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 603145노트

반응식

HRID 603145 반응식
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]

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 11195002(7-Cyano-1H-benzimidazol-1-yl)acetic acidHCID 666490292-[4-(1-Aminoethyl)phenyl]-2-methylpropanenitrile hydrochloride

생성물 1

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

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6228Dimethylformamide용매

실험 절차

2-[4-(1-Aminoethyl)phenyl]-2-methylpropanenitrile hydrochloride prepared according to scheme 6 (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.

후처리

  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

출처 및 근거

ORD 기록
ord-a51a5e127c814083a5b19eb2628f3690
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07906654B2

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