Dimethylformamide → (R)-(4-(4-chlorophthalazin-1-yl)-3-methylpiperazin-1-yl)(4,4-difluorocyclohexyl)methanone

HRID 1689976Notes

Reaction equation

HRID 1689976 reaction equation
[F:1][C:2]1([F:11])[CH2:7][CH2:6][CH:5]([C:8]([OH:10])=O)[CH2:4][CH2:3]1.O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1.CN(C=O)C.[Cl:32][C:33]1[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[C:36]([N:43]2[CH2:48][CH2:47][NH:46][CH2:45][C@H:44]2[CH3:49])=[N:35][N:34]=1>C(OCC)(=O)C.C(N(CC)CC)C>[Cl:32][C:33]1[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[C:36]([N:43]2[CH2:48][CH2:47][N:46]([C:8]([CH:5]3[CH2:4][CH2:3][C:2]([F:1])([F:11])[CH2:7][CH2:6]3)=[O:10])[CH2:45][C@H:44]2[CH3:49])=[N:35][N:34]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 27791364,4-Difluorocyclohexanecarboxylic acidHCID 57581473(R)-1-chloro-4-(2-methylpiperazin-1-yl)phthalazine

Product 1

HCID 57581526(R)-(4-(4-chlorophthalazin-1-yl)-3-methylpiperazin-1-yl)(4,4-difluorocyclohexyl)methanone

Reagents, catalysts & solvents 2

HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

4,4-difluorocyclohexanecarboxylic acid (386 mg, 2.35 mmol) and bis(2-oxo-3-oxazolidinyl)phosphinic chloride (624 mg, 2.45 mmol), DMF (4 mL), and triethylamine (0.57 mL) were stirred at RT for 2 minutes. (R)-1-chloro-4-(2-methylpiperazin-1-yl)phthalazine (JK-2) (537 mg, 2.04 mmol) was added and the reaction stirred at rt for 24 hours. The reaction was then taken up in ethyl acetate (80 mL), washed with aqueous K2CO3 (10%), water, and then saturated sodium chloride. The organics were dried (MgSO4) and evaporated to give a brown oil. Chromatography over silica gel with a gradient of hexanes/0-70% ethyl acetate gave an off-white solid, JK-27. MS (M+H)+=409.1

Workup

  1. washwashed with aqueous K2CO3 (10%), water
  2. dry with materialThe organics were dried (MgSO4)
  3. customevaporated
  4. customto give a brown oil

Sources & evidence

ORD record
ord-1245ce1632f943169786b7a0077996c3
Source dataset
uspto-grants-2012_04
Patent number
US08153633B2

Reaction notes

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