Water → tert-Butyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-chloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate

HRID 2092864Notes

Reaction equation

HRID 2092864 reaction equation
[Cl:1][C:2]1[C:7]2[C:8](=[O:18])[N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:10][C:6]=2[C:5]([F:19])=[C:4](Cl)[N:3]=1.[NH2:21][C@@H:22]1[CH2:27][CH2:26][CH2:25][CH2:24][C@@H:23]1[NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32].CCN(C(C)C)C(C)C.O>CC(O)C.CS(C)=O>[C:31]([O:30][C:29]([NH:28][C@H:23]1[CH2:24][CH2:25][CH2:26][CH2:27][C@H:22]1[NH:21][C:4]1[N:3]=[C:2]([Cl:1])[C:7]2[C:8](=[O:18])[N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:10][C:6]=2[C:5]=1[F:19])=[O:35])([CH3:34])([CH3:32])[CH3:33]

Participants

7

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protectedHCID 86654739tert-Butyl 4,6-dichloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate

Product 1

HCID 86654740tert-Butyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-chloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylateYield 49.1%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred suspension of tert-butyl 4,6-dichloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate (12.5 g, 38.9 mmol) in 2-propanol (72 mL) was added a solution of tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (10.01 g, 46.7 mmol) in DMSO (12.00 mL) and DIPEA (8.84 mL, 50.6 mmol). The reaction mixture was heated to 90° C. for 16 h at which point it was cooled to 50° C. and water (50 mL) was added dropwise to give a precipitate. The suspension was stirred at 50° C. for 1 h then cooled to RT. The suspension was reheated to 50° C. for 15 min and cooled to RT for two more cycles. The solids were subsequently filtered and washed with isopropanol (20 mL) and dried on a filter to give the title compound (9.538 g, 49%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.18-1.76 (br m, 26H), 3.83 (br s, 1H), 4.12 (br s, 1H), 4.72 (s, 2H), 6.71 (d, J=7.58 Hz, 1H), 7.22 (d, J=6.32 Hz, 1H).

Workup

  1. temperaturewas cooled to 50° C.
  2. customto give a precipitate
  3. temperaturethen cooled to RT
  4. waitThe suspension was reheated to 50° C. for 15 min
  5. temperaturecooled to RT for two more cycles
  6. filtrationThe solids were subsequently filtered
  7. washwashed with isopropanol (20 mL)
  8. customdried on
  9. filtrationa filter

Sources & evidence

ORD record
ord-870c1c9f97964b8b833545d4134c1cf5
Source dataset
uspto-grants-2013_05
Patent number
US08440689B2

Reaction notes

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