Diethyl Ether → N-methyl-L-valyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-{[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino}-3-thioxopropyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

HRID 74732Notes

Reaction equation

HRID 74732 reaction equation
C1C2C(CO[C:16]([N:18](C)[C@H:19]([C:23]([NH:25][C@H:26]([C:30]([N:32]([C@@H:34]([C@@H:67]([CH3:70])[CH2:68][CH3:69])[C@H:35]([O:65][CH3:66])[CH2:36][C:37]([N:39]3[CH2:43][CH2:42][CH2:41][C@H:40]3[C@H:44]([O:63][CH3:64])[C@@H:45]([CH3:62])[C:46]([NH:48][C@H:49]([C:57]3[S:58][CH:59]=[CH:60][N:61]=3)[CH2:50][C:51]3[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=3)=[S:47])=[O:38])[CH3:33])=[O:31])[CH:27]([CH3:29])[CH3:28])=[O:24])[CH:20]([CH3:22])[CH3:21])=O)C3C(=CC=CC=3)C=2C=CC=1.C(OCC)C.CCCCCCC>ClCCl.C(NCC)C>[CH3:16][NH:18][C@H:19]([C:23]([NH:25][C@H:26]([C:30]([N:32]([C@@H:34]([C@@H:67]([CH3:70])[CH2:68][CH3:69])[C@H:35]([O:65][CH3:66])[CH2:36][C:37]([N:39]1[CH2:43][CH2:42][CH2:41][C@H:40]1[C@H:44]([O:63][CH3:64])[C@@H:45]([CH3:62])[C:46]([NH:48][C@H:49]([C:57]1[S:58][CH:59]=[CH:60][N:61]=1)[CH2:50][C:51]1[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=1)=[S:47])=[O:38])[CH3:33])=[O:31])[CH:27]([CH3:29])[CH3:28])=[O:24])[CH:20]([CH3:22])[CH3:21]

Participants

6

Reactant 3

HCID 3283Diethyl EtherHCID 8900HeptaneHCID 86685723N-[(9H-fluoren-9-ylmethoxy)carbonyl]-N-methyl-L-valyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-{[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino}-3-thioxopropyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

Product 1

HCID 86685722N-methyl-L-valyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-{[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino}-3-thioxopropyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamideYield 92%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8021DiethylamineSolvent

Procedure

According to general procedure A, from #25 (701 mg, 0.694 mmol) in dichloromethane (10 mL, 0.07 M) and diethylamine (10 mL) was synthesized the crude desired material, which was purified by silica gel chromatography (Gradient: 0% to 10% methanol in dichloromethane) to give a glass-like solid. Diethyl ether and heptane were added and the mixture was concentrated in vacuo, producing #26 (501 mg, 92%) as a white solid. HPLC (Protocol A): m/z 787.4 [M+H+], retention time=7.229 minutes, (purity >97%); 1H NMR (400 MHz, DMSO-d6), presumed to be a mixture of rotamers, characteristic signals: δ [10.54 (br d, J=8 Hz) and 10.81 (br d, J=8. Hz), total 1H], [7.99 (br d, J=9 Hz) and 8.00 (br d, J=9 Hz), total 1H], [7.80 (d, J=3.3 Hz) and 7.83 (d, J=3.3 Hz), total 1H], [7.65 (d, J=3.2 Hz) and 7.69 (d, J=3.3 Hz), total 1H], 7.29-7.34 (m, 2H), 7.19-7.28 (m, 2H), 7.13-7.19 (m, 1H), [6.31 (ddd, J=11, 8, 4.5 Hz) and 6.45 (ddd, J=11.5, 8, 4.5 Hz), total 1H], [4.57 (dd, J=8.9, 8.7 Hz) and 4.63 (dd, J=8.7, 8.7 Hz), total 1H], 3.16, 3.21, 3.24 and 3.25 (4 s, total 6H), 2.96 and 3.03 (2 br s, total 3H), [1.14 (d, J=6.6 Hz) and 1.17 (d, J=6.4 Hz), total 3H].

Workup

  1. customwas purified by silica gel chromatography (Gradient: 0% to 10% methanol in dichloromethane)
  2. customto give a glass-like solid
  3. concentrationthe mixture was concentrated in vacuo

Sources & evidence

ORD record
ord-46e9c54b2d0647ec9bd0ada7d7245deb
Source dataset
uspto-grants-2014_09
Patent number
US08828401B2

Reaction notes

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