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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
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HRID 1772386 반응식
[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]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

6

반응물 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-valinamide2회HCID 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

생성물 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

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-f8ed054c81884842a3db2cf2b3b6f32a
출처 데이터셋
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09249186B2

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