Dimethylformamide → HCID 86700248, compound

HRID 879440Notes

Reaction equation

HRID 879440 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:37]([CH3:38])=[CH:36][C:15]2[N:16]=[C:17]([C:19]3[CH:24]=[CH:23][N:22]=[C:21]([N:25]4[CH2:30][CH2:29][C:28]5[N:31]([CH3:35])[N:32]=[C:33]([CH3:34])[C:27]=5[CH2:26]4)[CH:20]=3)[S:18][C:14]=2[C:13]=1[C:39]1[CH:44]=[CH:43][C:42]([Cl:45])=[CH:41][CH:40]=1)[C:7]([O:9]CC)=[O:8])([CH3:4])([CH3:3])[CH3:2].CN1C2CCNCC=2C(C)=N1.[OH-].[Na+].CN(C=O)C>CO.C1COCC1.C(O)(=O)C>[C:1]([O:5][C@@H:6]([C:12]1[C:37]([CH3:38])=[CH:36][C:15]2[N:16]=[C:17]([C:19]3[CH:24]=[CH:23][N:22]=[C:21]([N:25]4[CH2:30][CH2:29][C:28]5[N:31]([CH3:35])[N:32]=[C:33]([CH3:34])[C:27]=5[CH2:26]4)[CH:20]=3)[S:18][C:14]=2[C:13]=1[C:39]1[CH:40]=[CH:41][C:42]([Cl:45])=[CH:43][CH:44]=1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 14798Sodium HydroxideHCID 82586427HCID 82586427, compoundHCID 86700247HCID 86700247, compound

Product 1

HCID 86700248HCID 86700248, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
45 °C

Procedure

A solution of (S)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-2-(2-(1,3-dimethyl-6,7-dihydro-1H-pyrazolo[4,3-c]pyridin-5(4H)-yl)pyridin-4-yl)-5-methylbenzo[d]thiazol-6-yl)acetate: A mixture of 1,3-dimethyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine (7.7 mg, 0.012 mmol) and 5M sodium hydroxide (47 μL, 0.24 mmol) in methanol (0.1 mL) and THF (0.5 mL) was heated 45° C. for 2 h. Acetic acid (1 drop) and DMF (0.3 mL) were added and mixture concentrated to ˜0.3 mL, diluted with methanol, filtered and purified by Gilson HPLC (Gemini, 5 to 100% ACN/H2O+0.1% TFA) to give product after lyophilization. LCMS-ESI+: calc'd for C32H34ClN5O3S: 616.2 (M+H+); Found: 616.3 (M+H+); 1H NMR (400 MHz, CD3OD) δ 8.11 (d, J=6.3 Hz, 1H), 7.96 (s, 1H), 7.83 (s, 1H), 7.68 (dd, J=8.5, 1.7 Hz, 1H), 7.67-7.54 (m, 3H), 7.47 (dd, J=6.3, 1.3 Hz, 1H), 5.27 (s, 1H), 4.63 (s, 2H), 4.07 (t, J=5.7 Hz, 2H), 3.72 (s, 3H), 2.93 (t, J=5.5 Hz, 2H), 2.64 (s, 3H), 2.24 (s, 3H), 0.97 (s, 9H).

Workup

  1. concentrationmixture concentrated to ˜0.3 mL
  2. additiondiluted with methanol
  3. filtrationfiltered
  4. custompurified by Gilson HPLC (Gemini, 5 to 100% ACN/H2O+0.1% TFA)
  5. customto give product after lyophilization

Sources & evidence

ORD record
ord-5ddcaeb0891a40cca8dc743f8e618ed4
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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