Diisopropylethylamine → HCID 53468859, compound

HRID 1910062Notes

Reaction equation

HRID 1910062 reaction equation
Cl.Cl.[NH:3]1[C:11]2[C:6](=[CH:7][C:8]([C:12]3[C:20]4[C:19]([NH2:21])=[N:18][CH:17]=[N:16][C:15]=4[N:14]([CH3:22])[CH:13]=3)=[CH:9][CH:10]=2)[CH2:5][CH2:4]1.[F:23][C:24]1[CH:29]=[CH:28][C:27]([CH2:30][C:31](O)=[O:32])=[CH:26][C:25]=1[C:34]([F:37])([F:36])[F:35].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>O>[F:23][C:24]1[CH:29]=[CH:28][C:27]([CH2:30][C:31]([N:3]2[C:11]3[C:6](=[CH:7][C:8]([C:12]4[C:20]5[C:19]([NH2:21])=[N:18][CH:17]=[N:16][C:15]=5[N:14]([CH3:22])[CH:13]=4)=[CH:9][CH:10]=3)[CH2:5][CH2:4]2)=[O:32])=[CH:26][C:25]=1[C:34]([F:35])([F:36])[F:37]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27375934-Fluoro-3-(trifluoromethyl)phenylacetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 668234705-(2,3-dihydro-1H-indol-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine dihydrochloride

Product 1

HCID 53468859HCID 53468859, compoundYield 95.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of 5-(2,3-dihydro-1H-indol-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine 2HCl (150 mg, 0.443 mmol), [4-fluoro-3-(trifluoromethyl)phenyl]acetic acid (99 mg, 0.443 mmol), HATU (169 mg, 0.443 mmol), and DIEA (0.310 mL, 1.774 mmol) was stirred at room temperature overnight. LCMS analysis indicated good conversion, so the resulting suspension was poured into water (10 mL) and stirred for 30 min, forming a precipitate. This precipitate was collected by filtration, dried at the pump for an hour, then adsorbed onto silica and purified by flash chromatography (0-8% MeOH in EtOAc, 12-g column) to afford 5-(1-{[4-fluoro-3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (198 mg, 95% yield) as a white solid. LC-MS (ES) m/z=470 [M+H]+. 1H NMR (400 MHz, DMSO-d6) ppm 3.26 (t, J=8.46 Hz, 2H), 3.74 (s, 3H), 4.02 (s, 2H), 4.27 (t, J=8.34 Hz, 2H), 5.91-6.20 (m, 2H), 7.19-7.29 (m, 2H), 7.33 (s, 1H), 7.50 (t, J=9.73 Hz, 1H), 7.64-7.70 (m, 1H), 7.73 (d, J=6.57 Hz, 1H), 8.11 (d, J=8.34 Hz, 1H), 8.15 (s, 1H).

Workup

  1. customforming a precipitate
  2. filtrationThis precipitate was collected by filtration
  3. customdried at the pump for an hour
  4. custompurified by flash chromatography (0-8% MeOH in EtOAc, 12-g column)

Sources & evidence

ORD record
ord-6089cd165fac48c6b1677d33c35ae9d6
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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