Water → HCID 90230740, compound

HRID 519147Notes

Reaction equation

HRID 519147 reaction equation
FC(F)(F)C(O)=O.[CH3:8][CH:9]1[C:22](=[O:23])[NH:21][N:20]=[C:19]2[N:10]1[C:11]1[CH:12]=[C:13]3[N:26]([C:27]4([CH3:31])[CH2:30][NH:29][CH2:28]4)[CH2:25][CH2:24][C:14]3=[CH:15][C:16]=1[O:17][CH2:18]2.[O:32](C(OC(C)(C)C)=O)[C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=O.O>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:36]([O:35][C:33]([N:29]1[CH2:28][C:27]([CH3:31])([N:26]2[C:13]3[C:14](=[CH:15][C:16]4[O:17][CH2:18][C:19]5[N:10]([C:11]=4[CH:12]=3)[CH:9]([CH3:8])[C:22](=[O:23])[NH:21][N:20]=5)[CH2:24][CH2:25]2)[CH2:30]1)=[O:32])([CH3:39])([CH3:38])[CH3:37]

Participants

6

Reactant 3

HCID 962WaterHCID 90495Di-tert-butyl dicarbonateHCID 90284612HCID 90284612, compound

Product 1

HCID 90230740HCID 90230740, compoundYield 50.7%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-methyl-10-(3-methyl-azetidin-3-yl)-3,5,9,10-tetrahydro-8H-6-oxa-3,4,10,11b-tetraaza-cyclopenta[b]phenanthren-2-one 2,2,2-trifluoroacetate (Example #158, 0.65 g, crude, 1.985 mmol) in DCM (15 mL) was added TEA (0.603 g, 5.96 mmol), DMAP (0.024 g, 0.199 mmol) and BOC2O (0.867 g, 3.97 mmol). The resultant mixture was stirred at ambient temperature for 3 h. Water (2×10 mL) was added and the reaction mixture was extracted with EtOAc (2×40 mL). The combined organic phase was washed with brine (20 mL) and dried over anhydrous Na2SO4. After filtration, the filtrate was dried in vacuo and the residue was purified by column chromatography on silica gel (eluting with 10%-50% EtOAc in petroleum ether) to give racemic 3-methyl-3-(1-methyl-2-oxo-1,2,3,5,8,9-hexahydro-6-oxa-3,4,10,11b-tetraaza-cyclopenta[b]phenanthren-10-yl)-azetidine-1-carboxylic acid tert-butyl ester (0.43 g, 1.006 mmol). LC/MS (Table 1, Method 25) Rt=0.823 min; MS m/z: 428 [M+1]+.

Workup

  1. extractionthe reaction mixture was extracted with EtOAc (2×40 mL)
  2. washThe combined organic phase was washed with brine (20 mL)
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationAfter filtration
  5. customthe filtrate was dried in vacuo
  6. customthe residue was purified by column chromatography on silica gel (eluting with 10%-50% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-d7583b57f4a34cf4815345dff62ce963
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

Loading…