Water → [(1R,2R,3S,4R)-4-({6-[(1S)-2,3-Dihydro-1H-inden-1-ylamino]pyrimidin-4-yl}-amino)-2,3-dihydroxycyclopentyl]methyl sulfamate

HRID 1747567Notes

Reaction equation

HRID 1747567 reaction equation
[S:1](=[O:33])(=[O:32])([O:3][CH2:4][C@@H:5]1[C@@H:12]2[C@@H:8]([O:9]C(C)(C)[O:11]2)[C@H:7]([NH:15][C:16]2[CH:21]=[C:20]([NH:22][C@@H:23]3[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[CH2:25][CH2:24]3)[N:19]=[CH:18][N:17]=2)[CH2:6]1)[NH2:2].FC(F)(F)C(O)=O.O>>[S:1](=[O:33])(=[O:32])([O:3][CH2:4][C@H:5]1[CH2:6][C@@H:7]([NH:15][C:16]2[CH:21]=[C:20]([NH:22][C@@H:23]3[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[CH2:25][CH2:24]3)[N:19]=[CH:18][N:17]=2)[C@H:8]([OH:9])[C@@H:12]1[OH:11])[NH2:2]

Participants

4

Reactant 3

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 86618703[(3aR,4R,6R,6aS)-6-({6-[(1S)-2,3-Dihydro-1H-inden-1-ylamino]pyrimidin-4-yl}-amino)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]methyl sulfamate

Product 1

HCID 59671258[(1R,2R,3S,4R)-4-({6-[(1S)-2,3-Dihydro-1H-inden-1-ylamino]pyrimidin-4-yl}-amino)-2,3-dihydroxycyclopentyl]methyl sulfamateYield 49.2%

Procedure

A solution of [(3aR,4R,6R,6aS)-6-({6-[(1S)-2,3-dihydro-1H-inden-1-ylamino]pyrimidin-4-yl}amino)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-methyl sulfamate (60.0 mg, 0.126 mmol) was treated with a 9:1 mixture of trifluoroacetic acid in H2O (5.00 mL, 58.4 mmol) and the mixture was stirred for 10 min before being concentrated in vacuo. The crude material was purified via reverse phase C18 preparative HPLC eluting with a gradient of 5 to 70% of 0.1% FA/95% ACN/5% H2O in 0.1% FA/99% H2O/1% ACN over 16 min to afford the title compound (27.0 mg, 49%). 1H NMR (400 MHz, DMSO-d6, δ): 8.13 (s, 1H), 7.98 (s, 1H), 7.44 (s, 2H), 7.28-7.02 (m, 5H), 6.72 (bs, 1H), 5.53 (s, 1H), 5.41 (s, 1H), 4.63 (d, J=5.3 Hz, 1H), 4.09 (dd, J=5.1, 9.5 Hz, 1H), 3.97 (dd, J=7.0, 9.5 Hz, 1H), 3.81 (bs, 1H), 3.71-3.60 (m, 2H), 3.01-2.87 (m, 1H), 2.87-2.70 (m, 1H), 2.47-2.37 (m, 1H), 2.30-2.09 (m, 2H), 1.89-1.72 (m, 1H), 1.19-1.05 (m, 1H) ppm. LC/MS: Rt=1.13 min, ES+436 (AA standard).

Workup

  1. concentrationbefore being concentrated in vacuo
  2. customThe crude material was purified via reverse phase C18 preparative HPLC
  3. washeluting with a gradient of 5 to 70% of 0.1%
  4. customover 16 min

Sources & evidence

ORD record
ord-34387481f60e4b868ea6238296aef264
Source dataset
uspto-grants-2015_10
Patent number
US09150525B2

Reaction notes

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