Methanol → 1-[3-(6-tert-Butyl-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-3-[4-(morpholine-4-carbonyl)-phenylamino]-1H-pyrazole-4-carboxylic acid amide

HRID 1025585Notes

Reaction equation

HRID 1025585 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[C:11](=[O:15])[N:10]([C:16]1[C:17]([CH:44]=[O:45])=[C:18]([N:22]3[CH:26]=[C:25]([C:27]#[N:28])[C:24]([NH:29][C:30]4[CH:35]=[CH:34][C:33]([C:36]([N:38]5[CH2:43][CH2:42][O:41][CH2:40][CH2:39]5)=[O:37])=[CH:32][CH:31]=4)=[N:23]3)[CH:19]=[CH:20][CH:21]=1)[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+].C[OH:49]>ClCCl.O>[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[C:11](=[O:15])[N:10]([C:16]1[C:17]([CH2:44][OH:45])=[C:18]([N:22]3[CH:26]=[C:25]([C:27]([NH2:28])=[O:49])[C:24]([NH:29][C:30]4[CH:35]=[CH:34][C:33]([C:36]([N:38]5[CH2:39][CH2:40][O:41][CH2:42][CH2:43]5)=[O:37])=[CH:32][CH:31]=4)=[N:23]3)[CH:19]=[CH:20][CH:21]=1)[N:9]=[CH:8]2)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 887Methanol2×HCID 4311764Sodium borohydrideHCID 866737051-(3-(6-tert-Butyl-1-oxophthalazin-2(1H)-yl)-2-formylphenyl)-3-[4-(morpholine-4-carbonyl)phenylamino]pyrazole-4-carbonitrile

Product 1

HCID 710082871-[3-(6-tert-Butyl-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-3-[4-(morpholine-4-carbonyl)-phenylamino]-1H-pyrazole-4-carboxylic acid amide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

1-(3-(6-tert-Butyl-1-oxophthalazin-2(1H)-yl)-2-formylphenyl)-3-[4-(morpholine-4-carbonyl)phenylamino]pyrazole-4-carbonitrile (53 mg, 0.0875 mmol) was dissolved in 6 mL of dichloromethane and 2 mL of methanol. Sodium borohydride solution (8.28 mg, 0.219 mmol) in water (0.5 mL) and methanol (1.0 mL) was added in drops. The mixture was stirred at room temperature for 1 hr. LC/MS showed a clean desired product. The mixture was evaporated to dryness and extracted with dichloromethane and water. The organic layer was dried over sodium sulfate and evaporated to give a pure desired 1-[3-(6-tert-butyl-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl]-3-[4-(morpholine-4-carbonyl)phenylamino]-1H-pyrazole-4-carbonitrile (52.8 mg, 100% yield). LC/MS clacd for C34H33N7O4 (m/e) 603.26, obsd 604.1 (M+H, ES+); 1H NMR (400 MHz, CDCl3) δ ppm 1.47 (s, 9H), 3.61-3.77 (m, 8H), 4.35 (br. s., 2H), 6.59 (br. s., 1H), 7.43 (d, J=8.6 Hz, 2H), 7.50 (d, J=8.1 Hz, 1H), 7.58 (d, J=8.6 Hz, 2H), 7.67 (t, J=8.1 Hz, 1H), 7.80 (d, J=1.7 Hz, 1H), 7.83 (dd, J=8.1, 1.3 Hz, 1H), 7.97 (dd, J=8.6, 1.7 Hz, 1H), 8.39 (d, J=0.5 Hz, 1H), 8.48 (d, J=8.6 Hz, 1H), 8.79 (s, 1H).

Sources & evidence

ORD record
ord-e47812c9561a4decb79d3a8ed437550b
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

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