N-(tert-butoxycarbonyl)glycine → tert-butyl[2-(2-{(3E)-4-[3-methyl-4-({5-(propan-2-yl)-3-[(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)oxy]-1H-pyrazol-4-yl}methyl)phenyl]but-3-en-1-yl}-2,9-diazaspiro[5.5]undec-9-yl)-2-oxoethyl]carbamate

HRID 1625942노트

반응식

HRID 1625942 반응식
F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.Cl.Cl.[C:27]([O:30][C@@H:31]1[C@@H:68]([O:69][C:70](=[O:72])[CH3:71])[C@H:67]([O:73][C:74](=[O:76])[CH3:75])[C@@H:66]([CH2:77][O:78][C:79](=[O:81])[CH3:80])[O:65][C@H:32]1[O:33][C:34]1[C:38]([CH2:39][C:40]2[CH:45]=[CH:44][C:43](/[CH:46]=[CH:47]/[CH2:48][CH2:49][N:50]3[CH2:55][CH2:54][CH2:53][C:52]4([CH2:60][CH2:59][NH:58][CH2:57][CH2:56]4)[CH2:51]3)=[CH:42][C:41]=2[CH3:61])=[C:37]([CH:62]([CH3:64])[CH3:63])[NH:36][N:35]=1)(=[O:29])[CH3:28].[CH3:82][C:83]([O:86][C:87]([NH:89][CH2:90][C:91](O)=[O:92])=[O:88])([CH3:85])[CH3:84].C(N(C(C)C)CC)(C)C>ClCCl>[C:83]([O:86][C:87](=[O:88])[NH:89][CH2:90][C:91]([N:58]1[CH2:57][CH2:56][C:52]2([CH2:51][N:50]([CH2:49][CH2:48]/[CH:47]=[CH:46]/[C:43]3[CH:44]=[CH:45][C:40]([CH2:39][C:38]4[C:34]([O:33][C@@H:32]5[O:65][C@H:66]([CH2:77][O:78][C:79](=[O:81])[CH3:80])[C@@H:67]([O:73][C:74](=[O:76])[CH3:75])[C@H:68]([O:69][C:70](=[O:72])[CH3:71])[C@H:31]5[O:30][C:27](=[O:29])[CH3:28])=[N:35][NH:36][C:37]=4[CH:62]([CH3:64])[CH3:63])=[C:41]([CH3:61])[CH:42]=3)[CH2:55][CH2:54][CH2:53]2)[CH2:60][CH2:59]1)=[O:92])([CH3:85])([CH3:82])[CH3:84]

참가 물질

6

반응물 4

HCID 78288N-(tert-butoxycarbonyl)glycineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 867208844-{4-[(1E)-4-(2,9-diazaspiro[5.5]undec-2-yl)but-1-en-1-yl]-2-methylbenzyl}-5-(propan-2-yl)-1H-pyrazol-3-yl 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranoside dihydrochloride

생성물 1

HCID 131731669tert-butyl[2-(2-{(3E)-4-[3-methyl-4-({5-(propan-2-yl)-3-[(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)oxy]-1H-pyrazol-4-yl}methyl)phenyl]but-3-en-1-yl}-2,9-diazaspiro[5.5]undec-9-yl)-2-oxoethyl]carbamate수율 90.8%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

Add O-(7-azabenzotriazol-1-yl)-N,N,N′,N′ tetramethyluronium hexafluorophosphate (HATU, 543 mg, 1.43 mmol) to a solution of 4-{4-[(1E)-4-(2,9-diazaspiro[5.5]undec-2-yl)but-1-en-1-yl]-2-methylbenzyl}-5-(propan-2-yl)-1H-pyrazol-3-yl 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranoside dihydrochloride (1.0 g, 1.19 mmol), N-alpha-T-Boc-glycine (317 mg, 1.79 mmol), and diisopropylethylamine (769 mg, 5.95 mmol) in dichloromethane (10 mL). Stir the mixture at room temperature for 2.0 hours. Remove the solvent under the reduced pressure. Purify the resulting residue by flash chromatography (silica gel, gradient ethyl acetate/dichloromethane from 30-85% over 20 min, 40 g column) to provide the title compound (1.0 g, 1.08 mmol). MS (m/z): 924.4 (M+1), 922.4 (M−1).

후처리

  1. customRemove the solvent under the reduced pressure
  2. customPurify the resulting residue by flash chromatography (silica gel, gradient ethyl acetate/dichloromethane from 30-85% over 20 min, 40 g column)

출처 및 근거

ORD 기록
ord-fb02ebd28cf74446b1549b7b2a40d581
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08785404B2

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