Ammonia → HCID 178457184, compound

HRID 1054533Notes

Reaction equation

HRID 1054533 reaction equation
Cl[C:2]1[C:3]2[CH:10]=[CH:9][N:8]([C@H:11]3[C@@H:15]4[O:16][C:17]([CH3:20])([CH3:19])[O:18][C@@H:14]4[CH:13]([CH2:21][N:22]([CH2:26][CH2:27][CH2:28][CH2:29][C:30]4[NH:34][C:33]5[CH:35]=[CH:36][C:37]([C:39]([CH3:42])([CH3:41])[CH3:40])=[CH:38][C:32]=5[N:31]=4)[CH:23]([CH3:25])[CH3:24])[CH2:12]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[NH3:43]>>[C:39]([C:37]1[CH:36]=[CH:35][C:33]2[NH:34][C:30]([CH2:29][CH2:28][CH2:27][CH2:26][N:22]([CH2:21][CH:13]3[C@H:14]4[O:18][C:17]([CH3:20])([CH3:19])[O:16][C@H:15]4[C@H:11]([N:8]4[C:4]5[N:5]=[CH:6][N:7]=[C:2]([NH2:43])[C:3]=5[CH:10]=[CH:9]4)[CH2:12]3)[CH:23]([CH3:25])[CH3:24])=[N:31][C:32]=2[CH:38]=1)([CH3:42])([CH3:41])[CH3:40]

Participants

3

Reactant 2

HCID 222AmmoniaHCID 178457183HCID 178457183, compound

Product 1

HCID 178457184HCID 178457184, compoundYield 67%

Procedure

A solution of {[(3aR,6R,6aS)-6-{4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-2,2-dimethyl-hexahydrocyclopenta[d][1,3]dioxol-4-yl]methyl}[4-(5-tert-butyl-1H-1,3-benzodiazol-2-yl)butyl]propan-2-ylamine, (120 mg, 0.2 mmol) in methanolic ammonia (7N, 10 ml) was heated to 80° C. in a glass walled sealed tube with stirring overnight. The reaction mixture was then concentrated in vacuo, re-treated with methanolic ammonia (7N, 10 ml) and the reaction was continued for a further 48 hrs. This was then absorbed onto silica gel and purified by silica gel column chromatography, eluting with 7N NH3 in MeOH:DCM (4:96). The product was purified further on a preparative TLC plate, eluting with 7N NH3 in MeOH:DCM (1:9) to give an off-white solid product (75 mg, 67%): MS (ESI+) for C33H47N7O2 m/z 573.79 [M+H]+; HPLC purity 98% (ret. time, 1.23 min); 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 7.92-8.29 (1H, m), 7.22-7.58 (2H, m), 6.58-7.08 (1H, m), 6.24-6.58 (1H, m), 4.68-5.00 (2H, m), 4.28-4.46 (2H, m), 3.21-3.33 (2H, m), 2.50-3.03 (4H, m), 2.36 (5H, d, J=5.34 Hz), 1.54-2.09 (3H, m), 1.32-1.49 (6H, m), 1.14-1.34 (9H, m), 0.71-1.01 (6H, m)

Workup

  1. customwalled sealed tube
  2. concentrationThe reaction mixture was then concentrated in vacuo
  3. additionre-treated with methanolic ammonia (7N, 10 ml)
  4. waitthe reaction was continued for a further 48 hrs
  5. customThis was then absorbed onto silica gel
  6. custompurified by silica gel column chromatography
  7. washeluting with 7N NH3 in MeOH:DCM (4:96)
  8. customThe product was purified further on a preparative TLC plate
  9. washeluting with 7N NH3 in MeOH:DCM (1:9)

Sources & evidence

ORD record
ord-03c689a3ef2547558d32822bec1d628c
Source dataset
uspto-grants-2016_07
Patent number
US09394310B2

Reaction notes

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