Naphthalene → HCID 178486468, compound

HRID 1014470Notes

Reaction equation

HRID 1014470 reaction equation
C1C2C(=CC=CC=2)C=CC=1.[Na].[F:12][C:13]1[CH:21]=[CH:20][CH:19]=[C:18]([NH:22][C:23]2[C:24]3[CH:53]=[CH:52][N:51](S(C4C=CC(C)=CC=4)(=O)=O)[C:25]=3[N:26]=[C:27]([NH:29][C:30]3[CH:38]=[C:37]4[C:33]([CH2:34][CH2:35][N:36]4S(C4C=CC(C)=CC=4)(=O)=O)=[CH:32][C:31]=3[O:49][CH3:50])[N:28]=2)[C:14]=1[C:15]([NH2:17])=[O:16].O>C1COCC1>[F:12][C:13]1[CH:21]=[CH:20][CH:19]=[C:18]([NH:22][C:23]2[N:28]=[C:27]([NH:29][C:30]3[CH:38]=[C:37]4[C:33]([CH2:34][CH2:35][NH:36]4)=[CH:32][C:31]=3[O:49][CH3:50])[NH:26][C:25]3=[N:51][CH:52]=[CH:53][C:24]=23)[C:14]=1[C:15]([NH2:17])=[O:16]

Participants

6

Reactant 4

HCID 931NaphthaleneHCID 962WaterHCID 5360545SodiumHCID 59442045HCID 59442045, compound

Product 1

HCID 178486468HCID 178486468, compoundYield 33%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a degassed solution of naphthalene (14 g, 109 mmol) in THF (300 mL) were added sodium cubes (2.6 g, 108 mmol). The cubes were crushed, and then stirred for 4 h. A total of 60 mL of the resulting deep green solution was added dropwise to a −78° C. solution of 2-fluoro-6-({2-({5-(methyloxy)-1-[(4-methylphenyl)sulfonyl]-2,3-dihydro-1H-indol-6-yl}amino)-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)benzamide (3.7 g, 4.99 mmol) in THF (100 mL). Water (5 mL) was then added, the resulting mixture was allowed to warm to rt, and filtered. The filtrate was concentrated onto Celite and purified by silica gel chromatography using 1-10% MeOH (containing 0.2% NH3)/CH2Cl2 to obtain 2-fluoro-6-[(2-{[5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]benzamide as a yellow solid (710 mg, 33%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.88 (t, J=8.33 Hz, 2H), 3.39 (t, J=8.15 Hz, 2H), 3.76 (s, 3H), 5.07 (br s, 1H), 6.24 (s, 1H), 6.83 (s, 1H), 6.89-7.02 (m, 2H), 7.40 (s, 1H), 7.50 (q, J=7.69 Hz, 1H), 7.64 (s, 1H), 8.03 (s, 1H), 8.10 (s, 1H), 8.47 (d, J=8.42 Hz, 1H), 10.46 (s, 1H), 11.39 (s, 1H); ESIMS (M+H)+=434.17.

Workup

  1. customThe cubes were crushed
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated onto Celite
  4. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-052ac989698b45bbae8dac0fee71e5fd
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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