Hydrochloric Acid → N-[((1S,2S,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-2-hydroxycyclopentyl)methyl]-N-methylsulfamide

HRID 222210Notes

Reaction equation

HRID 222210 reaction equation
[Si]([O:8][C@H:9]1[CH2:13][C@H:12]([N:14]2[C:18]3[N:19]=[CH:20][N:21]=[C:22]([NH:23][C@@H:24]4[C:32]5[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=5)[CH2:26][CH2:25]4)[C:17]=3[CH:16]=[CH:15]2)[CH2:11][C@H:10]1[CH2:33][N:34]([CH3:39])[S:35]([NH2:38])(=[O:37])=[O:36])(C(C)(C)C)(C)C.C(O)C.Cl>O1CCCC1.O>[C@@H:24]1([NH:23][C:22]2[C:17]3[CH:16]=[CH:15][N:14]([C@@H:12]4[CH2:11][C@@H:10]([CH2:33][N:34]([CH3:39])[S:35]([NH2:38])(=[O:37])=[O:36])[C@@H:9]([OH:8])[CH2:13]4)[C:18]=3[N:19]=[CH:20][N:21]=2)[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH2:26][CH2:25]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 702EthanolHCID 58944658N-[((1S,2S,4R)-2-[tert-butyl(dimethyl)silyl]oxy-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}cyclopentyl)methyl]-N-methylsulfamide

Product 1

HCID 58944568N-[((1S,2S,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-2-hydroxycyclopentyl)methyl]-N-methylsulfamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

N-[((1S,2S,4R)-2-[tert-Butyl(dimethyl)silyl]oxy-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}cyclopentyl)methyl]-N-methylsulfamide (25.0 mg, 0.0000438 mol) was dissolved in tetrahydrofuran (2.0 mL), ethanol (2.0 mL) and 1.00 M of hydrochloric acid in water (2.0 mL). The mixture was stirred overnight at room temperature. The solution was evaporated to dryness, and the residue was dissolved in methanol and treated with a 7.00 M solution of ammonia in methanol (0.1 mL). Solvents were again evaporated, and the residue was purified by silica gel chromatography, eluting with 2 to 10% methanol in dichloromethane to yield the product, 9.8 mg (49%). 1H-NMR (400 MHz, MeOD) δ 8.16 (s, 1H), 7.19 (m, 5H), 6.62 (d, 1H, J=3.6 Hz), 5.84 (t, J=7.7 Hz, 1H), 5.43 (ddd, J=4.5 Hz, 8.6 Hz, 12.8 Hz, 1H), 4.43 (t, J=3.7 Hz, 1H), 3.25 (dd, J=8.1 Hz, 13.7 Hz, 1H), 3.14 (dd, J=7.2 Hz, 13.7 Hz, 1H), 3.05 (ddd, J=3.3 Hz, 8.8 Hz, 15.8 Hz, 1H), 2.91 (m, 1H), 2.74 (m, 1H, 2.63 (m, 1H), 2.34 (ddd, J=1.1 Hz, 7.8 Hz, 13.6 Hz, 1H), 2.20 (m, 2H, 1.99 (m, 2H). LC/MS: Rt=1.51 min, ES+ 457 (AA standard).

Workup

  1. customThe solution was evaporated to dryness
  2. dissolutionthe residue was dissolved in methanol
  3. additiontreated with a 7.00 M solution of ammonia in methanol (0.1 mL)
  4. customSolvents were again evaporated
  5. customthe residue was purified by silica gel chromatography
  6. washeluting with 2 to 10% methanol in dichloromethane
  7. customto yield the product, 9.8 mg (49%)

Sources & evidence

ORD record
ord-fe5c2752cf1745c1b155c8c2b2759e1d
Source dataset
uspto-grants-2012_06
Patent number
US08207177B2

Reaction notes

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