Hydrochloric Acid → N-((S)-((S)-5,5-dimethylpyrrolidin-2-yl)(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-(tetrahydro-2H-pyran-4-ylamino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxamide

HRID 2279552Notes

Reaction equation

HRID 2279552 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[C@H:12]([NH:27][C:28]([N:30]1[CH2:39][CH2:38][C:37]2[CH:36]=[N:35][C:34]([NH:40][CH:41]3[CH2:46][CH2:45][O:44][CH2:43][CH2:42]3)=[N:33][C:32]=2[CH2:31]1)=[O:29])[C@H:13]1[N:17](C(OC(C)(C)C)=O)[C:16]([CH3:26])([CH3:25])[CH2:15][CH2:14]1.Cl.CC(O)C.C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl>[CH3:25][C:16]1([CH3:26])[NH:17][C@H:13]([C@H:12]([C:3]2[CH:4]=[CH:5][C:6]([C:8]([F:10])([F:9])[F:11])=[CH:7][C:2]=2[F:1])[NH:27][C:28]([N:30]2[CH2:39][CH2:38][C:37]3[CH:36]=[N:35][C:34]([NH:40][CH:41]4[CH2:42][CH2:43][O:44][CH2:45][CH2:46]4)=[N:33][C:32]=3[CH2:31]2)=[O:29])[CH2:14][CH2:15]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3776IsopropanolHCID 10340Sodium CarbonateHCID 86705539(S)-tert-butyl 5-((S)-(2-fluoro-4-(trifluoromethyl)phenyl)(2-(tetrahydro-2H-pyran-4-ylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine-7-carboxamido)methyl)-2,2-dimethylpyrrolidine-1-carboxylate

Product 1

HCID 86705540N-((S)-((S)-5,5-dimethylpyrrolidin-2-yl)(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-(tetrahydro-2H-pyran-4-ylamino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 324 (0.380 g, 0.584 mmol) and DCM (5 mL). was added 6M HCl in IPA (0.973 mL, 5.84 mmol) and the reaction was stirred for 1 h and then poured into Na2CO3 and extracted with DCM. The combined organic extracts were dried (MgSO4), filtered, and concentrated in vacuo. The crude product was purified by SiO2 chromatography eluting with a DCM/MeOH gradient (500:40 to 500:50) to afford 0.210 g (65.3%) of I-86: MS m/z (APCI-pos) M+1=551.

Workup

  1. extractionextracted with DCM
  2. dry with materialThe combined organic extracts were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by SiO2 chromatography
  6. washeluting with a DCM/MeOH gradient (500:40 to 500:50)
  7. customto afford 0.210 g (65.3%) of I-86

Sources & evidence

ORD record
ord-502fa53609a34ee5bd225cdc3ebe6b47
Source dataset
uspto-grants-2015_09
Patent number
US09133187B2

Reaction notes

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