Triethylamine → N-((1R,2S)-2-{5-Chloro-2-[3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-cyclopentyl)-methanesulfonamide

HRID 1687839Notes

Reaction equation

HRID 1687839 reaction equation
[NH2:1][C@@H:2]1[CH2:6][CH2:5][CH2:4][C@@H:3]1[NH:7][C:8]1[C:13]([Cl:14])=[CH:12][N:11]=[C:10]([NH:15][C:16]2[CH:30]=[CH:29][C:19]3[CH2:20][CH2:21][N:22]([CH2:25][CH2:26][O:27][CH3:28])[CH2:23][CH2:24][C:18]=3[CH:17]=2)[N:9]=1.CCN(CC)CC.[CH3:38][S:39](Cl)(=[O:41])=[O:40]>C(Cl)Cl>[Cl:14][C:13]1[C:8]([NH:7][C@H:3]2[CH2:4][CH2:5][CH2:6][C@H:2]2[NH:1][S:39]([CH3:38])(=[O:41])=[O:40])=[N:9][C:10]([NH:15][C:16]2[CH:30]=[CH:29][C:19]3[CH2:20][CH2:21][N:22]([CH2:25][CH2:26][O:27][CH3:28])[CH2:23][CH2:24][C:18]=3[CH:17]=2)=[N:11][CH:12]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 131729607N*4*-((1S,2R)-2-Amino-cyclopentyl)-5-chloro-N*2*-[3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl]-pyrimidine-2,4-diamine

Product 1

HCID 66830298N-((1R,2S)-2-{5-Chloro-2-[3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-cyclopentyl)-methanesulfonamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of N*4*-((1S,2R)-2-Amino-cyclopentyl)-5-chloro-N*2*-[3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl]-pyrimidine-2,4-diamine (132 mg, 0.298 mmol) in DCM (2 mL) was added Et3N (62.0 μL, 0.447 mmol) at 0° C. under argon. Stirred reaction for 10 min. before adding methanesulfonyl chloride (34.6 μL, 0.447 mmol) dropwise via syringe. Reaction stirred for 20 minutes at 0° C. The reaction mixture was diluted with DCM and washed with 1N NaOH (2×). Dried organic layer over MgSO4, filtered and concentrated. The residue was purified by column chromatography to yield (58 mg, 38%). mp: 73-74° C., MS (ESI+): 509 (M+H), 1H-NMR (CDCl3, 400 MHz) δ 9.14 (s, 1H), 7.97 (s, 1H), 7.51 (s, 1H), 1.33 (d, J=7.5 Hz, 1H), 7.32 (s, 1H), 6.96 (d, J=8 Hz, 1H), 6.40 (d, J=7 Hz, 1H), 4.34 (m, 1H), 3.89 (br s, 1H), 3.44 (t, J=6 Hz, 2H), 3.23 (s, 3H), 2.75 (br s, 8H), 2.62 (m, 8H), 2.50 (m, 5H), 2.02 (m, 2H), 1.76 (m, 2H), 1.66 (m, 1H), 1.54 (m, 2H).

Workup

  1. customreaction for 10 min.
  2. customReaction
  3. stirringstirred for 20 minutes at 0° C
  4. washwashed with 1N NaOH (2×)
  5. filtrationDried organic layer over MgSO4, filtered
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography
  8. customto yield (58 mg, 38%)

Sources & evidence

ORD record
ord-d8948676325941939fc5e63a470fa5c0
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

Loading…