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Methanol → 2-Methylalanyl-N-[(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

HRID 1772386
Notes
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Reaction equation

HRID 1772386 reaction equation
[CH3:1][C:2]([C:5]([NH:7][C@H:8]([C:12]([N:14]([C@@H:16]([C@@H:48]([CH3:51])[CH2:49][CH3:50])[C@H:17]([O:46][CH3:47])[CH2:18][C:19](N1CCC[C@H]1[C@H](OC)[C@@H](C)C(N[C@@H](CC1C=CC=CC=1)C(OC)=O)=O)=[O:20])[CH3:15])=[O:13])[CH:9]([CH3:11])[CH3:10])=[O:6])([CH3:4])[NH2:3].C1C2C(COC(NC(C)(C(N[C@H](C(N([C@@H]([C@@H](C)CC)[C@H](OC)CC([N:88]3[CH2:92][CH2:91][CH2:90][C@H:89]3[C@H:93]([O:111][CH3:112])[C@@H:94]([CH3:110])[C:95]([NH:97][C@@H:98]([CH2:103][C:104]3[CH:109]=[CH:108][CH:107]=[CH:106][CH:105]=3)C(OC)=O)=[O:96])=O)C)=O)C(C)C)=O)C)=O)C3C(=CC=CC=3)C=2C=CC=1.[CH2:120](NCC)C.CO>ClCCl>[CH3:1][C:2]([C:5]([NH:7][C@H:8]([C:12]([N:14]([C@@H:16]([C@@H:48]([CH3:51])[CH2:49][CH3:50])[C@H:17]([O:46][CH3:47])[CH2:18][C:19]([N:88]1[CH2:92][CH2:91][CH2:90][C@H:89]1[C@H:93]([O:111][CH3:112])[C@@H:94]([CH3:110])[C:95]([NH:97][CH2:98][CH2:103][CH:104]1[CH:109]=[CH:108][CH:107]=[CH:106][CH:105]=[CH:120]1)=[O:96])=[O:20])[CH3:15])=[O:13])[CH:9]([CH3:11])[CH3:10])=[O:6])([CH3:4])[NH2:3]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 887MethanolHCID 8021DiethylamineHCID 715707272-methylalanyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-3-{[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]amino}-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide2×HCID 89573209
N-[(9H-fluoren-9-ylmethoxy)carbonyl]-2-methylalanyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-3-{[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]amino}-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

Product 1

HCID 715707242-Methylalanyl-N-[(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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Synthesis of 2-methylalanyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-3-{[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]amino}-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide (#70). According to general procedure A, from #68 (240 mg, 0.255 mmol, 1 eq.), dichloromethane (10 mL, 0.026 M) and diethylamine (10 mL) was synthesized #70 (120 mg, 65%) as a white solid/glass mix after silica gel chromatography (Gradient: 0% to 10% methanol in dichloromethane). HPLC (Protocol A at 45° C.): m/z 762.7 [M+H+], 740.4 [M+Na+], retention time=6.903 minutes; 1H NMR (400 MHz, DMSO-d6), presumed to be a mixture of rotamers, characteristic signals: δ [8.26 (d, J=8.1 Hz) and 8.49 (d, J=8.3 Hz), total 1H], [8.03 (d, J=9.5 Hz) and 8.07 (d, J=9.5 Hz), total 1H], 7.14-7.27 (m, 5H), 3.63 and 3.67 (2 s, total 3H), 3.16, 3.18, 3.20 and 3.25 (4 s, total 6H), 2.92 and 3.01 (2 br s, total 3H), 1.20 and 1.22 (2 s, total 3H), 1.12 and 1.13 (2 s, total 3H), [1.02 (d, J=6.8 Hz) and 1.06 (d, J=6.7 Hz), total 3H], 0.74-0.80 (m, 3H).

Workup

  1. customat 45° C.
  2. additiona mixture of rotamers, characteristic signals
  3. custom[8.26 (d, J=8.1 Hz) and 8.49 (d, J=8.3 Hz), total 1H], [8.03 (d, J=9.5 Hz) and 8.07 (d, J=9.5 Hz), total 1H], 7.14-7.27 (m, 5H), 3.63 and 3.67 (2 s, total 3H), 3.16, 3.18, 3.20 and 3.25 (4 s, total 6H), 2.92 and 3.01 (2 br s, total 3H), 1.20 and 1.22 (2 s, total 3H), 1.12 and 1.13 (2 s, total 3H), [1.02 (d, J=6.8 Hz) and 1.06 (d, J=6.7 Hz), total 3H], 0.74-0.80 (m, 3H)

Sources & evidence

ORD record
ord-f8ed054c81884842a3db2cf2b3b6f32a
Source dataset
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09249186B2

Reaction notes

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