Hydrochloric Acid → HCID 66967621, compound

HRID 1362253Notes

Reaction equation

HRID 1362253 reaction equation
C(#N)CC.[NH2:5][C:6]1[N:13]=[CH:12][C:11](Br)=[CH:10][C:7]=1[C:8]#[N:9].[CH3:15][N:16]([CH2:21][C:22]1[N:23]([CH3:31])[C:24]2[C:29]([CH:30]=1)=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:17](=[O:20])[CH:18]=[CH2:19].C(N(C(C)C)CC)(C)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[ClH:63]>CC([O-])=O.CC([O-])=O.[Pd+2]>[ClH:63].[NH2:5][C:6]1[N:13]=[CH:12][C:11](/[CH:19]=[CH:18]/[C:17]([N:16]([CH3:15])[CH2:21][C:22]2[N:23]([CH3:31])[C:24]3[C:29]([CH:30]=2)=[CH:28][CH:27]=[CH:26][CH:25]=3)=[O:20])=[CH:10][C:7]=1[C:8]#[N:9]

Participants

8

Reactant 6

HCID 313Hydrochloric Acid2×HCID 7854PropionitrileHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 20752825N-Methyl-N-[(1-methyl-2-indolyl)methyl]acrylamideHCID 242291992-Amino-5-bromopyridine-3-carbonitrile

Product 1

HCID 66967621HCID 66967621, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
100 °C

Procedure

A propionitrile (15 mL) solution of 2-amino-5-bromo-nicotinonitrile (198 mg, 1 mmol), N-methyl-N-(1-methyl-1H-indol-2-ylmethyl)-acrylamide (457 mg, 2 mmol) and diisopropyl-ethylamine (523 μL, 3 mmol) was purged with Argon for 10 min. Pd(OAc)2 (23 mg, 0.1 mmol) and P(o-Tol)3 (61 mg, 0.2 mmol) was added and the Argon purge was repeated. The mixture was heated to 100° C. and stirred for 6 hr under Argon. Upon cooling, solvents were removed under vacuo and the residue was purified by Flash chromatography (silica, 2% MeOH in CH2Cl2). The purified free base was converted to its HCl salt by addition of HCl (1 mL, 1 mmol, 1M in ether). The salt was washed with ether and dried to afford 162 mg (43%) of the title compound. 1H NMR (300 MHz, DMSO-d6) δ 8.50 (m, 2H), 7.55-6.95 (m, 4H), 6.40 and 6.17 (rotamers, 2s, 1H), 5.03 and 4.83 (rotamers, 2s, 2H), 3.71 and 3.67 (rotamers, 2s, 3H), 3.09 and 2.96 (rotamers, 2s, 3H). MS (ESI) m/e: 346.1662 (M+H)+.

Workup

  1. customthe Argon purge
  2. temperatureUpon cooling
  3. customsolvents were removed under vacuo
  4. customthe residue was purified by Flash chromatography (silica, 2% MeOH in CH2Cl2)
  5. washThe salt was washed with ether
  6. customdried

Sources & evidence

ORD record
ord-23eed17cdbb7458283c2011f944b965b
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

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