl]carbonyl}-L-valyl)(methyl)amino]-3-methoxy-5-methylheptanoyl}pyrrolidin-2-yl]-3-methoxy-2-methylpropanoyl}-L-phenylalaninateYield 39%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of #156 (106 mg, 0.436 mmol, 1 eq.) in dichloromethane (3 mL) and N,N-dimethylformamide (0.5 mL) was added diisopropylethylamine (0.228 mL, 1.31 mmol, 3 eq.) followed by HATU (205 mg, 0.523 mmol, 1.2 eq.). The reaction was stirred for 15 minutes and #114 (276 mg, 0.436 mmol, 1 eq.) was added and stirred at room temperature for 2 hours. The reaction was diluted with dichloromethane (10 mL) and washed with 10% citric acid (3×5 mL). The organic layer was dried over sodium sulfate, filtered and the filtrate concentrated in vacuo. Purification of the residue by silica gel chromatography (Gradient: 0 to 80% acetone in heptane) afforded #160 (145 mg, 39%). LC-MS (protocol Q1): m/z 858.8 [M+H+], retention time=1.12 minutes.

Workup

  1. stirringstirred at room temperature for 2 hours
  2. washwashed with 10% citric acid (3×5 mL)
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate concentrated in vacuo
  6. customPurification of the residue by silica gel chromatography (Gradient: 0 to 80% acetone in heptane)

Sources & evidence

ORD record
ord-efeb40e4eb974f15ada8d60d0485242b
Source dataset
uspto-grants-2015_09
Patent number
US09138486B2

Reaction notes

Loading…