Trifluoroacetic acid → HCID 86679641, compound

HRID 577696Notes

Reaction equation

HRID 577696 reaction equation
C(OC([N:8]1[CH2:12][C@H:11]([O:13][CH3:14])[C@@H:10]([CH2:15][O:16][C:17]2[C:18]3[C:32]([Cl:33])=[CH:31][NH:30][C:19]=3[N:20]=[C:21]([NH:23][C:24]3[CH:25]=[N:26][N:27]([CH3:29])[CH:28]=3)[N:22]=2)[CH2:9]1)=O)(C)(C)C.[C:34]([OH:40])([C:36]([F:39])([F:38])[F:37])=[O:35]>C(Cl)Cl>[F:37][C:36]([F:39])([F:38])[C:34]([OH:40])=[O:35].[Cl:33][C:32]1[C:18]2[C:17]([O:16][CH2:15][C@@H:10]3[C@@H:11]([O:13][CH3:14])[CH2:12][NH:8][CH2:9]3)=[N:22][C:21]([NH:23][C:24]3[CH:25]=[N:26][N:27]([CH3:29])[CH:28]=3)=[N:20][C:19]=2[NH:30][CH:31]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 866796431-Pyrrolidinecarboxylic acid, 3-[[[5-chloro-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]methyl]-4-methoxy-, 1,1-dimethylethyl ester, (3R,4R)-

Product 1

HCID 86679641HCID 86679641, compoundYield 122.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (3R,4R)-3-[5-chloro-2-(1-methyl-1H-pyrazol-4-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxymethyl]-4-methoxy-pyrrolidine-1-carboxylic acid tert-butyl ester (12.40 g, 26 mmol) in DCM (60 mL) at 0° C. was added TFA (10.1 mL, 208 mmol) and the resulting solution was stirred at ambient temperature for 2.5 hrs. The volatiles were removed and to the residue was added ethyl ether (150 mL). The resulting suspension was stirred for 2 hrs then filtered to afford a light pink solid. This was washed with ethyl ether (30 mL) and dried to give the title compound (15.69 g, quant) as a TFA salt. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.56 (br. s., 1H) 9.09 (s, 3H) 7.85 (s, 1H) 7.54 (s, 1H) 7.09 (d, J=2.32 Hz, 1H) 4.48 (d, J=6.48 Hz, 2H) 4.11 (br. s., 1H) 3.81 (s, 3H) 3.46-3.60 (m, 1H) 3.35-3.45 (m, 2H) 3.32 (s, 3H) 3.15 (dq, J=12.01, 6.02 Hz, 1H) 2.88 (m, J=6.42, 6.42 Hz, 1H). m/z (APCI+) for parent molecule C16H20ClN7O2 378.2 (M+H)+ with Cl isotope pattern.

Workup

  1. customThe volatiles were removed and to the residue
  2. additionwas added ethyl ether (150 mL)
  3. stirringThe resulting suspension was stirred for 2 hrs
  4. filtrationthen filtered
  5. customto afford a light pink solid
  6. washThis was washed with ethyl ether (30 mL)
  7. customdried

Sources & evidence

ORD record
ord-a6d7023f2ccb47999b49afe5ccb5ee53
Source dataset
uspto-grants-2015_05
Patent number
US09040547B2

Reaction notes

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