Water → tert-butyl 4-[({2-tert-butyl-4-[(1,3-oxazol-2-ylmethyl)amino]pyrimidin-5-yl}carbonyl)(2-methylpropyl)amino]-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 2192876Notes

Reaction equation

HRID 2192876 reaction equation
[C:1]([C:5]1[N:10]=[C:9](Cl)[C:8]([C:12]([N:14]([CH2:32][CH:33]([CH3:35])[CH3:34])[CH:15]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH2:18][N:17]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:16]2)=[O:13])=[CH:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl.[O:37]1[CH:41]=[CH:40][N:39]=[C:38]1[CH2:42][NH2:43].C(N(C(C)C)CC)(C)C.O>CC(O)C>[C:1]([C:5]1[N:10]=[C:9]([NH:43][CH2:42][C:38]2[O:37][CH:41]=[CH:40][N:39]=2)[C:8]([C:12]([N:14]([CH2:32][CH:33]([CH3:35])[CH3:34])[CH:15]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH2:18][N:17]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:16]2)=[O:13])=[CH:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 469120601-(1,3-Oxazol-2-yl)methanamine hydrochlorideHCID 59625497tert-Butyl 4-{[(2-tert-butyl-4-chloropyrimidin-5-yl)carbonyl](2-methylpropyl)amino}-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 59625370tert-butyl 4-[({2-tert-butyl-4-[(1,3-oxazol-2-ylmethyl)amino]pyrimidin-5-yl}carbonyl)(2-methylpropyl)amino]-3,4-dihydroisoquinoline-2(1H)-carboxylateYield 75.7%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

tert-Butyl 4-{[(2-tert-butyl-4-chloropyrimidin-5-yl)carbonyl](2-methylpropyl)amino}-3,4-dihydroisoquinoline-2(1H)-carboxylate (100 mg), 1-(1,3-oxazol-2-yl)methanamine hydrochloride (54 mg) and diisopropylethylamine (0.14 ml) were dissolved in 2-propanol (2 ml), and the mixture was stirred at 80° C. for 6 hr. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and the fraction eluted with hexane-ethyl acetate (3:1) was concentrated under reduced pressure to give the object compound (85 mg).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. washthe fraction eluted with hexane-ethyl acetate (3:1)
  6. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-b285269cecce455a8ba24e8e5b696c00
Source dataset
uspto-grants-2012_12
Patent number
US08329691B2

Reaction notes

Loading…