2,6-Di-tert-butyl-4-methylpyridine → [(1R,2S,4R)-4-({6-[(1S)-2,3-Dihydro-1H-inden-1-ylamino]pyrimidin-4-yl}-amino)-2-hydroxycyclopentyl]methyl sulfamate

HRID 1677925Notes

Reaction equation

HRID 1677925 reaction equation
[C@@H:1]1([NH:10][C:11]2[N:16]=[CH:15][N:14]=[C:13]([NH:17][C@H:18]3[CH2:22][C@H:21]([OH:23])[C@@H:20]([CH2:24][OH:25])[CH2:19]3)[CH:12]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.C(C1C=C(C)C=C(C(C)(C)C)N=1)(C)(C)C.Cl[S:42]([NH:45]C(=O)OC(C)(C)C)(=[O:44])=[O:43]>C(#N)C>[S:42](=[O:44])(=[O:43])([O:25][CH2:24][C@H:20]1[CH2:19][C@@H:18]([NH:17][C:13]2[CH:12]=[C:11]([NH:10][C@@H:1]3[C:9]4[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=4)[CH2:3][CH2:2]3)[N:16]=[CH:15][N:14]=2)[CH2:22][C@@H:21]1[OH:23])[NH2:45]

Participants

5

Reactant 3

HCID 988982,6-Di-tert-butyl-4-methylpyridineHCID 15677406tert-butyl N-(chlorosulfonyl)carbamateHCID 66797896HCID 66797896, compound

Product 1

HCID 24829705[(1R,2S,4R)-4-({6-[(1S)-2,3-Dihydro-1H-inden-1-ylamino]pyrimidin-4-yl}-amino)-2-hydroxycyclopentyl]methyl sulfamateYield 40.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A neat mixture of (1S,2R,4R)-4-({6-[(1S)-2,3-dihydro-1H-inden-1-ylamino]pyrimidin-4-yl}amino)-2-(hydroxymethyl)cyclopentanol (100. mg, 0.294 mmol) and 2,6-di-tert-butyl-4-methylpyridine (181 mg, 0.881 mmol) was dissolved in ACN (5.00 mL) before tert-butyl (chlorosulfonyl)carbamate (95.0 mg, 0.441 mmol, as prepared in Example 21c) was added. The reaction was stirred for 2 h before being quenched via addition of MeOH (2 mL). The resulting mixture was concentrated in vacuo and purified via silica gel chromatography eluting with a gradient of 10 to 20% MeOH in DCM to afford the title compound as an amorphous solid (50.0 mg, 33%). LC/MS: Rt=1.24 min, ES+ 520. (AA standard).

Workup

  1. additionwas added
  2. custombefore being quenched via addition of MeOH (2 mL)
  3. concentrationThe resulting mixture was concentrated in vacuo
  4. custompurified via silica gel chromatography
  5. washeluting with a gradient of 10 to 20% MeOH in DCM

Sources & evidence

ORD record
ord-4a05b46a9084475baa2cf3801c1bae45
Source dataset
uspto-grants-2011_08
Patent number
US08008307B2

Reaction notes

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