Sodium hydride → N-(8-(6-(benzylamino)-5-(trifluoromethyl)pyridin-3-yl)-1-(6-(2-cyanopropan-2-yl)pyridin-3-yl)-3-methyl-1H-imidazo[4,5-c]quinolin-2(3H)-ylidene)cyanamide

HRID 2174958Notes

Reaction equation

HRID 2174958 reaction equation
[H-].[Na+].[NH2:3][C:4]1[N:9]=[CH:8][C:7]([C:10]2[CH:19]=[CH:18][C:17]3[N:16]=[CH:15][C:14]4[N:20]([CH3:37])[C:21](=[N:34][C:35]#[N:36])[N:22]([C:23]5[CH:24]=[N:25][C:26]([C:29]([C:32]#[N:33])([CH3:31])[CH3:30])=[CH:27][CH:28]=5)[C:13]=4[C:12]=3[CH:11]=2)=[CH:6][C:5]=1[C:38]([F:41])([F:40])[F:39]>C1COCC1>[CH2:7]([NH:3][C:4]1[N:9]=[CH:8][C:7]([C:10]2[CH:19]=[CH:18][C:17]3[N:16]=[CH:15][C:14]4[N:20]([CH3:37])[C:21](=[N:34][C:35]#[N:36])[N:22]([C:23]5[CH:24]=[N:25][C:26]([C:29]([C:32]#[N:33])([CH3:30])[CH3:31])=[CH:27][CH:28]=5)[C:13]=4[C:12]=3[CH:11]=2)=[CH:6][C:5]=1[C:38]([F:40])([F:39])[F:41])[C:10]1[CH:19]=[CH:18][CH:17]=[CH:12][CH:11]=1

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 56947515Panulisib

Product 1

HCID 56599111N-(8-(6-(benzylamino)-5-(trifluoromethyl)pyridin-3-yl)-1-(6-(2-cyanopropan-2-yl)pyridin-3-yl)-3-methyl-1H-imidazo[4,5-c]quinolin-2(3H)-ylidene)cyanamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (0.521 mmol) was added to a solution of N-(8-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-1-(6-(2-cyanopropan-2-yl)pyridin-3-yl)-3-methyl-1H-imidazo[4,5-c]quinolin-2(3H)-ylidene)cyanamide (Example 5, 0.474 mmol) in dry THF. The reaction mixture was stirred for 20 minutes, followed by the addition of dibenzylchloro phosphate (0.474 mmol). The reaction mixture was further stirred at RT for 24 h. The crude product was filtered and purified (silica gel column, MeOH/CHCl3 as eluent) to obtain the title compound. 1H NMR (300 MHz, DMSO-d6): δ 9.22 (s, 1H), 9.06 (d, J=2.4 Hz, 1H), 8.41 (dd, J=8.4, 2.4 Hz, 1H), 8.16 (d, J=9.0 Hz, 1H), 8.08 (bs, 1H), 8.01-7.97 (m, 2H), 7.81 (bs, 1H), 7.46 (m, 1H), 7.34-7.21 (m, 5H), 6.86 (d, J=1.8 Hz, 1H), 4.67 (d, 2H), 3.91 (s, 3H), 1.74 (s, 3H), 1.73 (s, 3H); MS (m/z): 618.3 (M+1)+.

Workup

  1. stirringThe reaction mixture was further stirred at RT for 24 h
  2. filtrationThe crude product was filtered
  3. custompurified (silica gel column, MeOH/CHCl3 as eluent)

Sources & evidence

ORD record
ord-5955bed43a3c459d88b327b5181271f4
Source dataset
uspto-grants-2015_06
Patent number
US09062046B2

Reaction notes

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