2,4,5-Trichloropyrimidine → 2-[5-Chloro-2-(1-ethyl-6-methoxy-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-5-methoxy-N-methyl-benzamide

HRID 1040953Notes

Reaction equation

HRID 1040953 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][C:10]=2[C:11]([NH:13][CH3:14])=[O:12])[C:5]([Cl:21])=[CH:4][N:3]=1.NC1C=CC(OC)=CC=1C(NC)=O.ClC1N=C(Cl)C(Cl)=CN=1.[NH2:44][C:45]1[CH:58]=[CH:57][C:48]2[N:49]([CH2:55][CH3:56])[C:50](=[O:54])[CH2:51][CH2:52][CH2:53][C:47]=2[C:46]=1[O:59][CH3:60]>>[Cl:21][C:5]1[C:6]([NH:8][C:9]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][C:10]=2[C:11]([NH:13][CH3:14])=[O:12])=[N:7][C:2]([NH:44][C:45]2[CH:58]=[CH:57][C:48]3[N:49]([CH2:55][CH3:56])[C:50](=[O:54])[CH2:51][CH2:52][CH2:53][C:47]=3[C:46]=2[O:59][CH3:60])=[N:3][CH:4]=1

Participants

5

Reactant 4

HCID 2372592,4,5-TrichloropyrimidineHCID 138538322-amino-5-methoxy-N-methylbenzamideHCID 672642417-Amino-1-ethyl-6-methoxy-1,3,4,5-tetrahydro-benzo[b]azepin-2-oneHCID 866338972-(2,5-Dichloro-pyrimidin-4-ylamino)-5-methoxy-N-methyl-benzamide

Product 1

HCID 668303062-[5-Chloro-2-(1-ethyl-6-methoxy-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-5-methoxy-N-methyl-benzamide

Procedure

2-(2,5-Dichloro-pyrimidin-4-ylamino)-5-methoxy-N-methyl-benzamide, prepared in a similar manner as Example 601a from known 2-amino-5-methoxy-N-methyl-benzamide reacted with 2,4,5-trichloropyrimidine was reacted with 7-Amino-1-ethyl-6-methoxy-1,3,4,5-tetrahydro-benzo[b]azepin-2-one, in a similar manner as Example 601b, to yield crude product 2-[5-Chloro-2-(1-ethyl-6-methoxy-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-5-methoxy-N-methyl-benzamide. The crude material was semi-purified by preparative HPLC, and the purest fractions were partitioned between NaHCO3 and CH2Cl2. The organic phase was dried over Na2SO4, filtered and concentrated under reduced pressure to give a clear oil. This material was dissolved in Et2O and treated with 1N ethereal HCl. The resulting solid was filtered, then dissolved in CH3CN. A solid precipitated with scratching, which was filtered and rinsed with a small amount of ice cold CH3CN to give desired product as a solid HCl salt (4%); 1H NMR (400 MHz, DMSO-d6) δ 11.3 (bs, 1H), 8.74 (bs, 1H), 8.5 (bs, 1H), 8.42 (bd, 1H) 8.18 (s, 1H), 7.74 (d, J=8.84 Hz, 1H), 7.28 (s, 1H), 7.16 (d, J=9.85 Hz), 6.94 (d, J=11.12 Hz, 1H), 3.80 (s, 3H), 3.69 (s, 3H), 2.80 (bs, 3H), 2.23 (bs, 4H), 1.24 (bs, 2H), 1.0 (m, 3H); MS (m/e) 525.49 (M+H).

Sources & evidence

ORD record
ord-f71aecaf78c043d1ae200178677278ac
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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