Pyridine → {(1R,2R,4S)-2-hydroxy-4-[(6-{[(1S,2R)-2-methoxy-2,3-dihydro-1H-inden-1-yl]-amino}pyrimidin-4-yl)amino]cyclopentyl}methyl sulfamate

HRID 1677965Notes

Reaction equation

HRID 1677965 reaction equation
[Si]([O:8][C@@H:9]1[CH2:13][C@@H:12]([NH:14][C:15]2[CH:20]=[C:19]([NH:21][C@H:22]3[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[CH2:24][C@H:23]3[O:31][CH3:32])[N:18]=[CH:17][N:16]=2)[CH2:11][C@@H:10]1[CH2:33][OH:34])(C(C)(C)C)(C)C.N1C=CC=CC=1.Cl[S:42]([NH2:45])(=[O:44])=[O:43]>C(#N)C>[S:42](=[O:44])(=[O:43])([O:34][CH2:33][C@H:10]1[CH2:11][C@H:12]([NH:14][C:15]2[CH:20]=[C:19]([NH:21][C@H:22]3[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[CH2:24][C@H:23]3[O:31][CH3:32])[N:18]=[CH:17][N:16]=2)[CH2:13][C@H:9]1[OH:8])[NH2:45]

Participants

5

Reactant 3

HCID 1049Pyridine2×HCID 24499Chlorosulfamic acid2×HCID 66797967{(1R,2R,4S)-2-{[tert-butyl(dimethyl)silyl]oxy}-4-[(6-{[(1S,2R)-2-methoxy-2,3-dihydro-1H-inden-1-yl]amino}pyrimidin-4-yl)amino]cyclopentyl}methanol

Product 1

HCID 86618717{(1R,2R,4S)-2-hydroxy-4-[(6-{[(1S,2R)-2-methoxy-2,3-dihydro-1H-inden-1-yl]-amino}pyrimidin-4-yl)amino]cyclopentyl}methyl sulfamateYield 57%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent3×

Procedure

A solution of {(1R,2R,4S)-2-{[tert-butyl(dimethyl)silyl]oxy}-4-[(6-{[(1S,2R)-2-methoxy-2,3-dihydro-1H-inden-1-yl]amino}pyrimidin-4-yl)amino]cyclopentyl}methanol (0.112 g, 0.231 mmol) (azetroped with toluene) and pyridine (0.0374 mL, 0.462 mmol) in anhydrous acetonitrile (2.3 mL) was cooled to 0° C. A 2 N solution of chlorosulfonamide in acetonitrile (0.116 mL) was added dropwise and the reaction was stirred for 3 h. Additional 2 N solution of chlorosulfonamide in acetonitrile (0.026 mL) and pyridine (0.0041 g, 0.052 mol) were added and the reaction was stirred for 1 h then quenched with methanol. The solution was concentrated in vacuo and purified by flash chromatography (0 to 10% MeOH/DCM) to afford the title compound as a white solid (0.059 g, 57%). 1H NMR (CD3OD, 400 MHz, δ): 8.26 (s, 1H); 8.01 (s, 1H); 7.26-7.16 (m, 3H); 5.70 (s, 1H); 5.47-5.33 (bs, 1H); 4.35 (t, J=4.5 Hz, 1H); 4.31 (d, J=7.5 Hz, 1H); 4.28 (d, J=7.5 Hz, 1H); 4.25-4.21 (m, 1H); 4.15-4.11 (dd, J=7.3 Hz; J=2.5 Hz, 1H); 3.36 (s, 3H); 3.16-3.00 (m, 2H); 2.54-2.45 (m, 1H); 2.26-2.19 (m, 1H); 2.10-1.98 (m, 1H); 1.87-1.78 (m, 1H); 1.77-1.69 (m, 1H). LC/MS: Rt=1.11 min, ES+ 450 (FA standard).

Workup

  1. stirringthe reaction was stirred for 1 h
  2. customthen quenched with methanol
  3. concentrationThe solution was concentrated in vacuo
  4. custompurified by flash chromatography (0 to 10% MeOH/DCM)

Sources & evidence

ORD record
ord-568e9b0cc43e4482a415d7d6986c6b46
Source dataset
uspto-grants-2011_08
Patent number
US08008307B2

Reaction notes

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