Ammonia → HCID 72705236, compound

HRID 1468089Notes

Reaction equation

HRID 1468089 reaction equation
N.[F:2][C:3]1[CH:4]=[C:5]2[C:36](=[CH:37][C:38]=1[O:39][CH2:40][CH2:41][CH2:42][F:43])[C:15]1([N:19]=[C:18]([N:20](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)[C:17]([CH3:35])=[N:16]1)[C:7]1([CH2:12][CH2:11][CH:10]([O:13][CH3:14])[CH2:9][CH2:8]1)[CH2:6]2>C1(C)C=CC=CC=1>[F:2][C:3]1[CH:4]=[C:5]2[C:36](=[CH:37][C:38]=1[O:39][CH2:40][CH2:41][CH2:42][F:43])[C:15]1([N:19]=[C:18]([NH2:20])[C:17]([CH3:35])=[N:16]1)[C:7]1([CH2:8][CH2:9][CH:10]([O:13][CH3:14])[CH2:11][CH2:12]1)[CH2:6]2

Participants

4

Reactant 2

HCID 222AmmoniaHCID 86706699HCID 86706699, compound2×

Product 1

HCID 72705236HCID 72705236, compoundYield 10%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
85 °C

Procedure

Methanolic ammonia (7 M, 1.89 mL, 13.2 mmol) and toluene (2 mL) was added to di-tert-butyl [5′-fluoro-6′-(3-fluoropropoxy)-4-methoxy-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazol]-4″-yl]imidodicarbonate (Intermediate 16, 260 mg, 0.44 mmol). The mixture was transferred to a MW vial which was capped and heated to 85° C. for a week. The mixture was concentrated and partitioned between EtOAc and 2 M citric acid. The phases were separated and the organic phase was discarded. The aqueous phase was basified by addition of 50% aq. NaOH solution to pH 12 and then extracted with EtOAc. The combined organic phases were treated with charcoal, filtered through diatomaceous earth and concentrated. Purification of the residue by preparative HPLC afforded the title compound (17 mg, 10% yield). 1H NMR (500 MHz, DMSO-d6) δ ppm 0.83-0.95 (m, 1 H) 1.07-1.26 (m, 2 H) 1.33-1.49 (m, 3 H) 1.76-1.85 (m, 2 H) 1.97-2.11 (m, 2 H) 2.13-2.19 (m, 3 H) 2.82-2.99 (m, 3 H) 3.18 (s, 3 H) 3.90-4.01 (m, 2 H) 4.51 (t, 1 H) 4.61 (t, 1 H) 6.26 (d, 1 H) 6.53 (s, 2 H) 7.13 (d, 1 H); MS (ES+) m/z 392 [M+H]+.

Workup

  1. customwas capped
  2. concentrationThe mixture was concentrated
  3. custompartitioned between EtOAc and 2 M citric acid
  4. customThe phases were separated
  5. additionThe aqueous phase was basified by addition of 50% aq. NaOH solution to pH 12
  6. extractionextracted with EtOAc
  7. additionThe combined organic phases were treated with charcoal
  8. filtrationfiltered through diatomaceous earth
  9. concentrationconcentrated
  10. customPurification of the residue by preparative HPLC

Sources & evidence

ORD record
ord-be7add5dc50143d29aaf6034c330211e
Source dataset
uspto-grants-2015_04
Patent number
US09000183B2

Reaction notes

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