Dichloromethane → N-((S)-2-(tert-butyldimethylsilyloxy)-1-(3,4-dichlorophenyl)ethyl)-2-(1,1,1-trifluoropropan-2-ylamino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxamide

HRID 2279539Notes

Reaction equation

HRID 2279539 reaction equation
[Si:1]([O:8][CH2:9][C@H:10]([C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[C:14](F)[CH:13]=1)[NH2:11])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(Cl)[Cl:21].C1N=CN([C:28](N2C=NC=C2)=[O:29])C=1.[F:35][C:36]([F:51])([F:50])[CH:37]([NH:39][C:40]1[N:41]=[CH:42][C:43]2[CH2:49][CH2:48][NH:47][CH2:46][C:44]=2[N:45]=1)[CH3:38]>O>[Si:1]([O:8][CH2:9][C@@H:10]([NH:11][C:28]([N:47]1[CH2:48][CH2:49][C:43]2[CH:42]=[N:41][C:40]([NH:39][CH:37]([CH3:38])[C:36]([F:35])([F:50])[F:51])=[N:45][C:44]=2[CH2:46]1)=[O:29])[C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([Cl:21])[CH:13]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 6344Dichloromethane2×HCID 682631,1'-CarbonyldiimidazoleHCID 68294199N-(1,1,1-trifluoropropan-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-amineHCID 86705474(S)-2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethanamine

Product 1

HCID 68294705N-((S)-2-(tert-butyldimethylsilyloxy)-1-(3,4-dichlorophenyl)ethyl)-2-(1,1,1-trifluoropropan-2-ylamino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxamideYield 83.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of 85 (0.104 g, 0.325 mmol) and DCM (5 mL) at RT was added TEA (0.136 mL, 0.975 mmol) and CDI (0.0527 g, 0.325 mmol) and the reaction was stirred at RT for 30 min and then added to a solution of 300 (0.080 g, 0.325 mmol), TEA (0.136 ml, 0.975 mmol) and DCM (5 mL) solution and the resulting solution stirred for 4 h. The reaction mixture was poured into water 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 DCM/MeOH (500:7) to afford 0.160 g (83.1%) of N—((S)-2-(tert-butyldimethylsilyloxy)-1-(3,4-dichlorophenyl)ethyl)-2-(1,1,1-trifluoropropan-2-ylamino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxamide (302).

Workup

  1. stirringthe resulting solution stirred for 4 h
  2. extractionextracted with DCM
  3. dry with materialThe combined organic extracts were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by SiO2 chromatography
  7. washeluting with DCM/MeOH (500:7)

Sources & evidence

ORD record
ord-86149794adf04f6ba2bde03f2489b710
Source dataset
uspto-grants-2015_09
Patent number
US09133187B2

Reaction notes

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