Diisopropylethylamine → tert-butyl (3R)-3-{[(2S)-1-{[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[2-(cyclohepta-2,4,6-trien-1-yl)ethyl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl](methyl)amino}-3-methyl-1-oxobutan-2-yl]carbamoyl]-3-fluoropyrrolidine-1-carboxylate

HRID 74807Notes

Reaction equation

HRID 74807 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@:10]([F:16])([C:13]([O-:15])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li+].C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:51]1([CH2:58][CH2:59][NH:60][C:61](=[O:92])[C@H:62]([CH3:91])[C@H:63]([C@@H:66]2[CH2:70][CH2:69][CH2:68][N:67]2[C:71](=[O:90])[CH2:72][C@@H:73]([O:88][CH3:89])[C@@H:74]([N:79]([CH3:87])[C:80](=[O:86])[C@H:81]([CH:83]([CH3:85])[CH3:84])[NH2:82])[C@@H:75]([CH3:78])[CH2:76][CH3:77])[O:64][CH3:65])[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=[CH:52]1>ClCCl.CN(C)C=O>[CH:51]1([CH2:58][CH2:59][NH:60][C:61](=[O:92])[C@H:62]([CH3:91])[C@H:63]([C@@H:66]2[CH2:70][CH2:69][CH2:68][N:67]2[C:71](=[O:90])[CH2:72][C@@H:73]([O:88][CH3:89])[C@@H:74]([N:79]([CH3:87])[C:80](=[O:86])[C@@H:81]([NH:82][C:13]([C@@:10]2([F:16])[CH2:11][CH2:12][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:9]2)=[O:15])[CH:83]([CH3:84])[CH3:85])[C@@H:75]([CH3:78])[CH2:76][CH3:77])[O:64][CH3:65])[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=[CH:52]1

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)2×HCID 86685756lithium (3R)-1-(tert-butoxycarbonyl)-3-fluoropyrrolidine-3-carboxylateHCID 86685760N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[2-(cyclohepta-2,4,6-trien-1-yl)ethyl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

Product 1

HCID 86685761tert-butyl (3R)-3-{[(2S)-1-{[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[2-(cyclohepta-2,4,6-trien-1-yl)ethyl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl](methyl)amino}-3-methyl-1-oxobutan-2-yl]carbamoyl]-3-fluoropyrrolidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of #170 (18.2 mg, 0.076 mmol, 1 eq.) in dichloromethane (1.8 mL) and N,N-dimethylformamide (0.3 mL) was added N,N-diisopropylethylamine (0.040 mL, 0.228 mmol, 3 eq.) followed by HATU (29.2 mg, 0.076 mmol, 1 eq.). After stirring for 10 minutes at room temperature, #176 (45 mg, 0.076 mmol, 1 eq.) was added. The reaction was stirred at room temperature for 18 hours and additional HATU (29 mg, 0.076 mmol, 1 eq.) was added. After 8 hours the reaction was concentrated in vacuo to provide #183 (61.0 mg, quantitative) which was taken into the next step without further purification. LC-MS (Protocol Q1): m/z 826.6 [M+Na+], retention time=1.05 minutes.

Workup

  1. stirringThe reaction was stirred at room temperature for 18 hours
  2. concentrationAfter 8 hours the reaction was concentrated in vacuo
  3. customto provide #183 (61.0 mg, quantitative) which
  4. customwas taken into the next step without further purification

Sources & evidence

ORD record
ord-51bc318482e34ce782edf2775ded7c6a
Source dataset
uspto-grants-2014_09
Patent number
US08828401B2

Reaction notes

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