Morpholine → 2-{7-[5-Chloro-4-(2-methyl-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 1041100Notes

Reaction equation

HRID 1041100 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-])=O)=[C:4](C)[CH:3]=1.[NH:12]1[CH2:17]COC[CH2:13]1.CC1C=[C:21]([N:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)[CH:22]=CC=1[N+]([O-])=O.CC1C=C(N2CC[O:44][CH2:43]C2)C=CC=1N.Cl[C:49]1[N:54]=[C:53]([NH:55][C:56]2[CH:61]=[CH:60][C:59]([N:62]3[CH2:67][CH2:66][O:65][CH2:64][CH2:63]3)=[CH:58][C:57]=2[CH3:68])[C:52]([Cl:69])=[CH:51][N:50]=1>>[Cl:69][C:52]1[C:53]([NH:55][C:56]2[CH:61]=[CH:60][C:59]([N:62]3[CH2:67][CH2:66][O:65][CH2:64][CH2:63]3)=[CH:58][C:57]=2[CH3:68])=[N:54][C:49]([NH:8][C:5]2[C:4]([O:44][CH3:43])=[CH:3][C:2]3[CH2:32][CH2:33][N:28]([CH2:29][C:30]([N:12]([CH3:17])[CH3:13])=[O:31])[CH2:21][CH2:22][C:7]=3[CH:6]=2)=[N:50][CH:51]=1

Participants

6

Reactant 5

HCID 8083MorpholineHCID 949565-Fluoro-2-nitrotolueneHCID 112645284-(3-Methyl-4-nitrophenyl)morpholineHCID 219550002-Methyl-4-(morpholin-4-yl)anilineHCID 86633931(2,5-Dichloro-pyrimidin-4-yl)-(2-methyl-4-morpholin-4-yl-phenyl)-amine

Product 1

HCID 668302872-{7-[5-Chloro-4-(2-methyl-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

4-Fluoro-2-methyl-1-nitro-benzene using Morpholine was converted in an analogous manner to Example 171b, to 4-(3-Methyl-4-nitro-phenyl)-morpholine which was converted in an analogous manner to Example 31f, to 2-Methyl-4-morpholin-4-yl-phenylamine, which was converted in an analogous manner to Example 1d, to (2,5-Dichloro-pyrimidin-4-yl)-(2-methyl-4-morpholin-4-yl-phenyl)-amine 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 (54.0 mg, 0.000194 mol). Product isolated as an off-white solid (0.040 g, 39%). MP: 223-226° C. 1HNMR (400 MHz, CDCl3, δ, ppm): 8.00 (d, 1H, J=1.0 Hz), 7.86 (s, 1H), 7.52-7.45 (m, 2H), 6.83-6.76 (m, 2H), 6.68 (s, 1H), 6.57 (s, 1H), 3.91-3.86 (m, 4H), 3.82 (s, 3H), 3.25 (s, 2H), 3.20-3.13 (m, 7H), 2.99 (s, 3H), 2.85-2.80 (m, 2H), 2.67-2.56 (m, 6H), 2.26 (s, 3H). MS: 580.29 (MH)+.

Sources & evidence

ORD record
ord-511b9cc5a30a4b13aadeb563eb83352c
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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