Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → HCID 67264268, compound

HRID 1040916Notes

Reaction equation

HRID 1040916 reaction equation
[NH2:1][C:2]1[C:19]([O:20][CH3:21])=[CH:18][C:5]2[CH2:6][CH2:7][N:8]([CH2:11][C@H:12]([OH:17])[C:13]([F:16])([F:15])[F:14])[CH2:9][CH2:10][C:4]=2[CH:3]=1.Cl[C:23]1[N:28]=[C:27]([NH:29][C:30]2[CH:35]=[CH:34][C:33]([N:36]3[CH2:41][CH2:40][O:39][CH2:38][CH2:37]3)=[CH:32][C:31]=2[O:42][CH3:43])[C:26]([Cl:44])=[CH:25][N:24]=1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.C(=O)(O)[O-].[Na+]>>[Cl:44][C:26]1[C:27]([NH:29][C:30]2[CH:35]=[CH:34][C:33]([N:36]3[CH2:37][CH2:38][O:39][CH2:40][CH2:41]3)=[CH:32][C:31]=2[O:42][CH3:43])=[N:28][C:23]([NH:1][C:2]2[C:19]([O:20][CH3:21])=[CH:18][C:5]3[CH2:6][CH2:7][N:8]([CH2:11][C@H:12]([OH:17])[C:13]([F:14])([F:15])[F:16])[CH2:9][CH2:10][C:4]=3[CH:3]=2)=[N:24][CH:25]=1

Participants

5

Reactant 4

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 516892Sodium BicarbonateHCID 67263894HCID 67263894, compoundHCID 86633851(2,5-Dichloropyrimidin-4-yl)-(2-methoxy-4-morpholin-4-yl-phenyl)-amine

Product 1

HCID 67264268HCID 67264268, compoundYield 36%

Procedure

(S)-3-(7-Amino-8-methoxy-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-1,1,1-trifluoro-propan-2-ol (88 mg, 0.29 mmol), (2,5-Dichloro-pyrimidin-4-yl)-(2-methoxy-4-morpholin-4-yl-phenyl)-amine (0.104 g, 0.292 mmol), and 10-Camphorsulfonic acid (0.10 g, 0.43 mmol) were heated in a microwave vial at 120° C. for a total of 5 h then for 1.5 h at 140° C. The dark brown solution was added to a stirred satd. sodium bicarbonate solution (15 mL), stirred for 5 min then the supernatant was removed and the solids were stirred with 10 mL water. These solids were purified by RP-HPLC (10-30% acetonitrile:water) followed by formation of the free base with Macroporous carbonate resin to afford (S)-3-{7-[5-Chloro-4-(2-methoxy-4-morpholin-4-yl-phenylamino)-pyrimidin-2-ylamino]-8-methoxy-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl}-1,1,1-trifluoro-propan-2-ol as yellow solids (64 mg, 36%). m.p.=95-102° C.; LCMS (m/e) 624 (M+1); 1H-NMR (CD3OD, 400 MHz) δ 7.93 (m, 2H), 7.69 (d, 1H, J=8.7 Hz), 6.81 (s, 1H), 6.69 (s, 1H), 6.55 (m, 1H), 4.68 (m, 1H), 3.85 (m, 10H), 3.3-3.5 (m, 6H), 3.20 (m, 4H), 3.10 (m, 2H), 2.85 (m, 2H).

Workup

  1. additionThe dark brown solution was added to a stirred satd
  2. customthe supernatant was removed
  3. customThese solids were purified by RP-HPLC (10-30% acetonitrile:water)

Sources & evidence

ORD record
ord-45464aed532246dea99ea584957e9b84
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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