2-((1,1-Dimethylethyl)imino)-N,N-diethylhexahydro-1,3-dimethyl-2lambda5-1,3,2-diazaphosphorin-2-amine → Methyl 5-chloro-2-(4-(dimethylamino)benzamido)-4-(4-(3-(2-methoxyphenyl)-5-methylisoxazole-4-carbonyl)piperazin-1-yl)benzoate

HRID 1808897Notes

Reaction equation

HRID 1808897 reaction equation
[NH2:1][C:2]1[CH:11]=[C:10]([N:12]2[CH2:17][CH2:16][N:15]([C:18]([C:20]3[C:21]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=4[O:32][CH3:33])=[N:22][O:23][C:24]=3[CH3:25])=[O:19])[CH2:14][CH2:13]2)[C:9]([Cl:34])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[CH3:35][N:36]([CH3:46])[C:37]1[CH:45]=[CH:44][C:40]([C:41](Cl)=[O:42])=[CH:39][CH:38]=1.C(N=P1(N(CC)CC)N(C)CCCN1C)(C)(C)C>CN(C)C1C=CN=CC=1.ClCCCl>[Cl:34][C:9]1[C:10]([N:12]2[CH2:13][CH2:14][N:15]([C:18]([C:20]3[C:21]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=4[O:32][CH3:33])=[N:22][O:23][C:24]=3[CH3:25])=[O:19])[CH2:16][CH2:17]2)=[CH:11][C:2]([NH:1][C:41](=[O:42])[C:40]2[CH:39]=[CH:38][C:37]([N:36]([CH3:35])[CH3:46])=[CH:45][CH:44]=2)=[C:3]([CH:8]=1)[C:4]([O:6][CH3:7])=[O:5]

Participants

6

Reactant 3

HCID 35138512-((1,1-Dimethylethyl)imino)-N,N-diethylhexahydro-1,3-dimethyl-2lambda5-1,3,2-diazaphosphorin-2-amineHCID 44007824-(Dimethylamino)benzoyl chlorideHCID 66691522Methyl 2-amino-5-chloro-4-(4-(3-(2-methoxyphenyl)-5-methylisoxazole-4-carbonyl)piperazin-1-yl)benzoate

Product 1

HCID 66692078Methyl 5-chloro-2-(4-(dimethylamino)benzamido)-4-(4-(3-(2-methoxyphenyl)-5-methylisoxazole-4-carbonyl)piperazin-1-yl)benzoateYield 69.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 111,2-DichloroethaneSolvent

Conditions

Temperature
80 °C

Procedure

The reaction mixture of methyl 2-amino-5-chloro-4-(4-(3-(2-methoxyphenyl)-5-methylisoxazole-4-carbonyl)piperazin-1-yl)benzoate (27.5 mg, 0.057 mmol), 4-(dimethylamino)benzoyl chloride (52.1 mg, 0.284 mmol), N,N-dimethylpyridin-4-amine (0.693 mg, 5.67 μmol) and 2-tert-Butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,3,2-diazaphosphorine (78 mg, 0.284 mmol) in DCE (1.5 mL) was stirred at 80° C. for 6 hours. The product was purified by preparative HPLC (0.1% TFA MeOH/H2O) to give 25 mg (49% yield) of methyl 5-chloro-2-(4-(dimethylamino)benzamido)-4-(4-(3-(2-methoxyphenyl)-5-methylisoxazole-4-carbonyl)piperazin-1-yl)benzoate. 1H-NMR (CDCl3, 400 MHz): δ 12.06 (1H, s), 8.53 (1H, s), 8.05-7.99 (3H, m), 7.59 (1H, dd, J1=7.5 Hz, J2=1.5 Hz), 7.53-7.46 (1H, m), 7.15-6.99 (4H, m), 3.95 (3H, s), 3.84 (2H, s), 3.82 (3H, s), 3.28 (2H, s), 3.15 (6H, s), 2.59 (3H, s).

Workup

  1. customThe product was purified by preparative HPLC (0.1% TFA MeOH/H2O)

Sources & evidence

ORD record
ord-5787ffb0bebb4bec9dd1aa0ec89a124a
Source dataset
uspto-grants-2013_01
Patent number
US08362004B2

Reaction notes

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