Diethyl Ether → 2-methylalanyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

HRID 74772Notes

Reaction equation

HRID 74772 reaction equation
C1C2C(COC([NH:18][C:19]([CH3:66])([C:21]([NH:23][C@H:24]([C:28]([N:30]([C@@H:32]([C@@H:62]([CH3:65])[CH2:63][CH3:64])[C@H:33]([O:60][CH3:61])[CH2:34][C:35]([N:37]3[CH2:41][CH2:40][CH2:39][C@H:38]3[C@H:42]([O:58][CH3:59])[C@@H:43]([CH3:57])[C:44]([NH:46][C@H:47]([CH3:56])[C@@H:48]([OH:55])[C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)=[O:45])=[O:36])[CH3:31])=[O:29])[CH:25]([CH3:27])[CH3:26])=[O:22])[CH3:20])=O)C3C(=CC=CC=3)C=2C=CC=1.C(OCC)C.CCCCCCC>ClCCl.C(NCC)C>[CH3:20][C:19]([C:21]([NH:23][C@H:24]([C:28]([N:30]([C@@H:32]([C@@H:62]([CH3:65])[CH2:63][CH3:64])[C@H:33]([O:60][CH3:61])[CH2:34][C:35]([N:37]1[CH2:41][CH2:40][CH2:39][C@H:38]1[C@H:42]([O:58][CH3:59])[C@@H:43]([CH3:57])[C:44]([NH:46][C@H:47]([CH3:56])[C@@H:48]([OH:55])[C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)=[O:45])=[O:36])[CH3:31])=[O:29])[CH:25]([CH3:26])[CH3:27])=[O:22])([CH3:66])[NH2:18]

Participants

6

Reactant 3

HCID 3283Diethyl EtherHCID 8900HeptaneHCID 86685742HCID 86685742, compound

Product 1

HCID 715713122-methylalanyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamideYield 51%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8021DiethylamineSolvent

Procedure

According to general procedure A, from #111 (210 mg, 0.230 mmol) in dichloromethane (5 mL, 0.05 M) and diethylamine (5 mL) was synthesized the crude desired material, which was purified by silica gel chromatography (Gradient: 0% to 10% methanol in dichloromethane) to give a mixture of an oil and solid. Diethyl ether and heptane were added and the mixture was concentrated in vacuo, producing #112 (81 mg, 51%) as a white solid. LC-MS: m/z 690.4 [M+H+], retention time=1.10 minutes; HPLC (Protocol A): m/z 690.5 [M+H+], 712.4 [M+Na+], retention time=7.229 minutes (purity >90%); 1H NMR (400 MHz, DMSO-d6), presumed to be a mixture of rotamers, characteristic signals: δ [7.62 (br d, J=8 Hz), 7.88 (br d, J=8 Hz), 8.07 (br d, J=9 Hz) and 8.11 (br d, J=9 Hz), total 2H], 7.15-7.34 (m, 5H), [5.34 (d, J=4 Hz) and 5.41 (d, J=5 Hz), total 1H], 3.18, 3.21, 3.23 and 3.25 (4 s, total 6H), 2.93 and 3.08 (2 br s, total 3H), 1.15, 1.18, 1.21 and 1.25 (4 s, total 6H).

Workup

  1. customwas purified by silica gel chromatography (Gradient: 0% to 10% methanol in dichloromethane)
  2. customto give
  3. additiona mixture of an oil and solid
  4. concentrationthe mixture was concentrated in vacuo

Sources & evidence

ORD record
ord-6db879f916d34749bb0db5ae5b5aeee8
Source dataset
uspto-grants-2014_09
Patent number
US08828401B2

Reaction notes

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