Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → (S)(-)-2-(7-Cyano-1H-benzimidazol-1-yl)-N-{1-[4-(1-cyano-1-methylethyl)phenyl]ethyl}acetamide

HRID 419979ノート

反応式

HRID 419979 の反応式
Cl.[NH2:2][CH:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]([CH3:15])([CH3:14])[C:12]#[N:13])=[CH:7][CH:6]=1)[CH3:4].[C:16]([C:18]1[C:23]2[N:24]([CH2:27][C:28](O)=[O:29])[CH:25]=[N:26][C:22]=2[CH:21]=[CH:20][CH:19]=1)#[N:17].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C1C=CN=CC=1)C.CN(C=O)C>[C:16]([C:18]1[C:23]2[N:24]([CH2:27][C:28]([NH:2][C@H:3]([C:5]3[CH:10]=[CH:9][C:8]([C:11]([C:12]#[N:13])([CH3:14])[CH3:15])=[CH:7][CH:6]=3)[CH3:4])=[O:29])[CH:25]=[N:26][C:22]=2[CH:21]=[CH:20][CH:19]=1)#[N:17]

参加物

6

反応物 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11195002(7-Cyano-1H-benzimidazol-1-yl)acetic acidHCID 666490292-[4-(1-Aminoethyl)phenyl]-2-methylpropanenitrile hydrochloride

生成物 1

HCID 24178472(S)(-)-2-(7-Cyano-1H-benzimidazol-1-yl)-N-{1-[4-(1-cyano-1-methylethyl)phenyl]ethyl}acetamide収率 66%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6228Dimethylformamide溶媒

実験手順

2-[4-(1-Aminoethyl)phenyl]-2-methylpropanenitrile hydrochloride prepared according to scheme (557 mg, 2.49 mmol), (7-cyano-1H-benzimidazol-1-yl)acetic acid (500 mg, 2.49 mmol) prepared according to scheme 3 and DMAP (601 mg, 4.97 mmol) are mixed in DMF (10.0 mL). HATU (945 mg, 2.49 mmol) is added, and the mixture is stirred for 18 hours. The reaction mixture is filtered and then purified on HPLCMS: Waters prep LCMS, Flow rate: 27 ml/min, Column: SynerSi (4μ) Polar RP, 21.2×50 mm, Mobile phase: A=water (0.05% TFA) B=MeCN, Gradient used 40% to 70% B in A, in 10 min. The fractions are combined, NaOH 1N is added and the desired compound is extracted with ethyl acetate. The combined organic fractions are concentrated under reduced pressure to yield the product (610 mg, 1.64 mmol, 66%). 1H NMR (400 MHz, METHANOL-D4) δ ppm 1.50 (d, J=7.03 Hz, 3H) 1.68 (s, 6H) 4.98-5.09 (m, 1H) 5.33 (s, 2H) 7.37-7.43 (m, 3H) 7.46 (d, J=8.20 Hz, 2H) 7.68 (d, J=7.62 Hz, 1H) 7.97 (dd, J=8.20, 0.98 Hz, 1H) 8.28 (s, 1H) 8.89 (d, J=7.62 Hz, 1H), MS [M+H], calcd: 372.2. found: 372.3.

後処理

  1. customprepared
  2. filtrationThe reaction mixture is filtered
  3. custompurified on HPLCMS
  4. waitin 10 min
  5. additionNaOH 1N is added
  6. extractionthe desired compound is extracted with ethyl acetate
  7. concentrationThe combined organic fractions are concentrated under reduced pressure

出典と根拠

ORDレコード
ord-ab90df0274fc48f69597d0e67e3529d6
出典データセット
uspto-grants-2012_01
特許番号
US08093402B2

反応ノート

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