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 1625942ノート

反応式

HRID 1625942 の反応式
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]

参加物

6

反応物 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

生成物 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]carbamate収率 90.8%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-fb02ebd28cf74446b1549b7b2a40d581
出典データセット
uspto-grants-2014_07
特許番号
US08785404B2

反応ノート

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