2,6-Di-tert-butyl-4-methylpyridine → tert-butyl ({[(1R,2S,4R)-4-({6-[(1S)-2,3-dihydro-1H-inden-1-ylamino]pyrimidin-4-yl}amino)-2-hydroxycyclopentyl]methoxy}sulfonyl)carbamate

HRID 1397523Notes

Reaction equation

HRID 1397523 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:46](=[O:52])[O:47][C:48]([CH3:51])([CH3:50])[CH3:49])(=[O:44])=[O:43]>C(#N)C>[C@@H:1]1([NH:10][C:11]2[N:16]=[CH:15][N:14]=[C:13]([NH:17][C@@H:18]3[CH2:19][C@H:20]([CH2:24][O:25][S:42]([NH:45][C:46](=[O:52])[O:47][C:48]([CH3:50])([CH3:49])[CH3:51])(=[O:43])=[O:44])[C@@H:21]([OH:23])[CH2:22]3)[CH:12]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

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

Product 1

HCID 86618704tert-butyl ({[(1R,2S,4R)-4-({6-[(1S)-2,3-dihydro-1H-inden-1-ylamino]pyrimidin-4-yl}amino)-2-hydroxycyclopentyl]methoxy}sulfonyl)carbamateYield 33%

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-33ad81d06f3249fe99eb9b1125975b7c
Source dataset
uspto-grants-2014_12
Patent number
US08901136B2

Reaction notes

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