Dichloromethane → HCID 86705534, compound

HRID 2279547Notes

Reaction equation

HRID 2279547 reaction equation
[NH2:1][C@@H:2]([C:13]1[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[C:15]([F:23])[CH:14]=1)[CH2:3][N:4]([CH3:12])[C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8].C(Cl)Cl.C1N=CN([C:32](N2C=NC=C2)=[O:33])C=1.[N:39]1[C:44]2[CH2:45][NH:46][CH2:47][CH2:48][C:43]=2[CH:42]=[N:41][C:40]=1[NH:49][C@@H:50]([CH3:53])[CH2:51][OH:52]>O>[F:23][C:15]1[CH:14]=[C:13]([C@H:2]([NH:1][C:32]([N:46]2[CH2:47][CH2:48][C:43]3[CH:42]=[N:41][C:40]([NH:49][C@@H:50]([CH3:53])[CH2:51][OH:52])=[N:39][C:44]=3[CH2:45]2)=[O:33])[CH2:3][N:4]([CH3:12])[C:5](=[O:11])[O:6][C:7]([CH3:8])([CH3:9])[CH3:10])[CH:18]=[CH:17][C:16]=1[C:19]([F:20])([F:21])[F:22]

Participants

6

Reactant 4

HCID 6344Dichloromethane2×HCID 682631,1'-CarbonyldiimidazoleHCID 68295199HCID 68295199, compoundHCID 86705535HCID 86705535, compound

Product 1

HCID 86705534HCID 86705534, compoundYield 26.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of (S)-tert-butyl 2-amino-2-(3-fluoro-4-(trifluoromethyl)phenyl)ethyl(methyl)carbamate (0.220 g, 0.654 mmol) and DCM (5 mL) was cooled to 0° C. was added sequentially TEA (0.365 mL, 2.62 mmol) and CDI (0.106 g, 0.654 mmol). The reaction was stirred for 30 min then added to a solution of 138 (0.160 g, 0.654 mmol), TEA (0.365 mL, 2.62 mmol) and DCM (5 mL) at RT and the resulting solution was stirred at RT for 18 h. The solution 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 a DCM/MeOH gradient (500:10 to 500:20) to afford 0.100 g (26.8%) of tert-butyl (S)-2-(3-fluoro-4-(trifluoromethyl)phenyl)-2-(2-((S)-1-hydroxypropan-2-ylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine-7-carboxamido)ethyl(methyl)carbamate (318).

Workup

  1. stirringthe resulting solution was stirred at RT for 18 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 a DCM/MeOH gradient (500:10 to 500:20)

Sources & evidence

ORD record
ord-6cc1ca2cf3f542009f9715683fcbfb95
Source dataset
uspto-grants-2015_09
Patent number
US09133187B2

Reaction notes

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