Diisopropylethylamine → HCID 71550846, compound

HRID 1848067Notes

Reaction equation

HRID 1848067 reaction equation
CS([C:4]1[S:5][C:6]2[CH:12]=[C:11]([CH2:13][N:14]3[C:18]4=[N:19][CH:20]=[C:21]([C:23]([O:25][CH3:26])=[O:24])[CH:22]=[C:17]4[N:16]=[CH:15]3)[CH:10]=[CH:9][C:7]=2[N:8]=1)=O.CS(C1SC2C=C(CN3C4=NC=C(C(OC)=O)C=C4N=C3)C=CC=2N=1)(=O)=O.[NH2:54][C@@H:55]1[CH2:60][CH2:59][CH2:58][CH2:57][C@H:56]1[OH:61].CCN(C(C)C)C(C)C>CC(N(C)C)=O>[OH:61][C@@H:56]1[CH2:57][CH2:58][CH2:59][CH2:60][C@H:55]1[NH:54][C:4]1[S:5][C:6]2[CH:12]=[C:11]([CH2:13][N:14]3[C:18]4=[N:19][CH:20]=[C:21]([C:23]([O:25][CH3:26])=[O:24])[CH:22]=[C:17]4[N:16]=[CH:15]3)[CH:10]=[CH:9][C:7]=2[N:8]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 735777(1R,2R)-2-Aminocyclohexanol2×HCID 86681056HCID 86681056, compoundHCID 86681057HCID 86681057, compound

Product 1

HCID 71550846HCID 71550846, compound

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

A 2:1 mixture of methyl 3-((2-(methylsulfinyl)benzo[d]thiazol-6-yl)methyl)-3H-imidazo[4,5-b]pyridine-6-carboxylate and methyl 3-((2-(methylsulfonyl)benzo[d]thiazol-6-yl)methyl)-3H-imidazo[4,5-b]pyridine-6-carboxylate (360 mg) from Step 4 of this Example was dissolved in anhydrous DMA (10 mL), and (1R,2R)-(−)-2-aminocyclohexanol (322 mg, 2.79 mmol) and DIEA (360 mg, 2.79 mmol) were added. The reaction vessel was sealed and the mixture was heated with stirring at 100° C. for 19 h. LCMS indicated the reaction was not complete. To the reaction mixture was added additional (1R,2R)-(−)-2-aminocyclohexanol (100 mg, 0.870 mmol) and the reaction vessel was sealed and the mixture was heated at 100° C. for a further 15 h. After the reaction mixture was cooled to rt, one half of the reaction 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 methyl 3-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]thiazol-6-yl)methyl)-3H-imidazo[4,5-b]pyridine-6-carboxylate (19 mg) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.96 (d, J=7.3 Hz, 1H), 8.76 (m, 1H), 8.54 (m, 1H), 7.99 (br s, 1H), 7.66 (d, J=7.2 Hz, 1H), 7.16-7.33 (m, 2H), 5.51 (br s, 2H), 4.76 (br s, 1H), 3.89 (s, 3H), 3.30-3.50 (m, 2H), 2.02 (m, 1H), 1.86 (m, 1H), 1.50-1.70 (m, 2H), 1.10-1.30 (m, 4H). LCMS (ESI) m/z 438 (M+H)+.

Workup

  1. customThe reaction vessel was sealed
  2. temperaturethe mixture was heated
  3. customthe reaction vessel was sealed
  4. temperaturethe mixture was heated at 100° C. for a further 15 h
  5. temperatureAfter the reaction mixture was cooled to rt
  6. customone half of the reaction mixture was purified directly by reverse-phase
  7. 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-57f1b16f776d44539763f4d4a5575502
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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