Hydrochloric Acid → N-[(1R,2R)-2-[[5-chloro-2-[[7-methoxy-3-(2-methoxyethyl)-1,2,4,5-tetrahydro-3-benzazepin-8-yl]amino]pyrimidin-4-yl]amino]cyclohexyl]methanesulfonamide

HRID 1040645노트

반응식

HRID 1040645 반응식
[CH3:1][O:2][C:3]1[C:4]([NH2:18])=[CH:5][C:6]2[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][O:15][CH3:16])[CH2:9][CH2:8][C:7]=2[CH:17]=1.Cl[C:20]1[N:25]=[C:24]([NH:26][C@@H:27]2[CH2:32][CH2:31][CH2:30][CH2:29][C@H:28]2[NH:33][S:34]([CH3:37])(=[O:36])=[O:35])[C:23]([Cl:38])=[CH:22][N:21]=1.Cl.C(O)(C)C.CC[NH+](CC)CC.CC[NH+](CC)CC.C([O-])([O-])=O>O1CCOCC1>[Cl:38][C:23]1[C:24]([NH:26][C@@H:27]2[CH2:32][CH2:31][CH2:30][CH2:29][C@H:28]2[NH:33][S:34]([CH3:37])(=[O:36])=[O:35])=[N:25][C:20]([NH:18][C:4]2[C:3]([O:2][CH3:1])=[CH:17][C:7]3[CH2:8][CH2:9][N:10]([CH2:13][CH2:14][O:15][CH3:16])[CH2:11][CH2:12][C:6]=3[CH:5]=2)=[N:21][CH:22]=1

참가 물질

7

반응물 5

HCID 313Hydrochloric AcidHCID 3776IsopropanolHCID 15264167Carbonic acid--N,N-diethylethanamine (1/2)HCID 574161508-Methoxy-3-(2-methoxyethyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-7-amineHCID 86633854N-[(1R,2R)-2-(2,5-dichloropyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide

생성물 1

HCID 53482132N-[(1R,2R)-2-[[5-chloro-2-[[7-methoxy-3-(2-methoxyethyl)-1,2,4,5-tetrahydro-3-benzazepin-8-yl]amino]pyrimidin-4-yl]amino]cyclohexyl]methanesulfonamide

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

반응 조건

온도
130 °C

실험 절차

8-Methoxy-3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine (165 mg, 0.000659 mol), N-[(1R,2R)-2-(2,5-Dichloro-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide (220 mg, 0.00066 mol), 4 M of Hydrogen chloride in 1,4-Dioxane (200 uL) and Isopropyl alcohol (6.6 mL, 0.086 mol;) were combined in a microwave vessel. Heat at 130° C. for 20 min. The mixture was treated with 500 mgs of MP-carbonate resin and stirred for 20 min. The mixture was filtered and concentrated and put on high vac overnight. The crude solid was dissolved in DCM and purified on an ISCO column (40 g, SiO2, 100% DCM to MeOH/DCM gradient) to afford N-((1R,2R)-2-{5-Chloro-2-[8-methoxy-3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonam (99 mg, 48%). MP: 92-94° C. 1H-NMR (CDCl3, 400 MHz): 1H-NMR (CDCL3) δ 7.96 (s, 1H), 7.32 (s, 1H), 6.67 (s, 1H), 5.37-5.31 (m, 2H), 3.99-3.95 (broad m, 1H), 3.88 (s, 1H), 3.56 (br s, 2H), 3.38 (s, 1H), 3.28-3.24 (m, 1H), 2.99-2.70 (complex series of m, 11H), 2.26-2.20 (m, 2H), 1.88-1.80 (m, 2H), 1.41-1.28 (m, 6H), 0.92-0.85 (m, 2H); LC/MS: 552.92 (M+H).

후처리

  1. filtrationThe mixture was filtered
  2. concentrationconcentrated
  3. waitput on high vac overnight
  4. dissolutionThe crude solid was dissolved in DCM
  5. custompurified on an ISCO column (40 g, SiO2, 100% DCM to MeOH/DCM gradient)
  6. customto afford N-((1R,2R)-2-{5-Chloro-2-[8-methoxy-3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonam (99 mg, 48%)

출처 및 근거

ORD 기록
ord-d1432202d6b34a168c28b5b226703b0b
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08552186B2

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