Triethylamine → HCID 68108835, compound

HRID 538298Notes

Reaction equation

HRID 538298 reaction equation
BrC1C=CC([C:8]([OH:10])=[O:9])=NC=1.Cl[C:12](N(C)C)=[C:13]([CH3:15])[CH3:14].[NH2:19][C:20]1[CH2:25][O:24][CH2:23][C@:22]([C:27]2[N:32]=[C:31]([NH:33][C:34]([C:36]3[CH:41]=[CH:40][C:39]([Br:42])=[CH:38][N:37]=3)=[O:35])[CH:30]=[CH:29][CH:28]=2)([CH3:26])[N:21]=1.CCN(CC)CC>C(Cl)Cl>[C:13]([O:10][C:8](=[O:9])[NH:19][C:20]1[CH2:25][O:24][CH2:23][C@:22]([C:27]2[CH:28]=[CH:29][CH:30]=[C:31]([NH:33][C:34]([C:36]3[CH:41]=[CH:40][C:39]([Br:42])=[CH:38][N:37]=3)=[O:35])[N:32]=2)([CH3:26])[N:21]=1)([CH3:15])([CH3:14])[CH3:12]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 6085445-Bromopyridine-2-carboxylic acidHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 70356238HCID 70356238, compound

Product 1

HCID 68108835HCID 68108835, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of 5-bromopyridine-2-carboxylic acid (34.5 mg, 0.171 mmol) in DCM (2 ml) was added 1-chloro-N,N,2-trimethylpropenylamine (0.045 ml, 45.7 mg, 0.342 mmol) and the reaction mixture was stirred at 0° C. for 1 h. The reaction mixture was then added dropwise to a dry solution of (−)-5-(6-amino-pyridin-2-yl)-5-methyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester (enantiomer 1 from procedure step j) above, 47.6 mg, 0.155 mmol) and NEt3 (0.048 ml, 34.6 mg, 0.342 mmol) in DCM (2 ml) at 0° C. The reaction mixture was allowed to warm to rt and to stir for 20 min at rt. The reaction mixture was diluted with DCM and quenched with H2O. The phases were separated and the aq. phase was extracted with DCM. The combined org. phases were washed with brine, dried over Na2SO4, filtered and twice purified by HPLC (Alltech Grom Saphir65 Si 10 μM column 150×30 mm, gradient 1 n-heptane:EtOAc 0-1.2 min 85:15, 1.2-9 min 0:100, 9-12 min 0:100, gradient 2 n-heptane:EtOAc:MeOH 0-1.2 min 47:50:3, 1.2-9 min 0:60:40, 9-12 min 0:60:40, flow 50 ml/min, detection 254 nm]. HPLC RtH4=1.10 min; ESIMS: 490, 492 [(M+H)+].

Workup

  1. temperatureto warm to rt
  2. stirringto stir for 20 min at rt
  3. customquenched with H2O
  4. customThe phases were separated
  5. extractionthe aq. phase was extracted with DCM
  6. washphases were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customtwice purified by HPLC (Alltech Grom Saphir65 Si 10 μM column 150×30 mm, gradient 1 n-heptane
  10. customEtOAc 0-1.2 min 85:15, 1.2-9 min 0:100, 9-12 min 0:100, gradient 2 n-heptane
  11. customMeOH 0-1.2 min 47:50:3, 1.2-9 min 0:60:40, 9-12 min 0:60:40
  12. customHPLC RtH4=1.10 min

Sources & evidence

ORD record
ord-93f7ead372e243ab9481965b28ef23f8
Source dataset
uspto-grants-2014_10
Patent number
US08865712B2

Reaction notes

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