Hydrochloric Acid → HCID 71550848, compound

HRID 1848071Notes

Reaction equation

HRID 1848071 reaction equation
[OH:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9]1[S:10][C:11]2[CH:17]=[C:16]([CH2:18][N:19]3[C:23]4=[N:24][CH:25]=[C:26]([C:28](OC)=[O:29])[CH:27]=[C:22]4[N:21]=[CH:20]3)[CH:15]=[CH:14][C:12]=2[N:13]=1.[H-].C([Al+]CC(C)C)C(C)C.Cl>C(Cl)Cl>[OH:29][CH2:28][C:26]1[CH:27]=[C:22]2[N:21]=[CH:20][N:19]([CH2:18][C:16]3[CH:15]=[CH:14][C:12]4[N:13]=[C:9]([NH:8][C@@H:3]5[CH2:4][CH2:5][CH2:6][CH2:7][C@H:2]5[OH:1])[S:10][C:11]=4[CH:17]=3)[C:23]2=[N:24][CH:25]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 21225700DiisobutylaluminumhydrideHCID 71550846HCID 71550846, compound

Product 1

HCID 71550848HCID 71550848, compoundYield 28.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-20 °C

Procedure

To a stirred mixture of methyl 3-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]thiazol-6-yl)methyl)-3H-imidazo[4,5-b]pyridine-6-carboxylate (76 mg, 0.174 mmol) from Example 79 in anhydrous DCM (1 mL) at −50° C. under argon was added dropwise diisobutylaluminum hydride (1 M solution in DCM, 0.696 μL, 696 mmol). The mixture was allowed to warm to −20° C. and stirred for 10 min. The reaction mixture was acidified to pH˜1.0 with 2 M aq HCl, and the mixture was purified directly by reverse-phase HPLC using a mixture of water (5% CH3CN, 0.05% HOAc) and CH3CN (0.05% HOAc) as the mobile phase and Varian Pursuit XRs diphenyl column as the stationary phase to afford (1R,2R)-2-((6-((6-(hydroxymethyl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (20 mg, 28%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.56 (s, 1H), 8.35 (d, J=1.3 Hz, 1H), 7.93-8.01 (m, 2H), 7.65 (s, 1H), 7.28 (m, 1H), 7.20 (m, 1H), 5.47 (s, 2H), 5.29 (br s, 1H), 4.75 (d, J=4.0 Hz, 1H), 4.62 (br s, 2H), 3.50 (m, 1H), 3.30 (m, 1H), 2.03 (m, 1H), 1.87 (m, 1H), 1.55-1.65 (m, 2H), 1.10-1.35 (m, 4H). LCMS (ESI) m/z 410 (M+H)+.

Workup

  1. customthe mixture was purified directly by reverse-phase
  2. additiona mixture of water (5% CH3CN, 0.05% HOAc) and CH3CN (0.05% HOAc) as the mobile phase and Varian Pursuit XRs diphenyl column as the stationary phase

Sources & evidence

ORD record
ord-d041cba49dff48e9b676da77d66b649d
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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