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Diisopropylethylamine → {(1R,3S,5R)-2-[2-(3-Acetyl-indol-1-yl)-acetyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-carbamic acid 3-chloro-2-fluoro-phenyl ester

HRID 1527589
ノート
印刷プレビュー

反応式

HRID 1527589 の反応式
[Cl:1][C:2]1[C:3]([F:19])=[C:4]([O:8][C:9](=[O:18])[NH:10][CH2:11][C@@H:12]2[CH2:17][C@@H:16]3[C@@H:14]([CH2:15]3)[NH:13]2)[CH:5]=[CH:6][CH:7]=1.ClC1C(F)=C(OC(=O)NC[C@@H]2C[C@@H]3[C@@H](C3)N2C(=O)NC2C3C(=CC=CC=3)N(C(=O)N)C=2)C=CC=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[C:87]([C:90]1[C:98]2[C:93](=[CH:94][CH:95]=[CH:96][CH:97]=2)[N:92]([CH2:99][C:100](O)=[O:101])[CH:91]=1)(=[O:89])[CH3:88]>C1COCC1>[Cl:1][C:2]1[C:3]([F:19])=[C:4]([O:8][C:9](=[O:18])[NH:10][CH2:11][C@@H:12]2[CH2:17][C@@H:16]3[C@@H:14]([CH2:15]3)[N:13]2[C:100](=[O:101])[CH2:99][N:92]2[C:93]3[C:98](=[CH:97][CH:96]=[CH:95][CH:94]=3)[C:90]([C:87](=[O:89])[CH3:88])=[CH:91]2)[CH:5]=[CH:6][CH:7]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 5

HCID 81531DiisopropylethylamineHCID 1088616(3-Acetyl-indol-1-yl)-acetic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68283648[(1R,3S,5R)-2-(1-Carbamoyl-1H-indol-3-ylcarbamoyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-carbamic acid 3-chloro-2-fluoro-phenyl esterHCID 68283842
[(1R,3S,5R)-1-(2-aza-bicyclo[3.1.0]hex-3-yl)methyl]-carbamic acid 3-chloro-2-fluoro-phenyl ester

生成物 1

HCID 68283594{(1R,3S,5R)-2-[2-(3-Acetyl-indol-1-yl)-acetyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-carbamic acid 3-chloro-2-fluoro-phenyl ester

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of [(1R,3S,5R)-1-(2-aza-bicyclo[3.1.0]hex-3-yl)methyl]-carbamic acid 3-chloro-2-fluoro-phenyl ester, trifluoroacetate (prepared as described in Example 115) (60.0 mg, 0.211 mmol) in THF (3 mL) was added HBTU (120 mg, 0.316 mmol), DIPEA (0.147 mL, 0.843 mmol) and (3-acetyl-indol-1-yl)-acetic acid (50 mg, 0.232 mmol). The reaction mixture was stirred at RT for 60 h. Volatiles were removed under reduced pressure and the residue was purified by preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 30×100 mm, eluent: 20-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA, flow: 40 mL/min) to give after lyophilization of the purified HPLC fractions the title compound. MS (LC/MS): 484.0 [M+H]+; tR (HPLC conditions k): 3.69 min.

後処理

  1. customVolatiles were removed under reduced pressure
  2. customthe residue was purified by preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 30×100 mm, eluent: 20-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA, flow: 40 mL/min)

出典と根拠

ORDレコード
ord-ec3b2d406c1e449fabb8af88c572e3d0
出典データセット
uspto-grants-2015_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09085555B2

反応ノート

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