Morpholine → HCID 21106480, compound

HRID 1783676Notes

Reaction equation

HRID 1783676 reaction equation
C(OC([N:8]([C:26]1[CH:30]=[C:29]([CH3:31])[N:28](C(OC(C)(C)C)=O)[N:27]=1)[C:9]1[C:18]2[C:13](=[CH:14][C:15]([C:19](O)=[O:20])=[CH:16][CH:17]=2)[C:12](=[O:22])[N:11]([CH:23]([CH3:25])[CH3:24])[N:10]=1)=O)(C)(C)C.[NH:39]1[CH2:44][CH2:43][O:42][CH2:41][CH2:40]1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>CN(C=O)C.C(O)(C(F)(F)F)=O.C(Cl)Cl>[CH:23]([N:11]1[N:10]=[C:9]([NH:8][C:26]2[CH:30]=[C:29]([CH3:31])[NH:28][N:27]=2)[C:18]2[C:13](=[CH:14][C:15]([C:19]([N:39]3[CH2:44][CH2:43][O:42][CH2:41][CH2:40]3)=[O:20])=[CH:16][CH:17]=2)[C:12]1=[O:22])([CH3:25])[CH3:24]

Participants

6

Reactant 3

HCID 8083MorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 21106512HCID 21106512, compound

Product 1

HCID 21106480HCID 21106480, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Conditions

Temperature
0 °C

Procedure

1-[tert-Butoxycarbonyl-(1-tert-butoxycarbonyl-5-methyl-1H-pyrazol-3-yl)-amino]-3-isopropyl-4-oxo-3,4-dihydro-phthalazine-6-carboxylic acid (13 mg, 0.025 mmol) was dissolved in DMF (2 ml). To this was added morpholine (6.4 mg, 0.075 mmol) and the reaction mixture was cooled to 0° C., 2-(1H-Benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) (15 mg, 0.03 mmol) and TEA (0.014 ml, 0.1 mmol) were added consecutively and the reaction mixture stirred at RT for 24 hours. After this time, the reaction mixture was partitioned between EtOAc (10 ml) and water (10 ml). The organic layer was separated, dried (MgSO4), filtered and concentrated under vacuum. The resulting residue (13.0 mg, 0.02 mmol) was dissolved in a 20% TFA/DCM solution (2 ml) and the reaction mixture was stirred for 48 hours. After this time, the reaction mixture was concentrated and the resulting residue was triturated with diethyl ether to give the corresponding 2-Isopropyl-4-(5-methyl-1H-pyrazol-3-ylamino)-7-(morpholine-4-carbonyl)-2H-phthalazin-1-one (Example M-2). 1H-NMR: (400 MHz, D6-DMSO) 9.40 (1H, s), 8.50 (1H, d), 8.23 (1H, s), 7.91 (1H, d), 6.36 (1H, s), 5.28-5.21 (1H, m), 4.12-3.30 (8H, obscured) 2.26 (3H, s), 1.33 (6H, d) MS (ESI+)=(M+H)+ 397.21.

Workup

  1. customAfter this time, the reaction mixture was partitioned between EtOAc (10 ml) and water (10 ml)
  2. customThe organic layer was separated
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. stirringthe reaction mixture was stirred for 48 hours
  7. concentrationAfter this time, the reaction mixture was concentrated
  8. customthe resulting residue was triturated with diethyl ether

Sources & evidence

ORD record
ord-846d033a5567476b9e3db8735ab280f3
Source dataset
uspto-grants-2009_03
Patent number
US07501410B2

Reaction notes

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