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 419979Notes

Reaction equation

HRID 419979 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])=[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]

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 666490292-[4-(1-Aminoethyl)phenyl]-2-methylpropanenitrile hydrochloride

Product 1

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

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-ab90df0274fc48f69597d0e67e3529d6
Source dataset
uspto-grants-2012_01
Patent number
US08093402B2

Reaction notes

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