Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → N-{1-[4-(1-Cyano-1-methylethyl)phenyl]ethyl}-2-(6,7-difluoro-1H-benzimidazol-1-yl)acetamide

HRID 419980노트

반응식

HRID 419980 반응식
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[CH:8][N:7]([CH2:10][C:11]([OH:13])=O)[C:6]=2[C:14]=1[F:15].Cl.[NH2:17][CH:18]([C:20]1[CH:25]=[CH:24][C:23]([C:26]([CH3:30])([CH3:29])[C:27]#[N:28])=[CH:22][CH:21]=1)[CH3:19].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:27]([C:26]([C:23]1[CH:22]=[CH:21][C:20]([CH:18]([NH:17][C:11](=[O:13])[CH2:10][N:7]2[C:6]3[C:14]([F:15])=[C:2]([F:1])[CH:3]=[CH:4][C:5]=3[N:9]=[CH:8]2)[CH3:19])=[CH:25][CH:24]=1)([CH3:30])[CH3:29])#[N:28]

참가 물질

6

반응물 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57939018HCID 57939018, 화합물HCID 666490292-[4-(1-Aminoethyl)phenyl]-2-methylpropanenitrile hydrochloride

생성물 1

HCID 24850276N-{1-[4-(1-Cyano-1-methylethyl)phenyl]ethyl}-2-(6,7-difluoro-1H-benzimidazol-1-yl)acetamide

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6228Dimethylformamide용매

실험 절차

N-{1-[4-(1-Cyano-1-methylethyl)phenyl]ethyl}-2-(6,7-difluoro-1H-benzimidazol-1-yl)acetamide is synthesized according to example 1 by mixing (6,7-difluoro-1H-benzimidazol-1-yl)acetic acid (500 mg, 2.36 mmol) prepared according to scheme 2, 2-[4-(1-aminoethyl)phenyl]-2-methylpropanenitrile hydrochloride (525 mg, 2.36 mmol) prepared according to scheme 6, DMAP (570 mg, 4.71 mmol) and HATU (896 mg, 2.36 mmol) in DMF (10.0 mL). The product is purified on HPLCMS: Waters prep LCMS, 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 60% B in A, in 10 min. The fractions are combined, NaOH 1 N is added and the desired compound is extracted with ethyl acetate. The combined organic fractions are concentrated under reduced pressure to yield the product (450 mg, 2.36 mmol, 50%). 1H NMR (400 MHz, METHANOL-D4) δ ppm 1.49 (d, J=7.03 Hz, 3H) 1.68 (s, 6H) 5.03 (m, 1H) 5.20 (m, 2H) 7.30 (dt, J=11.23, 8.98, 7.32 Hz, 1H) 7.35-7.42 (m, 2H) 7.44-7.54 (m, 3H) 8.56 (s, 1H) MS [M+H], calcd: 383.2. found: 383.3.

후처리

  1. customprepared
  2. customprepared
  3. customThe product is purified on HPLCMS
  4. additionNaOH 1 N is added
  5. extractionthe desired compound is extracted with ethyl acetate
  6. concentrationThe combined organic fractions are concentrated under reduced pressure

출처 및 근거

ORD 기록
ord-d7b210fb896348dd86011e2bf174315e
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08093402B2

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