Morpholine → 2-{7-[5-Chloro-4-(2-dimethylsulfamoyl-4-morpholin-4-yl-phenylamino)-pyrimidin-2-ylamino]-8-methoxy-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl}-N,N-dimethyl-acetamide

HRID 1041124Notes

Reaction equation

HRID 1041124 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]([N+:14]([O-])=O)=[C:6](S(N(C)C)(=O)=O)[CH:7]=1.[NH:17]1[CH2:22]COC[CH2:18]1.CN(C)S(C1[CH:33]=[C:32]([N:34]2[CH2:39][CH2:38][O:37][CH2:36][CH2:35]2)C=CC=1[N+]([O-])=O)(=O)=O.NC1C=CC(N2CC[O:54][CH2:53]C2)=CC=1S(N(C)C)(=O)=O.Cl[C:64]1[N:69]=[C:68]([NH:70][C:71]2[CH:76]=[CH:75][C:74]([N:77]3[CH2:82][CH2:81][O:80][CH2:79][CH2:78]3)=[CH:73][C:72]=2[S:83]([N:86]([CH3:88])[CH3:87])(=[O:85])=[O:84])[C:67]([Cl:89])=[CH:66][N:65]=1>>[Cl:89][C:67]1[C:68]([NH:70][C:71]2[CH:76]=[CH:75][C:74]([N:77]3[CH2:78][CH2:79][O:80][CH2:81][CH2:82]3)=[CH:73][C:72]=2[S:83](=[O:84])(=[O:85])[N:86]([CH3:88])[CH3:87])=[N:69][C:64]([NH:14][C:5]2[C:6]([O:54][CH3:53])=[CH:7][C:2]3[CH2:38][CH2:39][N:34]([CH2:35][C:36]([N:17]([CH3:22])[CH3:18])=[O:37])[CH2:32][CH2:33][C:3]=3[CH:4]=2)=[N:65][CH:66]=1

Participants

6

Reactant 5

HCID 8083MorpholineHCID 672635332-Amino-N,N-dimethyl-5-morpholin-4-yl-benzenesulfonamideHCID 672642335-Chloro-N,N-dimethyl-2-nitro-benzenesulfonamideHCID 67264417N,N-Dimethyl-5-morpholin-4-yl-2-nitro-benzenesulfonamideHCID 866339382-(2,5-Dichloro-pyrimidin-4-ylamino)-N,N-dimethyl-5-morpholin-4-yl-benzenesulfonamide

Product 1

HCID 668301612-{7-[5-Chloro-4-(2-dimethylsulfamoyl-4-morpholin-4-yl-phenylamino)-pyrimidin-2-ylamino]-8-methoxy-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl}-N,N-dimethyl-acetamide

Procedure

5-Chloro-N,N-dimethyl-2-nitro-benzenesulfonamide using Morpholine was converted in an analogous manner to Example 171a, to N,N-Dimethyl-5-morpholin-4-yl-2-nitro-benzenesulfonamide, which was converted in an analogous manner to Example 31f, to 2-Amino-N,N-dimethyl-5-morpholin-4-yl-benzenesulfonamide, which was converted, in an analogous procedure to Example 1d, to 2-(2,5-Dichloro-pyrimidin-4-ylamino)-N,N-dimethyl-5-morpholin-4-yl-benzenesulfonamide, which was converted to the title compound in an analogous manner to Example 61e using 2-(7-Amino-8-methoxy-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-N,N-dimethyl-acetamide. Product isolated as a pale yellow foam (0.040 g, 32%). MP: 94-120° C. 1HNMR (400 MHz, CDCl3, δ, ppm): 8.83 (s, 1H), 8.24 (d, 1H, J=8.8 Hz), 8.08 (s, 1H), 8.01 (s, 1H), 7.49 (s, 1H), 7.37 (d, 1H, J=2.5 Hz), 7.10 (dd, 1H, J=8.8 Hz and 2.5 Hz), 6.63 (s, 1H), 3.92-3.87 (m, 4H), 3.86 (s, 3H), 3.27 (s, 2H), 3.22-3.18 (m, 4H), 3.13 (s, 3H), 2.98 (s, 3H), 2.90-2.85 (m, 2H), 2.74-2.63 (m, 13H). MS: 673.21 (MH)+.

Sources & evidence

ORD record
ord-68f1265fcf564bd2975b02643fd9029f
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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