Hydrochloric Acid → HCID 67264489, compound

HRID 1687816Notes

Reaction equation

HRID 1687816 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[C:11](=[O:12])[NH:10][CH2:9][CH2:8][N:7]([CH2:13][CH3:14])[C:6]=2[CH:15]=1.Cl[C:17]1[N:22]=[C:21]([NH:23][C@@H:24]2[CH2:29][CH2:28][CH2:27][CH2:26][C@H:25]2[NH:30][S:31]([CH3:34])(=[O:33])=[O:32])[C:20]([Cl:35])=[CH:19][N:18]=1.Cl.C(=O)([O-])[O-]>O1CCOCC1.CO.COCCO>[Cl:35][C:20]1[C:21]([NH:23][C@@H:24]2[CH2:29][CH2:28][CH2:27][CH2:26][C@H:25]2[NH:30][S:31]([CH3:34])(=[O:33])=[O:32])=[N:22][C:17]([NH:1][C:2]2[CH:3]=[CH:4][C:5]3[C:11](=[O:12])[NH:10][CH2:9][CH2:8][N:7]([CH2:13][CH3:14])[C:6]=3[CH:15]=2)=[N:18][CH:19]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 19660Carbonate IonHCID 67263949HCID 67263949, compoundHCID 86633854N-[(1R,2R)-2-(2,5-dichloropyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide

Product 1

HCID 67264489HCID 67264489, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 80192-MethoxyethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

Into a microwave vial, 8-amino-1-ethyl-1,2,3,4-tetrahydro-benzo[e][1,4]diazepin-5-one (75 mg, 0.00036 mol), N-[(1R,2R)-2-(2,5-dichloro-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide (113 mg, 0.332 mmol), 4 M of hydrogen chloride in dioxane (0.2 mL), and 2-methoxyethanol (2.3 mL) were added. The reaction was then heated in microwave at 120 degree Celsius for one hour. MP-carbonate (3.16 mmol/g loading; 263 mg, 0.83 mmole) and methanol (10 mL) were added. The mixture was stirred at room temperature over night. The solid was filtered and washed with methanol. The desired product was isolated via column chromatography with DCM and methanol as eluant. The collected fractions afforded N-{(1R,2R)-2-[5-Chloro-2-(1-ethyl-5-oxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-8-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide as a yellow solid (35 mg, 19%). 1H-NMR (DMSO-D6, 400 MHz): δ 9.19 (s, 1H), 7.94 (s, 1H), 7.51 (d, 1H), 7.12 (d, 1H), 7.07 (d, 1H), 6.97 (s, 1H), 6.75 (d, 1H), 5.99 (bs, 1H), 3.70-3.88 (m, 1H), 3.25-3.52 (m, 7H), 2.92 (s, 3H), 1.97-2.10 (m, 2H), 1.69 (bs, 2H), 1.15-1.48 (m, 4H), 1.08 (t, 3H) LCMS (ESI+) 508.26 (M+H). MP 216-220° C.

Workup

  1. temperatureThe reaction was then heated in microwave at 120 degree Celsius for one hour
  2. filtrationThe solid was filtered
  3. washwashed with methanol

Sources & evidence

ORD record
ord-1f0ac92fea3d4d288d7e548186d9162c
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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