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

HRID 603148Notes

Reaction equation

HRID 603148 reaction equation
Cl.[NH2:2][CH:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]([CH3:15])([CH3:14])[C:12]#[N:13])=[C:7]([F:16])[CH:6]=1)[CH3:4].[C:17]([C:19]1[C:24]2[N:25]([CH2:28][C:29](O)=[O:30])[CH:26]=[N:27][C:23]=2[CH:22]=[CH:21][CH:20]=1)#[N:18].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:17]([C:19]1[C:24]2[N:25]([CH2:28][C:29]([NH:2][CH:3]([C:5]3[CH:10]=[CH:9][C:8]([C:11]([C:12]#[N:13])([CH3:15])[CH3:14])=[C:7]([F:16])[CH:6]=3)[CH3:4])=[O:30])[CH:26]=[N:27][C:23]=2[CH:22]=[CH:21][CH:20]=1)#[N:18]

Participants

6

Reactant 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 666491832-[4-(1-Aminoethyl)-2-fluorophenyl]-2-methylpropanenitrile hydrochloride

Product 1

HCID 598042632-(7-Cyano-1H-benzimidazol-1-yl)-N-{1-[4-(1-cyano-1-methylethyl)-3-fluorophenyl]ethyl}acetamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

2-(7-Cyano-1H-benzimidazol-1-yl)-N-{1-[4-(1-cyano-1-methylethyl)-3-fluorophenyl]ethyl}acetamide is synthesized according to example 1 by mixing 2-[4-(1-Aminoethyl)-2-fluorophenyl]-2-methylpropanenitrile hydrochloride (260 mg, 0.94 mmol) prepared according to scheme 7, (7-cyano-1H-benzimidazol-1-yl)acetic acid (200 mg, 0.94 mmol) prepared according to scheme 3 and DMAP (228 mg, 1.89 mmol, 1.00 mL) and HATU (358 mg, 2.49 mmol) in DMF (5.0 mL). The product is purified by HPLC: 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 60% 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 (69 mg, 1.77 mmol, 19%). 1H NMR (400 MHz, METHANOL-D4) δ ppm 1.50 (d, J=7.03 Hz, 3H) 1.72-1.78 (m, 6H) 5.02 (q, J=6.97 Hz, 1H) 5.31 (d, J=17.58 Hz, 1H) 5.36 (d, J=17.58 Hz, 1H) 7.17-7.25 (m, 2H) 7.39 (dd, J=8.20, 7.62 Hz, 1H) 7.43 (t, J=8.40 Hz, 1H) 7.67 (dd, J=7.62, 0.78 Hz, 1H) 7.97 (dd, J=8.20, 0.98 Hz, 1H) 8.26 (s, 1H); MS [M+H], calcd: 390.2, found: 390.3.

Workup

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

Sources & evidence

ORD record
ord-7ab667c0fe0e4cadb2ddd87855e3aa33
Source dataset
uspto-grants-2011_03
Patent number
US07906654B2

Reaction notes

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