Dichloromethane → (1R,2R)-2-((6-((9H-purin-9-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol

HRID 1848017Notes

Reaction equation

HRID 1848017 reaction equation
[N:1]1[CH:9]=[C:8]2[C:4]([N:5]([CH2:10][C:11]3[CH:30]=[CH:29][C:14]4[N:15]=[C:16]([N:18]5[C@@H:22]6[CH2:23][CH2:24][CH2:25][CH2:26][C@H:21]6[O:20]C5(C)C)[S:17][C:13]=4[CH:12]=3)[CH:6]=[N:7]2)=[N:3][CH:2]=1.C(Cl)Cl>C(O)(C(F)(F)F)=O>[N:1]1[CH:9]=[C:8]2[C:4]([N:5]([CH2:10][C:11]3[CH:30]=[CH:29][C:14]4[N:15]=[C:16]([NH:18][C@@H:22]5[CH2:23][CH2:24][CH2:25][CH2:26][C@H:21]5[OH:20])[S:17][C:13]=4[CH:12]=3)[CH:6]=[N:7]2)=[N:3][CH:2]=1

Participants

4

Reactant 2

HCID 6344DichloromethaneHCID 86681038(3aR,7aR)-3-(6-((9H-Purin-9-yl)methyl)benzo[d]thiazol-2-yl)-2,2-dimethyloctahydrobenzo[d]oxazole

Product 1

HCID 71550270(1R,2R)-2-((6-((9H-purin-9-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanolYield 4%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of (3aR,7aR)-3-(6-((9H-purin-9-yl)methyl)benzo[d]thiazol-2-yl)-2,2-dimethyloctahydrobenzo[d]oxazole (220 mg, 0.5 mmol) from Step 7 of this Example in TFA (5 mL) and CH2Cl2 (5 mL) was stirred for 2 h at rt. The mixture was concentrated under reduced pressure and the residue was purified by reverse-phase preparative HPLC using a mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C18 column as the stationary phase to afford (1R,2R)-2-((6-((9H-purin-9-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (7 mg, 4%) as a white powder. 1H NMR (300 MHz, DMSO-d6) δ 9.17 (s, 1H), 8.96 (s, 1H), 8.74 (s, 1H), 8.01 (d, J=7.5 Hz, 1H), 7.68 (d, J=1.1 Hz, 1H), 7.17-7.36 (m, 2H), 5.50 (s, 2H), 4.78 (d, J=4.5 Hz, 1H), 3.52 (m, 1H), 3.33 (m, 1H), 2.03 (m, 1H), 1.87 (m, 1H), 1.57-1.67 (m, 2H), 1.11-1.34 (m, 4H). LCMS (ESI) m/z 381 (M+H)+.

Workup

  1. customwas stirred for 2 h at rt
  2. concentrationThe mixture was concentrated under reduced pressure
  3. customthe residue was purified by reverse-phase preparative HPLC
  4. additiona mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C18 column as the stationary phase

Sources & evidence

ORD record
ord-7b45452e42664f6aabec5361a9c162ef
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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