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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
ノート
印刷プレビュー

反応式

HRID 1772386 の反応式
[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]
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 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 回HCID 89573209N-[(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

生成物 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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-f8ed054c81884842a3db2cf2b3b6f32a
出典データセット
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09249186B2

反応ノート

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