Hydrochloric Acid → tert-butyl 5-(ethylamino)-4-[({5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]-5-oxopentanoate

HRID 1402595Notes

Reaction equation

HRID 1402595 reaction equation
[C:1]([O:5][C:6](=[O:46])[CH2:7][CH2:8][CH:9]([NH:13][C:14]([C:16]1[CH:20]=[C:19]([C:21]2[CH:26]=[C:25]([O:27][C:28]3[CH:33]=[C:32]([C:34]([NH:36][C:37]4[CH:42]=[C:41]([CH3:43])[CH:40]=[CH:39][C:38]=4[F:44])=[O:35])[CH:31]=[CH:30][C:29]=3[F:45])[CH:24]=[CH:23][N:22]=2)[NH:18][CH:17]=1)=[O:15])[C:10](O)=[O:11])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.[CH2:80]([NH2:82])[CH3:81].Cl>O1CCCC1.O>[CH2:80]([NH:82][C:10](=[O:11])[CH:9]([NH:13][C:14]([C:16]1[CH:20]=[C:19]([C:21]2[CH:26]=[C:25]([O:27][C:28]3[CH:33]=[C:32]([C:34]([NH:36][C:37]4[CH:42]=[C:41]([CH3:43])[CH:40]=[CH:39][C:38]=4[F:44])=[O:35])[CH:31]=[CH:30][C:29]=3[F:45])[CH:24]=[CH:23][N:22]=2)[NH:18][CH:17]=1)=[O:15])[CH2:8][CH2:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:46])[CH3:81]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6341EthylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 712936755-tert-butoxy-2-[({5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]-5-oxopentanoic acid

Product 1

HCID 71293530tert-butyl 5-(ethylamino)-4-[({5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]-5-oxopentanoate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

To a stirred suspension of 5-tert-butoxy-2-[({5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]-5-oxopentanoic acid (150 mg, 0.24 mmol) in 10 ml of anhydrous tetrahydrofuran were added HATU (109 mg, 0.29 mmol) and N,N-diisopropylethylamine (93 mg, 0.72 mmol). The mixture was heated at 60° C. for 15 minutes and cooled to room temperature, followed by addition of 2M ethylamine solution in THF (0.18 ml, 0.36 mmol). The mixture was stirred for another 5 minutes and poured into 100 ml of water with vigorous stirring. 1M HCl was added dropwise until pH=4. The precipitates were filtered, washed with water and dried in vacuo to give the crude, which was purified by silica gel chromatography eluting with 3˜5% methanol in chloroform to give tert-butyl 5-(ethylamino)-4-[({5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]-5-oxopentanoate as white solid. Yield: 100 mg, 64%.

Workup

  1. temperaturecooled to room temperature
  2. filtrationThe precipitates were filtered
  3. washwashed with water
  4. customdried in vacuo
  5. customto give the crude, which
  6. customwas purified by silica gel chromatography
  7. washeluting with 3˜5% methanol in chloroform

Sources & evidence

ORD record
ord-72dbb351cf8d4c899c3f9e2ea01da1a4
Source dataset
uspto-grants-2014_12
Patent number
US08906944B2

Reaction notes

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