D-Camphorsulfonic Acid → 2-[5-Chloro-2-(1-oxo-2,3,4,5-tetrahydro-1H-benzo[c]azepin-8-ylamino)-pyrimidin-4-ylamino]-3,N-dimethyl-benzamide

HRID 1687198Notes

Reaction equation

HRID 1687198 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[C:18]([CH3:19])=[CH:17][CH:16]=[CH:15][C:10]=2[C:11]([NH:13][CH3:14])=[O:12])[C:5]([Cl:20])=[CH:4][N:3]=1.[NH2:21][C:22]1[CH:23]=[CH:24][C:25]2[CH2:31][CH2:30][CH2:29][NH:28][C:27](=[O:32])[C:26]=2[CH:33]=1.CC1(C)[C@]2(CS(O)(=O)=O)C(C[C@H]1CC2)=O>C(O)(C)C>[Cl:20][C:5]1[C:6]([NH:8][C:9]2[C:18]([CH3:19])=[CH:17][CH:16]=[CH:15][C:10]=2[C:11]([NH:13][CH3:14])=[O:12])=[N:7][C:2]([NH:21][C:22]2[CH:23]=[CH:24][C:25]3[CH2:31][CH2:30][CH2:29][NH:28][C:27](=[O:32])[C:26]=3[CH:33]=2)=[N:3][CH:4]=1

Participants

5

Reactant 3

HCID 65617D-Camphorsulfonic AcidHCID 672647208-amino-2,3,4,5-tetrahydro-1H-2-benzazepin-1-oneHCID 866338742-(2,5-dichloropyrimidin-4-ylamino)-N,3-dimethylbenzamide

Product 1

HCID 668305022-[5-Chloro-2-(1-oxo-2,3,4,5-tetrahydro-1H-benzo[c]azepin-8-ylamino)-pyrimidin-4-ylamino]-3,N-dimethyl-benzamideYield 17.3%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

Combined 2-(2,5-Dichloro-pyrimidin-4-ylamino)-3,N-dimethyl-benzamide (100 mg, 0.321 mmol), 8-Amino-2,3,4,5-tetrahydro-benzo[c]azepin-1-one (69 mg, 0.392 mmol), DL-10-Camphorsulfonic acid (93 mg, 0.400 mmol) and isopropanol (4 mL) in a microwave tube. Microwaved reaction at 120° C. for 30 minutes. Evaporated off solvent and purified with normal phase chromatography to yield an off-white solid, 2-[5-Chloro-2-(1-oxo-2,3,4,5-tetrahydro-1H-benzo[c]azepin-8-ylamino)-pyrimidin-4-ylamino]-3,N-dimethyl-benzamide (25 mg, 17%). mp 259° C.; LCMS: m/z=451.36 (M+H+), 1H NMR (400 MHz, CD3OD) δ 8.02 (s, 1H), 7.69 (m, 1H), 7.58 (s, 1H), 7.42 (m, 2H), 7.37 (m, 1H), 7.30 (m, 1H), 6.97 (d, 1H, J=8.3 Hz), 4.24 (m, 1H), 3.50 (m, 1H), 3.15 (m, 1H), 3.02 (m, 2H), 2.82 (s, 3H), 2.73 (m, 2H), 2.24 (s, 3H), 1.97 (m, 2H).

Workup

  1. customMicrowaved
  2. customreaction at 120° C. for 30 minutes
  3. customEvaporated off solvent
  4. custompurified with normal phase chromatography

Sources & evidence

ORD record
ord-a8c13f11988743529616f5ed5d2c3297
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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