Hydrochloric Acid → HCID 86290884, compound

HRID 525817Notes

Reaction equation

HRID 525817 reaction equation
[C:1]([O:5][C:6](=[O:45])[CH2:7][CH2:8][C@H:9]([NH:13][C:14]([C:16]1[S:24][C:23]2[C:18](=[N:19][CH:20]=[CH:21][C:22]=2[O:25][C:26]2[CH:31]=[CH:30][C:29]([NH:32][C:33]([NH:35][C:36]3[CH:41]=[C:40]([CH3:42])[CH:39]=[CH:38][C:37]=3[F:43])=[O:34])=[C:28]([F:44])[CH:27]=2)[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.[CH2:79]([NH2:81])[CH3:80].Cl>O1CCCC1.O>[CH2:79]([NH:81][C:10](=[O:11])[C@@H:9]([NH:13][C:14]([C:16]1[S:24][C:23]2[C:18](=[N:19][CH:20]=[CH:21][C:22]=2[O:25][C:26]2[CH:31]=[CH:30][C:29]([NH:32][C:33]([NH:35][C:36]3[CH:41]=[C:40]([CH3:42])[CH:39]=[CH:38][C:37]=3[F:43])=[O:34])=[C:28]([F:44])[CH:27]=2)[CH:17]=1)=[O:15])[CH2:8][CH2:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:45])[CH3:80]

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 86290885HCID 86290885, compound

Product 1

HCID 86290884HCID 86290884, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

To a stirred suspension of (2S)-5-tert-butoxy-2-[({7-[3-fluoro-4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]thieno[3,2-b]pyridin-2-yl}carbonyl)amino]-5-oxopentanoic acid (100 mg, 0.16 mmol) in 10 ml of anhydrous tetrahydrofuran were added HATU (73 mg, 0.19 mmol) and N,N-diisopropylethylamine (62 mg, 0.48 mmol). The mixture was heated at 60° C. for 10 minutes, followed by addition of 2M ethylamine solution in THF (0.25 ml, 0.50 mmol). The mixture was heated at 60° C. for another 5 minutes, cooled to room temperature 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 (4S)-5-(ethylamino)-4-[({7-[3-fluoro-4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]thieno[3,2-b]pyridin-2-yl}carbonyl)amino]-5-oxopentanoate as white solid. Yield: 73 mg, 70%.

Workup

  1. temperatureThe mixture was heated at 60° C. for another 5 minutes
  2. temperaturecooled to room temperature
  3. filtrationThe precipitates were filtered
  4. washwashed with water
  5. customdried in vacuo
  6. customto give the crude, which
  7. customwas purified by silica gel chromatography
  8. washeluting with 3˜5% methanol in chloroform

Sources & evidence

ORD record
ord-2aac16be2d254832b51f6d37bb7dc52c
Source dataset
uspto-grants-2016_05
Patent number
US09340555B2

Reaction notes

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