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Triethylamine → (S)(-)-2-(7-chloro-6-fluoro-1H-benzimidazol-1-yl)-N-{1-[4-(1-cyano-1-methylethyl)phenyl]ethyl}acetamide

HRID 419996
ノート
印刷プレビュー

反応式

HRID 419996 の反応式
[Cl:1][C:2]1[C:7]2[N:8]([CH2:11][C:12]([OH:14])=O)[CH:9]=[N:10][C:6]=2[CH:5]=[CH:4][C:3]=1[F:15].[NH2:16][C@H:17]([C:19]1[CH:24]=[CH:23][C:22]([C:25]([CH3:29])([CH3:28])[C:26]#[N:27])=[CH:21][CH:20]=1)[CH3:18].CCN(CC)CC.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CC#N.[OH-].[Na+]>[Cl:1][C:2]1[C:7]2[N:8]([CH2:11][C:12]([NH:16][C@H:17]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([C:26]#[N:27])([CH3:28])[CH3:29])=[CH:21][CH:20]=3)[CH3:18])=[O:14])[CH:9]=[N:10][C:6]=2[CH:5]=[CH:4][C:3]=1[F:15]
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 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58298447(7-chloro-6-fluoro-1H-benzimidazol-1-yl)acetic acidHCID 58298502(S)-2-(4-(1-aminoethyl)phenyl)-2-methylpropanenitrile

生成物 1

HCID 24850475
(S)(-)-2-(7-chloro-6-fluoro-1H-benzimidazol-1-yl)-N-{1-[4-(1-cyano-1-methylethyl)phenyl]ethyl}acetamide

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒HCID 14798Sodium Hydroxide溶媒

実験手順

A mixture of (7-chloro-6-fluoro-1H-benzimidazol-1-yl)acetic acid (1.00 g, 4.39 mmol) prepared according to scheme 12, (S)(−)-2-{4-[1-aminoethyl]phenyl}-2-methylpropanenitrile (825 mg 4.39 mmol) prepared according to scheme 20 or 21 and Et3N (1.33 g, 13.2 mmol, 1.84 mL) is stirred in MeCN (50.0 mL). HATU (1.67 g, 4.39 mmol) is added, and, after 2 hours of stirring, the mixture is diluted with 1N NaOH (100 mL) and then extracted 4 times with EtOAc (4×75.0 mL). The organic phases are combined and dried over Na2SO4. The mixture is filtered and concentrated. The product is purified by a Gilson prep pump, flow rate: 30 ml/min, column: Gemini™ (5u) 21.2×50 mm, mobile phase: A=10 mM ammonium bicarbonate, B=MeCN (1.01 g, 58%). 1H NMR (400 MHz, DMSO-D6) δ ppm 1.39 (d, J=7.03 Hz, 3H) 1.66 (s, 6H) 4.92 (quint, J=7.23 Hz, 1H) 5.19 (s, 2H) 7.23 (dd, J=10.16, 8.98 Hz, 1H) 7.37 (d, J=8.20 Hz, 2 H) 7.47 (d, J=8.59 Hz, 2H) 7.63 (dd, J=8.79, 4.49 Hz, 1H) 8.21 (s, 1H) 8.81 (d, J=7.81 Hz, 1 H) MS [M+H], calcd: 399.1. found: 399.2, [α]D=−165 (c=1.02 METHANOL) HRMS (ESI+) calcd for C21H21ClFN4O 399.13824 [M+H]+ found 399.13832.

後処理

  1. customprepared
  2. customprepared
  3. extractionextracted 4 times with EtOAc (4×75.0 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationThe mixture is filtered
  6. concentrationconcentrated
  7. customThe product is purified by a Gilson prep pump, flow rate: 30 ml/min, column

出典と根拠

ORDレコード
ord-2d33465104154ffba07e09752a817303
出典データセット
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08093402B2

反応ノート

読み込み中…

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